Affinage

Showing MSTN — GDF8 is a alias.

MSTN

Growth/differentiation factor 8 · UniProt O14793

Length
375 aa
Mass
42.8 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MSTN (GDF8/myostatin) is a secreted TGF-β superfamily ligand that acts as a dominant negative regulator of skeletal muscle mass, established by loss-of-function mutations that remove or disrupt its conserved TGF-β domain and produce the double-muscled phenotype in cattle and muscle hyperplasia across species (PMID:9314496, PMID:32098368). Myostatin circulates as a latent complex held inactive by its prodomain; release of the active dimer requires tolloid-family proteolysis at the scissile bond, which depends on prodomain residues Y94 and D92, and tolloid-resistant prodomain mutants act in a dominant-negative manner to suppress wild-type GDF8 (PMID:33876824). The mature ligand signals through type II activin receptors (ActRIIB) and the type I receptor ALK5/ALK4 to drive SMAD2/3-SMAD4 transcription, which underlies its anti-myogenic action: GDF8-SMAD2/3 represses myogenic differentiation, and loss of MSTN de-represses myogenesis by elevating the demethylase TET1 and demethylating PAX3, PAX7, MyoD, and MyoG promoters (PMID:32210722, PMID:33425488, PMID:33195207). In parallel to SMAD signaling, GDF8 activates p38 MAPK through TAK1 to inhibit proliferation and induce p21, and acts in part through IGFBP-3 to suppress myoblast proliferation (PMID:15567067, PMID:14502562). Beyond muscle, ALK5-SMAD2/3 signaling mediates pleiotropic roles: GDF8 suppresses osteoblast differentiation and promotes osteoclastogenesis, regulates fracture callus formation, drives trophoblast invasion via FSTL3 and MMP2 upregulation, and stimulates granulosa-cell aromatase and SERPINE1 expression (PMID:28074479, PMID:18852073, PMID:33195207, PMID:34432647, PMID:34239360, PMID:33425488). MSTN deletion engages AMPK-linked metabolic programs and attenuates cardiac hypertrophy through AMPK/mTOR and PPARγ/NF-κB pathways (PMID:31374285, PMID:31923740). Its activity is antagonized extracellularly by follistatin and by the WFIKKN2 follistatin domain, both of which block ActRIIB binding, and the closely related ligand GDF11 shares its receptors but is a more potent SMAD2/3 activator owing to differences in the type I receptor binding site (PMID:30814254, PMID:28257634, PMID:32071240). The receptor pharmacology is therapeutically tractable: ATP-competitive inhibitors of the receptor kinases and dual antibody blockade of GDF8 plus activin A increase muscle mass in vivo (PMID:25368322, PMID:40360507).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1997 High

    Establishing that myostatin is a negative regulator of muscle growth answered whether a single secreted factor could constrain muscle mass, anchoring the entire field.

    Evidence cDNA cloning and sequence analysis of normal vs. double-muscled cattle showing TGF-β domain-disrupting mutations

    PMID:9314496

    Open questions at the time
    • Did not define the receptor or downstream signaling cascade
    • Did not establish how the latent ligand is activated
  2. 2003 Medium

    Identifying IGFBP-3 as a mediator addressed how GDF8 suppresses myogenic proliferation beyond simple receptor engagement.

    Evidence Neutralizing antibody and mRNA/protein measurement in porcine embryonic myogenic cells

    PMID:14502562

    Open questions at the time
    • IGFBP-3 accounts for only part of the anti-proliferative effect
    • Single species/cell system
  3. 2005 High

    Demonstrating a Smad-independent p38/TAK1 arm answered whether GDF8 acts solely through canonical SMAD transcription, revealing a parallel anti-proliferative branch.

    Evidence Dominant-negative MKK6, SB203580 inhibition, ATF-2/Smad3/Smad4 Co-IP, and reporter/proliferation assays

    PMID:15567067

    Open questions at the time
    • Did not map how the receptor complex activates TAK1
    • Tissue-specific relevance not assessed
  4. 2007 Medium

    Extending myostatin action to bone showed it regulates mesenchymal lineage choice, broadening its role beyond myofibers.

    Evidence In vitro osteogenic differentiation of BMSCs with recombinant myostatin plus hindlimb unloading in KO mice

    PMID:17383950

    Open questions at the time
    • Receptor and SMAD dependence in BMSCs not dissected
    • Indirect (loading) and direct effects not fully separated
  5. 2008 Medium

    Loss-of-function and tissue-specific expression studies established that myostatin restrains fracture callus formation and acts in a cell-type-dependent manner.

    Evidence KO mouse fracture model with histomorphometry/biomechanics, and mammary gland expression profiling with proliferation/p21 assays

    PMID:18389502 PMID:18852073

    Open questions at the time
    • Cell-type-specific signaling differences (e.g. lack of p21 induction in mammary cells) unexplained
    • Direct progenitor targets not identified
  6. 2010 Medium

    Identifying pro-fibrogenic activity in ligament tissue established context-dependent stimulatory effects of myostatin, contrasting with its anti-proliferative muscle role.

    Evidence Recombinant myostatin treatment of primary ACL fibroblasts with collagen/tenascin/TGF-β1 readouts plus KO comparison

    PMID:20186835

    Open questions at the time
    • Downstream signaling branch driving fibrogenesis not defined
    • In vivo ligament relevance limited
  7. 2014 High

    Resolving the ActRIIA structure with a small-molecule inhibitor and rescuing myogenesis answered whether GDF8 receptor kinase signaling is pharmacologically druggable.

    Evidence Crystal structure of ActRIIA with dorsomorphin plus Smad2/3 and myoblast contractility/differentiation rescue assays

    PMID:25368322

    Open questions at the time
    • Inhibitors are not GDF8-selective
    • In vivo therapeutic window not established here
  8. 2017 High

    Structural comparison of GDF8 and GDF11 explained why two ligands sharing receptors differ in SMAD2/3 potency, localizing the difference to the type I receptor binding site.

    Evidence Crystal structures of GDF11:FS288, apo-GDF8 and apo-GDF11 plus chimeric mutagenesis and signaling assays

    PMID:28257634

    Open questions at the time
    • Physiological consequences of potency differences in vivo not resolved
    • Does not address ligand-specific antagonist selectivity
  9. 2017 Medium

    Gain- and loss-of-function in bone and oocytes refined the receptor logic, showing GDF8 inhibits bone formation/promotes resorption and activates p38 during oocyte maturation via ActRIIb-ALK4/5.

    Evidence Recombinant GDF8/neutralizing antibody in osteoblast and osteoclastogenesis assays in vivo, and p38/ROS/gene-expression readouts in porcine IVM

    PMID:28074479 PMID:28708509

    Open questions at the time
    • Direct versus indirect contributions to bone turnover not separated
    • Oocyte signaling mapped in a single species
  10. 2019 Medium

    Metabolic profiling of MSTN-null tissue and cardiac models established that myostatin loss reprograms AMPK-linked metabolism and limits pathological cardiac autophagy/hypertrophy.

    Evidence TMT proteomics/phosphoproteomics and AMPK assays in MSTN-/- cattle muscle; AAC/AngII hypertrophy models in MSTN-/- mice with AMPK/mTOR/PPARγ/NF-κB and miR-128 analysis

    PMID:31374285 PMID:31923740

    Open questions at the time
    • Whether metabolic and cardiac effects are cell-autonomous or secondary to muscle change unresolved
    • Direct ligand-to-AMPK link not established
  11. 2019 High

    Resolving the WFIