Affinage

GDF5

Growth/differentiation factor 5 · UniProt P43026

Length
501 aa
Mass
55.4 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GDF5 (CDMP1/BMP14) is a secreted BMP-family ligand that is necessary and sufficient for cartilage growth and for restricting joint formation to its correct positions in the developing skeleton (PMID:10208739). It acts at sequential stages of skeletal development, first promoting chondrogenic cell condensation through increased cell adhesion and then driving epiphyseal cell proliferation to set skeletal element size (PMID:11263662), and it lineage-marks the continuously recruited interzone cells that build joint compartments and entheseal fibrocartilage (PMID:27292641, PMID:26141957). GDF5 signals principally through the type I receptor BMPR1B (ALK6) to activate canonical Smad1/5/8 phosphorylation and downstream targets such as ID1/ID3 and Trps1, while also engaging BMPR1A, BMPR2 and Smad-independent (p38, non-Smad) routes (PMID:10631181, PMID:16716349, PMID:18363966); its output is further shaped by a ligand-independent BMPR1B–Ror2 heteromeric complex that tunes chondrogenic differentiation (PMID:15569154). Ligand activity is held in check by the antagonist Noggin, which blocks GDF5 effects in vivo (PMID:9918693), and by DAN-family antagonist Gremlin-2, whose crystal structure with GDF5 reveals an H-shaped assembly that occludes both type I and type II receptor motifs (PMID:27524626). Disease-causing mutations partition cleanly by mechanism: substitutions that abolish or remodel receptor-binding specificity cause brachydactyly and symphalangism (e.g. L441P loss of BMPR1A/B binding; R438L gain of BMPR1A binding) (PMID:16127465), residues at the Noggin interface (N445, W414, S94) confer antagonist resistance producing synostosis or gain-of-function chondrogenesis (PMID:19956691, PMID:21976273, PMID:24098149), and dominant-negative alleles that disrupt secretion or signaling cause brachydactyly, ankylosis and early osteoarthritis (PMID:9288098, PMID:17656374). GDF5 expression is governed by a >100 kb array of modular tissue-specific enhancers, including the GROW1 long-bone enhancer carrying a positively selected human variant (PMID:27902701, PMID:28671685), and is fine-tuned at the 5'-UTR by CpG methylation and by trans-acting repressors (Sp1, Sp3, DEAF-1) and activators (YY1, SOX11), with the osteoarthritis-risk rs143383 T allele lowering joint-wide GDF5 expression (PMID:19565498, PMID:23825960, PMID:22929025, PMID:23356643, PMID:24861163). Beyond the skeleton, GDF5 suppresses cartilage catabolism by inducing DKK1-mediated inhibition of canonical Wnt signaling (PMID:24561281), drives tenogenic differentiation via a Sirt1-JNK/Smad1-PPARγ axis (PMID:30116367), and stabilizes XIAP through BMPR2 to confer Smad-independent anti-apoptotic protection (PMID:19782107).

Mechanistic history

Synthesis pass · year-by-year structured walk · 34 steps
  1. 1997 Medium

    Established that GDF5 must be secreted as an active dimer to function and that a cysteine-disrupting mutation acts dominant-negatively, hinting that GDF5 can heterodimerize with related BMP ligands.

    Evidence In vitro secretion and activity assays with dominant-negative analysis in cell culture

    PMID:9288098

    Open questions at the time
    • Heterodimer formation proposed but not biochemically reconstituted
    • Receptor engagement not addressed
  2. 1999 High

    Defined GDF5 as both necessary and sufficient for cartilage growth and for positioning joints, placing it at the center of skeletal patterning.

    Evidence Recombinant protein bead implantation in chick/mouse limbs plus brachypodism mutant genetics

    PMID:10208739

    Open questions at the time
    • Receptor and intracellular signaling not yet defined
    • Did not separate proliferative from condensation effects
  3. 1999 Medium

    Showed GDF5 activity is extracellularly antagonized by Noggin and that GDF5 expression is itself patterned by BMP7 and Hedgehog inputs.

    Evidence In vivo chick Noggin bead implantation, in situ hybridization, retroviral misexpression

    PMID:9918693

    Open questions at the time
    • Noggin binding interface on GDF5 not mapped
    • Direct vs indirect BMP7 regulation unresolved
  4. 2000 High

    Identified BMPR1B (ALK6) as the physiological type I receptor for GDF5 in digit chondrogenesis while revealing BMPR1B-independent GDF5 actions.

    Evidence Gdf5 x BmprIB compound mutant genetic epistasis in mice

    PMID:10631181

    Open questions at the time
    • Identity of alternative type I receptors not pinned down
    • Downstream Smad effectors not directly traced
  5. 2001 Medium

    Resolved GDF5 into two temporally distinct skeletal functions: increasing cell adhesion during condensation and stimulating epiphyseal proliferation to set element size.

    Evidence RCAS overexpression in chick, S-phase autoradiography, micromass adhesion assays

    PMID:11263662

    Open questions at the time
    • Molecular basis of adhesion increase unknown
    • Receptor coupling to each stage not dissected
  6. 2003 Medium

    Distinguished GDF5 from BMP4 functionally, showing GDF5 expands prechondrogenic condensations and sustains Sox9 without driving lineage instruction or full maturation.

    Evidence Comparative limb bud micromass culture with recombinant proteins and marker analysis

    PMID:15048875

    Open questions at the time
    • Receptor-level basis of the functional divergence unclear
    • Single culture system
  7. 2004 High

    Revealed that a ligand-independent BMPR1B–Ror2 heteromeric complex modulates GDF5 signaling, balancing Smad inhibition against a Smad-independent pathway during chondrogenesis.

    Evidence Reciprocal Co-IP, domain deletions, phosphorylation/reporter assays, ATDC5, compound mutant mice

    PMID:15569154

    Open questions at the time
    • Identity of the Smad-independent effector not defined
    • Stoichiometry of the complex unknown
  8. 2003 Low

    Provided early evidence that GDF5 receptors are present on intervertebral disc cells and that recombinant GDF5 dimer is bioactive on disc tissue.

    Evidence Adenoviral GDF5 gene transfer, Western blot, proliferation assay in rabbit disc cells

    PMID:14669002

    Open questions at the time
    • Limited mechanistic depth and single lab
    • Signaling pathway not dissected
  9. 2005 High

    Mapped receptor-binding specificity determinants by showing brachydactyly and symphalangism mutations selectively abolish or acquire type I receptor binding while sparing Noggin binding.

    Evidence SPR binding to receptor ectodomains plus micromass and cell-based functional assays

    PMID:16127465

    Open questions at the time
    • Structural basis of specificity switch not crystallographically resolved here
    • In vivo recapitulation of human phenotypes limited
  10. 2006 Medium

    Confirmed GDF5 activates canonical Smad1/5/8 signaling through BMPR1b/BMPR2/ACTR2a inducing ID1/ID3 in a Smad-dependent, MAPK-independent manner, and added a chemotactic function.

    Evidence Receptor expression analysis, Smad1 siRNA, ID reporters, MAPK inhibitors, chemotaxis in HUVSMC

    PMID:16716349

    Open questions at the time
    • Vascular smooth muscle context only
    • Chemotaxis mechanism partially defined
  11. 2007 Medium

    Showed a secretion-competent, normally dimerizing GDF5 mutation (W408R) acts dominant-negatively in vivo, causing brachypodism, ankylosis and early osteoarthritis.

    Evidence ENU mutagenesis mouse model with dominant-negative functional validation

    PMID:17656374

    Open questions at the time
    • Molecular interference mechanism not biochemically defined
    • Single lab
  12. 2008 Medium

    Placed Trps1 downstream of GDF5/ALK6–p38 signaling as a driver of chondrocyte differentiation and as a negative feedback repressor of Gdf5.

    Evidence GDF5 treatment of ATDC5, dn-Alk6, p38 inhibitor, Trps1 gain/loss-of-function

    PMID:18363966

    Open questions at the time
    • In vivo relevance of Trps1 feedback not tested
    • Single cell line
  13. 2009 Medium

    Defined a Smad/MAPK-independent anti-apoptotic mechanism in which GDF5 promotes BMPR2–XIAP interaction, stabilizing XIAP to inactivate caspases.

    Evidence Apoptosis, Co-IP, ubiquitination and caspase assays in MEFs vs SMCs

    PMID:19782107

    Open questions at the time
    • Cell-type specificity unexplained
    • Physiological context beyond cultured fibroblasts unclear
  14. 2009 Medium

    Demonstrated the osteoarthritis-risk rs143383 T allele lowers GDF5 expression joint-wide and that DEAF-1 binds the variant differentially, establishing a cis/trans regulatory disease axis.

    Evidence Allelic expression imbalance in patient tissue, luciferase reporters, EMSA

    PMID:19565498

    Open questions at the time
    • Full trans-factor repertoire not yet defined
    • Causal chain to cartilage degeneration not proven
  15. 2008 High

    Identified N445 as a Noggin-sensitivity determinant, showing synostosis mutations confer Noggin resistance and gain of chondrogenic function.

    Evidence Patient mutations, chick micromass and in vivo cartilage induction, structural sequence comparison

    PMID:19956691

    Open questions at the time
    • Crystallographic definition of the antagonist interface awaited
    • Additional residues only inferred from BMP9 swaps
  16. 2011 Medium

    Showed DNA methylation of the GDF5 5'-UTR modulates expression and that allele-created CpG sites couple epigenetic state to the rs143383 genetic effect.

    Evidence Bisulfite analysis, demethylating agent treatment, allelic expression quantification

    PMID:21642387

    Open questions at the time
    • Enzymes setting methylation marks not identified
    • Causal directionality in OA tissue unproven
  17. 2012 High

    Showed a single S94N mutation causing reduced BMPR2 binding paradoxically enhances chondrogenesis by escaping Noggin, illustrating coupled receptor and antagonist interfaces.

    Evidence SPR binding, reporter, ALP, qPCR, ATDC5 and mouse micromass assays

    PMID:21976273

    Open questions at the time
    • In vivo phenotype of S94N not established
    • Context-dependence across cell types only partly explored
  18. 2012 Medium

    Identified YY1 as a trans-activator binding a -41 bp promoter variant that can compensate for the OA-risk rs143383 T allele.

    Evidence Luciferase reporter, EMSA, YY1 siRNA knockdown

    PMID:22929025

    Open questions at the time
    • In vivo contribution of YY1 to joint GDF5 not shown
    • Interaction with repressors not modeled
  19. 2013 High

    Resolved the trans-acting regulatory network at rs143383, identifying Sp1/Sp3/DEAF-1 as repressors with allele-selective DEAF-1 activity contributing to differential expression.

    Evidence EMSA, oligo pulldown mass spectrometry, ChIP, RNAi, overexpression

    PMID:23825960

    Open questions at the time
    • Combinatorial logic with activators not fully integrated
    • Tissue specificity of factor occupancy not mapped
  20. 2013 Medium

    Identified SOX11 as a direct activator of GDF5 via conserved 5'-UTR SOX sites, enhancing but not ectopically inducing expression.

    Evidence SOX11 overexpression in vitro and in chick micromass/limb, binding site analysis

    PMID:23356643

    Open questions at the time
    • Requirement of SOX11 for endogenous Gdf5 not demonstrated by loss-of-function
    • Single lab
  21. 2013 Medium

    Defined a chondroprotective output: GDF5 suppresses catabolic MMP13/ADAMTS4 and raises anabolic ACAN/SOX9 via DKK1/FRZB-mediated inhibition of canonical Wnt signaling.

    Evidence Human chondrocyte pellet culture, qPCR/ELISA, Wnt agonists and DKK1 inhibitor

    PMID:24561281

    Open questions at the time
    • In vivo validation of the GDF5-DKK1-Wnt axis lacking
    • Receptor route to DKK1 induction not traced
  22. 2013 Low

    Provided initial evidence that GDF5 induces neurite outgrowth in human neuronal cells through direct BMP type I receptor–Smad1/5/8 signaling.

    Evidence SH-SY5Y culture, Smad1/5/8 phosphorylation and receptor activation assays

    PMID:23831389

    Open questions at the time
    • Pathway dissection limited and not confirmed by inhibitors in detail
    • Single cell line, single lab
  23. 2013 High

    Showed a single W414R mutation produces simultaneous gain (Noggin insensitivity, SYNS2) and loss (reduced BMPR1A signaling, BDA1) of function, unifying two disease mechanisms in one residue.

    Evidence Mesenchymal chondrogenesis assay, luciferase reporter, SPR binding

    PMID:24098149

    Open questions at the time
    • Structural basis of dual effect not crystallized here
    • In vivo dual phenotype recapitulation not shown
  24. 2014 Medium

    Linked epigenetics to allelic regulation by showing methylation at the +37 SP1/SP3 site attenuates repression and that joint-specific demethylation may underlie knee-selective OA association.

    Evidence Bisulfite sequencing of OA cartilage, methylation-sensitive EMSA, methylated reporter assays

    PMID:24861163

    Open questions at the time
    • Mechanism of joint-specific demethylation unknown
    • Causality vs correlation in OA not resolved
  25. 2015 High

    Showed GDF5+ enthesis progenitors give rise to fibrocartilage that mineralizes through Hedgehog signaling, extending GDF5 lineage roles to tendon-bone attachment.

    Evidence Gdf5-Cre lineage tracing with Smoothened conditional knockout

    PMID:26141957

    Open questions at the time
    • Role of GDF5 ligand itself (vs lineage marker) in enthesis not isolated
    • Hh-GDF5 crosstalk not defined
  26. 2015 Medium

    Demonstrated GDF5 can act as a context-dependent BMP2 antagonist even through BMPR-IA, implying an unidentified GDF5-specific co-receptor shapes signaling output.

    Evidence ALP assays in ATDC5/C2C12, heterotopic implantation, crystal structures of GDF5 R57A:BMPR-IA

    PMID:26385096

    Open questions at the time
    • The proposed co-receptor was not identified
    • Antagonism mechanism inferred rather than reconstituted
  27. 2015 Low

    Showed GDF5 synergizes with TGF-β1 to differentiate human adipose stromal cells toward nucleus pulposus cells, with Smad2/3 controlling identity and Smad1/5/8 controlling morphology.

    Evidence hASC culture, gene/ECM analysis, in vivo transplant, Smad pathway analysis

    PMID:26661057

    Open questions at the time
    • Pathway attribution lacked specific inhibitor confirmation
    • Single lab
  28. 2016 High

    Provided lineage-tracing evidence that joints are built by continuous influx of Gdf5+ interzone cells rather than a fixed early progenitor pool.

    Evidence Gdf5-CreERT2 knockin inducible lineage tracing at multiple timepoints

    PMID:27292641

    Open questions at the time
    • Signals directing lineage divergence into joint tissues unknown
    • Molecular heterogeneity of influxing cells uncharacterized
  29. 2016 High

    Determined the Gremlin-2:GDF5 crystal structure, showing an H-shaped assembly in which DAN-family antagonists occlude both type I and type II receptor motifs, distinct from Noggin's mode.

    Evidence X-ray crystallography at 2.9 Å with binding validation

    PMID:27524626

    Open questions at the time
    • Functional consequence of Grem2-GDF5 aggregates in vivo unknown
    • Selectivity of DAN family for GDF5 vs other BMPs not fully mapped
  30. 2016 High

    Mapped a >100 kb array of modular enhancers controlling Gdf5 expression in distinct joint subsets, explaining its spatially precise skeletal deployment.

    Evidence Transgenic enhancer reporters and functional rescue in Gdf5 mutant mice

    PMID:27902701

    Open questions at the time
    • Specific transcription factors at each enhancer only predicted
    • Enhancer-promoter looping architecture not defined
  31. 2017 High

    Identified the GROW1 long-bone enhancer regulating Gdf5 at growing bone ends, with a positively selected human variant that lowers enhancer activity, linking GDF5 regulation to human skeletal evolution.

    Evidence Transgenic enhancer assays, in vivo GROW1 deletion, human variant reporters, population genetics

    PMID:28671685

    Open questions at the time
    • Molecular consequence of the variant on bone length in humans not directly measured
    • Trans-factors at GROW1 unidentified
  32. 2018 Medium

    Defined a BMP14/GDF5-Sirt1-JNK/Smad1-PPARγ pathway driving tenogenic differentiation of mesenchymal stem cells.

    Evidence BMSC treatment, Sirt1 gain/loss, JNK/Smad inhibitors, acetylation assays

    PMID:30116367

    Open questions at the time
    • In vivo tendon repair relevance not established
    • Receptor route to JNK/Smad1 activation not defined
  33. 2019 Medium

    Placed GDF5 downstream of an embryonic CaVβ1 isoform in denervated muscle, linking GDF5 induction to muscle mass maintenance during aging.

    Evidence CaVβ1E gain/loss-of-function mouse models, denervation, GDF5 expression measurement

    PMID:31694926

    Open questions at the time
    • Direct GDF5 signaling effectors in muscle not defined
    • Causal sufficiency of GDF5 for muscle phenotype not isolated
  34. 2020 Medium

    Showed Gdf5 is upregulated in articular cartilage after osteoarthritis and injury through a downstream regulatory sequence and is repressed by YAP, tying GDF5 to injury-responsive repair signaling.

    Evidence Gdf5-LacZ reporter mice, DMM and acute injury models, YAP overexpression, human OA microarray

    PMID:31932746

    Open questions at the time
    • Mechanism coupling YAP to the regulatory sequence unknown
    • Functional benefit of injury-induced GDF5 not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the GDF5-specific co-receptor inferred from context-dependent BMP2 antagonism, and the unifying structural rules linking receptor-binding and Noggin-binding interfaces across GDF5 disease mutations, remain unresolved.
  • No co-receptor molecularly identified
  • No single structural framework reconciles overlapping receptor/antagonist interfaces
  • Causal in vivo link from cis-regulatory variants to osteoarthritis progression unproven

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4
Partners
BMPR1ABMPR1BBMPR2GREM2NOGROR2XIAP

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 A point mutation in CDMP1/GDF5 substituting the first conserved cysteine in the mature active domain produces a protein that is not secreted and is inactive in vitro; it exerts a dominant-negative effect by preventing secretion of other related BMP family members, proposed to occur through heterodimer formation. In vitro secretion assay, functional activity assay, dominant-negative analysis in cell culture Nature genetics Medium 9288098
1999 GDF5 is necessary and sufficient for cartilage development and restriction of joint formation to appropriate locations in the digits; recombinant GDF5 protein applied to developing chick and mouse limbs promotes cartilage growth and defines joint-forming boundaries, linking cartilage and joint development. Recombinant protein bead implantation in chick and mouse limb buds; genetic analysis of brachypodism mutants; in vivo loss-of-function and gain-of-function Developmental biology High 10208739
1999 The BMP antagonist Noggin binds to GDF5 and inhibits all observed effects of GDF5 in vivo (cartilage growth, digit morphogenesis); BMP-7 negatively regulates Gdf5 gene expression in joint-forming regions; Noggin treatment induces ectopic Gdf5 expression in interdigital mesoderm. In vivo chick bead implantation with Noggin; in situ hybridization; retroviral misexpression of Hedgehog signals Developmental biology Medium 9918693
2000 BMPR1B (ALK6) is the physiological type I receptor transducing GDF5 signal for digit cartilage formation; GDF5 acts through both BMPR1B-dependent and -independent processes; epistasis analysis shows BMPR1B regulates chondrogenesis and segmentation partly through GDF5 and partly independently, and GDF5 can signal through type I receptors other than BMPR1B. Mouse insertional mutant (BmprIB regulatory allele), double mutant genetic epistasis (Gdf5 x BmprIB), expression analysis Development (Cambridge, England) High 10631181
2001 GDF5 acts at two stages of skeletal development: first it promotes chondrogenic cell condensation by increasing cell adhesion; second, it increases skeletal element size by stimulating cell proliferation in epiphyseal cartilage. Retroviral overexpression of GDF5 in chick limb increased element size and S-phase cells; in vitro micromass cultures showed increased cell adhesiveness. Retroviral overexpression (RCAS) in chick embryo, autoradiography (S-phase labeling), micromass and single-cell suspension cultures of limb mesenchyme The Journal of bone and joint surgery. American volume Medium 11263662
2003 Members of the GDF5/6/7 subgroup are expressed in distinct subsets of developing joints and are required for joint, ligament, and cartilage formation at different skeletal sites; Gdf5 and Gdf6 double mutants show additive/synergistic defects, establishing functional redundancy and distinct spatial roles within the subgroup. Single and double null mouse mutant analysis, skeletal phenotyping Developmental biology High 12606286
2004 Ror2 (tyrosine kinase receptor) and BMPR1B (BRI-b, serine/threonine kinase receptor) form a ligand-independent heteromeric complex; the frizzled-like CRD domain of Ror2 is required for this complex; within the complex Ror2 is transphosphorylated by BMPR1B; Ror2 modulates GDF5 signaling by inhibiting Smad1/5 signaling and activating a Smad-independent pathway, both required for chondrogenic differentiation. Epistatic interactions in Ror2, BMPR1B, and Gdf5 compound mutant mice confirm in vivo functional interaction. Co-immunoprecipitation, domain-deletion mutants, phosphorylation assays, Smad reporter assays, ATDC5 chondrogenesis assay, compound mutant mouse genetics Genes to cells : devoted to molecular & cellular mechanisms High 15569154
2004 GDF5 and BMP4 have distinct functions during chondrogenesis: GDF5 increases the number of prechondrogenic condensations and cartilaginous nodules without altering overall differentiation pattern, and causes sustained elevated Sox9 expression and only transient Col10 upregulation; BMP4 is instructive and induces mesenchymal cells toward the chondrogenic lineage with accelerated maturation. Mouse embryonic limb bud micromass culture with recombinant protein treatment, gene expression analysis, histology Journal of cellular biochemistry Medium 15048875
2005 GDF5 L441P mutation causes brachydactyly type A2 by abolishing binding to both BMPR1A and BMPR1B ectodomains (loss of function); GDF5 R438L mutation causes symphalangism by acquiring increased binding to BMPR1A (normally BMP2's receptor) while retaining normal BMPR1B binding — a gain of BMP2-like receptor-binding specificity; both mutants show normal Noggin binding. This identifies key receptor-binding specificity determinants in GDF5. Biosensor (SPR) interaction analyses with receptor ectodomains, recombinant protein expression, limb bud micromass culture, ATDC5 and C2C12 cell treatment The Journal of clinical investigation High 16127465
2006 GDF5 binds specifically to BMPR1b, BMPR2, and ACTR2a receptors; GDF5 induces phosphorylation of Smad1/5/8 and their nuclear translocation, upregulating ID1 and ID3 expression via a Smad-dependent, MAPK-independent pathway in human vascular smooth muscle cells; GDF5 also has chemotactic activity partially dependent on Smad1 and ID1. Receptor expression analysis, Smad phosphorylation assay, Smad1 siRNA knockdown, ID1/ID3 reporter/expression assays, p38/ERK inhibitors, chemotaxis assay in HUVSMC Journal of molecular and cellular cardiology Medium 16716349
2008 GDF5 N445K and N445T mutations found in multiple synostosis syndrome patients confer resistance to the BMP inhibitor Noggin and altered signaling, causing gain of chondrogenic function. Residue N445 is a key determinant of Noggin sensitivity; BMP9 and BMP10, which naturally have lysine at this position, are also insensitive to Noggin. Swapping two additional residues was required to render BMP9 Noggin-sensitive, demonstrating that this residue is part of the antagonist interface. Patient mutation identification, functional studies in chicken micromass culture, ectopic cartilage induction in chick in vivo, sequence and structural comparison PLoS genetics High 19956691
2009 GDF5 and BMP2 prevent apoptosis in mouse embryonic fibroblasts (but not smooth muscle cells) via BMPR2; both factors stimulate interaction of BMPR2 with XIAP, reducing XIAP ubiquitination and increasing XIAP protein stability, which then inactivates caspases. This anti-apoptotic mechanism is independent of Smad and MAPK signaling. Apoptosis assay, Co-IP of BMPR2 with XIAP, ubiquitination assay, caspase activity assay, in isolated MEFs and SMCs Biochimica et biophysica acta Medium 19782107
2008 GDF5 promotes chondrogenesis downstream of BMPR1B (ALK6)/Alk6 signaling; Trps1 protein levels and nuclear translocation are upregulated by GDF5 treatment in a dose-dependent manner via Alk6 and p38 MAPK signaling; Trps1 acts downstream of GDF5 to promote chondrocyte differentiation and apoptosis, and also suppresses Gdf5 expression in a negative feedback loop. GDF5 protein treatment of ATDC5 cells, dominant-negative Alk6 (dn-Alk6) inhibition, p38 MAPK inhibitor (SB203580), Trps1 overexpression and knockdown, Western blot, immunofluorescence Genes to cells : devoted to molecular & cellular mechanisms Medium 18363966
2009 The OA-risk T allele of rs143383 in the GDF5 5'-UTR mediates reduced GDF5 expression in all joint tissues tested (cartilage, synovium, ligament), demonstrating a joint-wide cis-regulatory effect; a second 3'-UTR polymorphism influences allelic expression of GDF5 independent of rs143383; DEAF-1 protein binds differentially to the two alleles of rs143383 (trans-acting factor). Allelic expression imbalance assay in patient tissue, luciferase reporter assay, electrophoretic mobility shift assay (EMSA) Arthritis and rheumatism Medium 19565498
2011 DNA methylation of the GDF5 promoter and 5'-UTR regulates GDF5 expression; demethylation correlates with increased GDF5 expression; the CpG sites created by the C alleles of rs143383 and rs143384 are variably methylated; demethylating agent treatment of a heterozygous cell line further increases allelic expression imbalance between C and T alleles, demonstrating epigenetic modulation of the rs143383 genetic effect. Bisulfite methylation analysis, demethylating agent (5-aza-2'-deoxycytidine) treatment, allelic expression quantification in cell lines and joint tissues Human molecular genetics Medium 21642387
2013 Sp1, Sp3, P15, and DEAF-1 are trans-acting factors that bind to the GDF5 5'-UTR at rs143383; Sp1, Sp3, and DEAF-1 are repressors of GDF5 expression; DEAF-1 preferentially represses the T allele of rs143383 relative to the C allele, contributing to differential allelic expression; Sp1 and DEAF-1 in combination show greatest repressive activity. Competition and supershift EMSA, oligonucleotide pulldown with quantitative mass spectrometry, chromatin immunoprecipitation (ChIP), RNA interference (siRNA knockdown), overexpression assays PLoS genetics High 23825960
2013 SOX11 directly activates GDF5 expression by binding to conserved SOX family binding sites in the GDF5 5'-UTR, as demonstrated by in vitro and micromass culture overexpression; SOX11 misexpression in developing chick limbs via RCAS virus enhances but does not ectopically induce Gdf5 expression. SOX11 overexpression in vitro and in micromass cultures, RCAS retroviral infection in chick limb, reporter/expression assays, binding site identification BMC developmental biology Medium 23356643
2013 GDF5 stimulation of human chondrocytes inhibits expression of catabolic enzymes MMP13 and ADAMTS4, and upregulates anabolic genes ACAN and SOX9; this is mediated through upregulation of Wnt inhibitors DKK1 and FRZB, and MMP13 inhibition is specifically dependent on DKK1 (blocking canonical Wnt signaling). Human chondrocyte pellet culture, qPCR, ELISA for protein levels, Wnt3a and CHIR-99021 stimulation, DKK1 inhibitor (WAY-262611) co-treatment Osteoarthritis and cartilage Medium 24561281
2014 CpG methylation at the +37 site (4 bp upstream of rs143383) within the SP1/SP3 binding site has an allele-specific effect: methylation at this site attenuates SP1, SP3, and DEAF-1 repression of GDF5 promoter activity, and modulates the level and direction of allelic imbalance at rs143383. OA knee cartilage shows greater demethylation at +37 compared with hip cartilage, potentially explaining the knee-specific OA association. Bisulfite sequencing of normal and OA cartilage, methylation-sensitive EMSA for SP1/SP3 binding, luciferase promoter reporter assays with methylated constructs Human genetics Medium 24861163
2012 YY1 is a trans-acting activator of GDF5: it differentially binds to the alleles of a -41 bp promoter variant (more avidly to the A allele), and YY1 knockdown significantly reduces GDF5 expression; the A allele at -41 bp compensates for reduced expression mediated by the T allele of rs143383, identifying a regulatory site that can be manipulated to modulate GDF5 expression. Luciferase reporter assay, EMSA, YY1 siRNA knockdown European journal of human genetics : EJHG Medium 22929025
2013 GDF5 and BMP2 induce neurite outgrowth in SH-SY5Y human neuronal cells via a direct neuronal mechanism (not indirect glial effect), dependent on BMP type I receptor activation of canonical Smad1/5/8 signaling. SH-SY5Y cell culture with GDF5 and BMP2, Smad1/5/8 phosphorylation assay, BMP receptor activation assay Molecular and cellular neurosciences Low 23831389
2015 GDF5 acts as a context-dependent BMP-2 antagonist: in C2C12 cells (but not ATDC5 cells), GDF5 and its BMPR-IA-binding variant GDF5 R57A antagonize BMP2-mediated ALP expression even when signaling occurs solely via BMPR-IA; this context-dependency suggests an additional unidentified GDF5-specific co-receptor modulates signaling output. ALP assay in ATDC5 and C2C12 cells, in vivo heterotopic implantation in mice, crystal structure comparison of GDF5 R57A:BMPR-IA and BMP2:BMPR-IA complexes BMC biology Medium 26385096
2016 The crystal structure of Gremlin-2 (a DAN-family BMP antagonist) bound to GDF5 at 2.9-Å resolution reveals two Grem2 dimers binding perpendicularly to each GDF5 monomer in an H-like structure; upon complex formation, the dynamic N-terminus of Grem2 undergoes significant conformational change to simultaneously interact with both type I and type II receptor motifs on GDF5. DAN-family members can interact with BMP-type I receptor complexes (unlike Noggin which outcompetes the type I receptor), and Grem2-GDF5 forms a stable aggregate-like structure in vitro. X-ray crystallography (2.9-Å resolution), binding studies (SPR/biochemical), structural comparison with unbound Grem2 Cell reports High 27524626
2016 Gdf5-positive interzone cells continuously influx into developing joints rather than arising from a single early set of progenitors; using a knockin Gdf5-CreERT2 mouse, early labeling of Gdf5+ cells failed to mark the entire joint, while multiple sequential Cre activation steps showed progressive contribution to various joint compartments; spatiotemporal differences in Gdf5 expression may instruct lineage divergence into different joint tissues. Gdf5-CreERT2 knockin mouse lineage tracing, inducible Cre activation at multiple time points, tdTomato reporter Cell reports High 27292641
2016 Separate modular enhancers distributed over >100 kb of the Gdf5 locus (including upstream and downstream regions) control expression in distinct joint subsets (axial vs. limb, proximal vs. distal, specific sub-joints like elbow); predicted transcription factor binding sites within these enhancers are required for expression in particular joints; functional rescue in mice confirmed large flanking regions are required for normal joint formation. Transgenic mouse enhancer reporter assays, systematic locus survey, functional rescue tests in Gdf5 mutant mice PLoS genetics High 27902701
2017 A novel growth enhancer (GROW1) downstream of Gdf5 controls expression at the growing ends of long bones (not joints); GROW1 is required for normal Gdf5 expression at bone ends and normal bone lengths in vivo; a common human base-pair change in GROW1 decreases enhancer activity; the derived allele colocalizes with signatures of positive selection in Neandertals, Denisovans, and non-African humans. Transgenic mouse enhancer assays, GROW1 deletion in vivo, human variant functional reporter assay, population genetics analysis Nature genetics High 28671685
2018 The embryonic CaVβ1 isoform (CaVβ1E) boosts GDF5 expression downstream of its induction by muscle denervation; CaVβ1E overexpression improves muscle mass wasting in aging mice by increasing GDF5 expression; loss of CaVβ1E in aged muscle is associated with attenuated GDF5-dependent response to denervation. CaVβ1E overexpression mouse model, sciatic denervation model, CaVβ1E knockout in aging, GDF5 expression measurement Science translational medicine Medium 31694926
2015 Gdf5 progenitors in the enthesis give rise to fibrocartilage cells that mineralize via hedgehog signaling; hedgehog (Hh) pathway is required for enthesis mineralization, as tissue-specific deletion of Smoothened (the obligate Hh transducer) in tendon/enthesis cells leads to significant reductions in mineralized fibrocartilage apposition. Gdf5-Cre lineage tracing, tissue-specific Smoothened conditional knockout, histology, immunohistochemistry Developmental biology High 26141957
2012 GDF5 W408R mutation (identified by ENU mutagenesis in mice) is secreted and dimerizes normally but inhibits wild-type GDF5 function in a dominant-negative fashion, causing brachypodism, ankylosis and early-onset osteoarthritis; the mutation resides in a highly conserved region of the active signaling domain. ENU mutagenesis screen, heterozygous/homozygous phenotypic analysis, dominant-negative functional assay Human molecular genetics Medium 17656374
2012 GDF5 S94N mutation (in the knuckle epitope/BMPRII interaction site) impairs binding to BMPRII, reducing Smad and non-Smad signaling and reducing chondrogenic differentiation of ATDC5 cells; paradoxically, the mutation strongly enhances chondrogenesis in mouse micromass cultures because of strongly reduced affinity for Noggin, resulting in gain of function by escaping Noggin inhibition. SPR quantitative binding assays, reporter gene assay, ALP assay, qPCR, ATDC5 cell differentiation assay, mouse micromass culture Journal of bone and mineral research High 21976273
2013 GDF5 W414R mutation simultaneously causes gain and loss of function: insensitivity to Noggin (gain of function, causing SYNS2) and reduced signaling specifically via BMPR1A (loss of function, causing BDA1). SPR analysis confirmed altered receptor and antagonist binding affinities for this single mutation. Primary mesenchymal cell chondrogenesis assay, luciferase reporter assay, Surface Plasmon Resonance (SPR) binding analysis PLoS genetics High 24098149
2018 BMP14/GDF5 induces tenogenic differentiation of bone marrow mesenchymal stem cells by upregulating scleraxis, tenomodulin, and Sirt1; BMP14 triggers JNK and Smad1 phosphorylation; Sirt1 deacetylates PPARγ to promote tenogenic differentiation; Sirt1 gain/loss-of-function promotes/inhibits tenogenic differentiation; JNK and Smad1 inhibition increased PPARγ acetylation and inhibited tenogenic markers, defining the BMP14-Sirt1-JNK/Smad1-PPARγ tenogenic differentiation pathway. BMSCs treated with BMP14, Sirt1 overexpression and knockdown, JNK and Smad inhibitors, acetylation assay, qPCR and Western blot Experimental and therapeutic medicine Medium 30116367
2020 Gdf5 expression is upregulated in articular cartilage following experimental OA (destabilization of medial meniscus) and after acute cartilage injury; expression in injured synovium inversely correlates with YAP (Yes-associated protein) expression; overexpression of YAP suppresses Gdf5 expression in chondroprogenitors in vitro; Gdf5 upregulation in both injury models requires regulatory sequence downstream of Gdf5 coding exons. Gdf5-LacZ reporter mouse, DMM experimental OA model, acute cartilage injury model, immunohistochemistry, YAP overexpression in vitro, microarray analysis of human OA cartilage Scientific reports Medium 31932746
2003 GDF5 intervertebral disc cells express BMPR1A, BMPR1B, and BMPR2 receptors relevant for GDF5 action; adenoviral GDF5 gene transfer produces two secreted forms consistent with activated GDF5 dimer and proform; overexpressed GDF5 is bioactive and promotes growth of rabbit disc cells. Adenoviral gene transfer, western blot (two GDF5 forms), ELISA, [3H]thymidine proliferation assay, receptor expression analysis Journal of molecular medicine (Berlin, Germany) Low 14669002
2015 TGF-β1 and GDF5 synergistically drive differentiation of human adipose stromal cells toward nucleus pulposus-like cells; the Smad2/3 pathway mainly governs acquisition of NP cell molecular identity while the Smad1/5/8 pathway controls NP cell morphology. hASC culture with growth factors, gene expression analysis, extracellular matrix assessment, in vivo transplantation in nude mice, Smad pathway analysis Stem cells (Dayton, Ohio) Low 26661057

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Common variants in the GDF5-UQCC region are associated with variation in human height. Nature genetics 315 18193045
1999 GDF5 coordinates bone and joint formation during digit development. Developmental biology 309 10208739
2003 Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes. Developmental biology 272 12606286
1997 Disruption of human limb morphogenesis by a dominant negative mutation in CDMP1. Nature genetics 271 9288098
2018 Circular RNA CDR1as regulates osteoblastic differentiation of periodontal ligament stem cells via the miR-7/GDF5/SMAD and p38 MAPK signaling pathway. Stem cell research & therapy 207 30170617
1999 Mechanical tension-stress induces expression of bone morphogenetic protein (BMP)-2 and BMP-4, but not BMP-6, BMP-7, and GDF-5 mRNA, during distraction osteogenesis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 201 10404008
2000 Combinatorial signaling through BMP receptor IB and GDF5: shaping of the distal mouse limb and the genetics of distal limb diversity. Development (Cambridge, England) 176 10631181
2005 Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. The Journal of clinical investigation 170 16127465
2007 An SNP in the 5'-UTR of GDF5 is associated with osteoarthritis susceptibility in Europeans and with in vivo differences in allelic expression in articular cartilage. Human molecular genetics 168 17616513
1999 Expression and function of Gdf-5 during digit skeletogenesis in the embryonic chick leg bud. Developmental biology 165 9918693
2009 Large-scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand. Arthritis and rheumatism 152 19479880
2001 Growth/differentiation factor-5 (GDF-5) and skeletal development. The Journal of bone and joint surgery. American volume 126 11263662
2016 Joint Development Involves a Continuous Influx of Gdf5-Positive Cells. Cell reports 119 27292641
2004 Distinct functions of BMP4 and GDF5 in the regulation of chondrogenesis. Journal of cellular biochemistry 116 15048875
2011 Tendon tissue engineering: adipose-derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems. Biomedical materials (Bristol, England) 114 21436509
2011 Expression of the osteoarthritis-associated gene GDF5 is modulated epigenetically by DNA methylation. Human molecular genetics 96 21642387
2007 BMP-14 gene therapy increases tendon tensile strength in a rat model of Achilles tendon injury. The Journal of bone and joint surgery. American volume 95 17545436
2009 Functional analysis of the osteoarthritis susceptibility-associated GDF5 regulatory polymorphism. Arthritis and rheumatism 92 19565498
2015 Gdf5 progenitors give rise to fibrocartilage cells that mineralize via hedgehog signaling to form the zonal enthesis. Developmental biology 91 26141957
2014 CpG methylation regulates allelic expression of GDF5 by modulating binding of SP1 and SP3 repressor proteins to the osteoarthritis susceptibility SNP rs143383. Human genetics 86 24861163
2006 GDF5 is a second locus for multiple-synostosis syndrome. American journal of human genetics 80 16532400
2004 Modulation of GDF5/BRI-b signalling through interaction with the tyrosine kinase receptor Ror2. Genes to cells : devoted to molecular & cellular mechanisms 80 15569154
2017 Ancient selection for derived alleles at a GDF5 enhancer influencing human growth and osteoarthritis risk. Nature genetics 79 28671685
2011 GDF5 single-nucleotide polymorphism rs143383 is associated with lumbar disc degeneration in Northern European women. Arthritis and rheumatism 79 21360499
2004 Repair of articular cartilage defects in rabbits using CDMP1 gene-transfected autologous mesenchymal cells derived from bone marrow. Rheumatology (Oxford, England) 79 15187242
2014 GDF5 reduces MMP13 expression in human chondrocytes via DKK1 mediated canonical Wnt signaling inhibition. Osteoarthritis and cartilage 78 24561281
2018 Heparin functionalization increases retention of TGF-β2 and GDF5 on biphasic silk fibroin scaffolds for tendon/ligament-to-bone tissue engineering. Acta biomaterialia 77 29550439
2009 Mutations in GDF5 reveal a key residue mediating BMP inhibition by NOGGIN. PLoS genetics 76 19956691
2019 3D-bioprinting a genetically inspired cartilage scaffold with GDF5-conjugated BMSC-laden hydrogel and polymer for cartilage repair. Theranostics 72 31660079
2015 TGF-β1 and GDF5 Act Synergistically to Drive the Differentiation of Human Adipose Stromal Cells toward Nucleus Pulposus-like Cells. Stem cells (Dayton, Ohio) 68 26661057
2008 Freeze-dried tendon allografts as tissue-engineering scaffolds for Gdf5 gene delivery. Molecular therapy : the journal of the American Society of Gene Therapy 66 18180771
2002 Mutation in the cartilage-derived morphogenetic protein-1 (CDMP1) gene in a kindred affected with fibular hypoplasia and complex brachydactyly (DuPan syndrome). Clinical genetics 65 12121354
2008 Association of the DVWA and GDF5 polymorphisms with osteoarthritis in UK populations. Annals of the rheumatic diseases 64 19054821
2020 Regulation of Gdf5 expression in joint remodelling, repair and osteoarthritis. Scientific reports 62 31932746
2016 Heads, Shoulders, Elbows, Knees, and Toes: Modular Gdf5 Enhancers Control Different Joints in the Vertebrate Skeleton. PLoS genetics 60 27902701
2010 Evidence of association between GDF5 polymorphisms and congenital dislocation of the hip in a Caucasian population. Osteoarthritis and cartilage 59 20633687
2013 Photo-cured hyaluronic acid-based hydrogels containing growth and differentiation factor 5 (GDF-5) for bone tissue regeneration. Bone 55 24291420
2007 A novel dominant-negative mutation in Gdf5 generated by ENU mutagenesis impairs joint formation and causes osteoarthritis in mice. Human molecular genetics 55 17656374
2013 The effect of a bioactive collagen membrane releasing PDGF or GDF-5 on bone regeneration. Biomaterials 53 24388383
2004 Brachydactyly type C caused by a homozygous missense mutation in the prodomain of CDMP1. American journal of medical genetics. Part A 52 14735582
2013 The identification of trans-acting factors that regulate the expression of GDF5 via the osteoarthritis susceptibility SNP rs143383. PLoS genetics 51 23825960
2003 Release of active and depot GDF-5 after adenovirus-mediated overexpression stimulates rabbit and human intervertebral disc cells. Journal of molecular medicine (Berlin, Germany) 51 14669002
2003 Broad phenotypic spectrum caused by an identical heterozygous CDMP-1 mutation in three unrelated families. American journal of medical genetics. Part A 50 12567410
2013 BMP2 and GDF5 induce neuronal differentiation through a Smad dependant pathway in a model of human midbrain dopaminergic neurons. Molecular and cellular neurosciences 47 23831389
2002 Frameshift mutation in the cartilage-derived morphogenetic protein 1 (CDMP1) gene and severe acromesomelic chondrodysplasia resembling Grebe-type chondrodysplasia. American journal of medical genetics 46 12124730
2019 Sustained release of GDF5 from a designed coacervate attenuates disc degeneration in a rat model. Acta biomaterialia 45 30660009
2008 Novel point mutations in GDF5 associated with two distinct limb malformations in Chinese: brachydactyly type C and proximal symphalangism. Journal of human genetics 45 18283415
2016 Structure of Gremlin-2 in Complex with GDF5 Gives Insight into DAN-Family-Mediated BMP Antagonism. Cell reports 42 27524626
2013 SOX11 contributes to the regulation of GDF5 in joint maintenance. BMC developmental biology 39 23356643
2008 Trps1 plays a pivotal role downstream of Gdf5 signaling in promoting chondrogenesis and apoptosis of ATDC5 cells. Genes to cells : devoted to molecular & cellular mechanisms 39 18363966
2015 GDF-5 can act as a context-dependent BMP-2 antagonist. BMC biology 37 26385096
2012 Genetic association analysis of GDF5 and ADAM12 for knee osteoarthritis. Joint bone spine 36 22284607
2006 Differential regulation of GDF-5 and FGF-2/4 by immobilisation in ovo exposes distinct roles in joint formation. Developmental dynamics : an official publication of the American Association of Anatomists 36 16425226
2012 A rare variant in the osteoarthritis-associated locus GDF5 is functional and reveals a site that can be manipulated to modulate GDF5 expression. European journal of human genetics : EJHG 35 22929025
2023 Skeletal Muscle-Derived Exosomal miR-146a-5p Inhibits Adipogenesis by Mediating Muscle-Fat Axis and Targeting GDF5-PPARγ Signaling. International journal of molecular sciences 34 36901991
2020 Long Noncoding RNA GAS5 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Regulating GDF5 and p38/JNK Signaling Pathway. Frontiers in pharmacology 34 32508644
2009 GDF5 and BMP2 inhibit apoptosis via activation of BMPR2 and subsequent stabilization of XIAP. Biochimica et biophysica acta 34 19782107
2006 Upregulation of ID protein by growth and differentiation factor 5 (GDF5) through a smad-dependent and MAPK-independent pathway in HUVSMC. Journal of molecular and cellular cardiology 34 16716349
2022 Regulatory Mechanisms of Prg4 and Gdf5 Expression in Articular Cartilage and Functions in Osteoarthritis. International journal of molecular sciences 33 35563063
2015 Regulation of α5 and αV Integrin Expression by GDF-5 and BMP-7 in Chondrocyte Differentiation and Osteoarthritis. PloS one 33 26010756
2013 A GDF5 point mutation strikes twice--causing BDA1 and SYNS2. PLoS genetics 33 24098149
2016 Inhibition of microRNA-34a prevents IL-1β-induced extracellular matrix degradation in nucleus pulposus by increasing GDF5 expression. Experimental biology and medicine (Maywood, N.J.) 32 27385596
2005 The role of growth/differentiation factor 5 (GDF5) in the induction and survival of midbrain dopaminergic neurones: relevance to Parkinson's disease treatment. Journal of anatomy 32 16185246
2019 microRNA-132 inhibits osteogenic differentiation of periodontal ligament stem cells via GDF5 and the NF-κB signaling pathway. Pathology, research and practice 30 31718857
2018 microRNA-665 promotes the proliferation and matrix degradation of nucleus pulposus through targeting GDF5 in intervertebral disc degeneration. Journal of cellular biochemistry 30 29761869
2018 Injured Achilles Tendons Treated with Adipose-Derived Stem Cells Transplantation and GDF-5. Cells 30 30200326
2010 Combined use of bFGF and GDF-5 enhances the healing of medial collateral ligament injury. Biochemical and biophysical research communications 30 20937261
2013 Analysis of association between IL-1β, CASP-9, and GDF5 variants and low-back pain in Chinese male soldier: clinical article. Journal of neurosurgery. Spine 29 23725396
2018 Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28 29146735
2018 Impact of broad regulatory regions on Gdf5 expression and function in knee development and susceptibility to osteoarthritis. Annals of the rheumatic diseases 28 29311146
2012 GDF5 regulates TGFß-dependent angiogenesis in breast carcinoma MCF-7 cells: in vitro and in vivo control by anti-TGFß peptides. PloS one 28 23226264
2006 A novel mutation in GDF5 causes autosomal dominant symphalangism in two Chinese families. American journal of medical genetics. Part A 28 16892395
2020 Knockout of miR-21-5p alleviates cartilage matrix degradation by targeting Gdf5 in temporomandibular joint osteoarthritis. Bone & joint research 27 33231490
2016 Adenovirus-mediated GDF-5 promotes the extracellular matrix expression in degenerative nucleus pulposus cells. Journal of Zhejiang University. Science. B 27 26739524
2012 New insights into the molecular mechanism of multiple synostoses syndrome (SYNS): mutation within the GDF5 knuckle epitope causes noggin-resistance. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 27 21976273
2009 A novel polymorphism of GDF5 gene and its association with body measurement traits in Bos taurus and Bos indicus breeds. Molecular biology reports 27 19590978
2008 A novel insertion mutation in the cartilage-derived morphogenetic protein-1 (CDMP1) gene underlies Grebe-type chondrodysplasia in a consanguineous Pakistani family. BMC medical genetics 27 19038017
2005 A mutation in the receptor binding site of GDF5 causes Mohr-Wriedt brachydactyly type A2. Journal of medical genetics 27 16014698
2024 Decellularized nucleus pulposus matrix/chitosan hybrid hydrogel combined with nucleus pulposus stem cells and GDF5-loaded microspheres for intervertebral disc degeneration prevention. Molecular medicine (Cambridge, Mass.) 26 38200442
2005 Du Pan syndrome phenotype caused by heterozygous pathogenic mutations in CDMP1 gene. American journal of medical genetics. Part A 26 16222676
2019 An embryonic CaVβ1 isoform promotes muscle mass maintenance via GDF5 signaling in adult mouse. Science translational medicine 25 31694926
2018 BMP14 induces tenogenic differentiation of bone marrow mesenchymal stem cells in vitro. Experimental and therapeutic medicine 25 30116367
2012 Positive selection on the osteoarthritis-risk and decreased-height associated variants at the GDF5 gene in East Asians. PloS one 24 22905146
2010 Mutations in GDF5 presenting as semidominant brachydactyly A1. Human mutation 24 20683927
2014 Association between GDF5 rs143383 polymorphism and knee osteoarthritis: an updated meta-analysis based on 23,995 subjects. BMC musculoskeletal disorders 23 25467786
2014 Growth and differentiation factor-5 (GDF-5) in the human intervertebral annulus cells and its modulation by IL-1ß and TNF-α in vitro. Experimental and molecular pathology 22 24582800
2013 Rs143383 in the growth differentiation factor 5 (GDF5) gene significantly associated with osteoarthritis (OA)-a comprehensive meta-analysis. International journal of medical sciences 22 23423687
2003 Correlation of GDF5 and connexin 43 mRNA expression during embryonic development. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology 22 14613311
2017 Novel homozygous sequence variants in the GDF5 gene underlie acromesomelic dysplasia type-grebe in consanguineous families. Congenital anomalies 21 27577507
2005 Variable hand and foot abnormalities in family with congenital vertical talus and CDMP-1 gene mutation. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20 16005596
2022 Long non-coding RNA SNHG5 promotes the osteogenic differentiation of bone marrow mesenchymal stem cells via the miR-212-3p/GDF5/SMAD pathway. Stem cell research & therapy 19 35346361
2019 DNA hypermethylation of GDF5 in developmental dysplasia of the hip (DDH). Molecular genetics & genomic medicine 18 31338995
2018 The role of Gdf5 regulatory regions in development of hip morphology. PloS one 18 30388100
2016 Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation. Scientific reports 18 27030100
2015 Association of GDF5, SMAD3 and RUNX2 polymorphisms with temporomandibular joint osteoarthritis in female Han Chinese. Journal of oral rehabilitation 18 25757091
2014 Human chondrocytes respond discordantly to the protein encoded by the osteoarthritis susceptibility gene GDF5. PloS one 18 24466161
2011 Deep sequencing of GDF5 reveals the absence of rare variants at this important osteoarthritis susceptibility locus. Osteoarthritis and cartilage 17 21281725
2001 Gdf5 is expressed in the developing skeleton of median fins of late-stage zebrafish, Danio rerio. Development genes and evolution 17 11862461
2021 Genetic Study of IL6, GDF5 and PAPPA2 in Association with Developmental Dysplasia of the Hip. Genes 16 34203285
2003 Grebe dysplasia and the spectrum of CDMP1 mutations. Pediatric pathology & molecular medicine 16 12687891

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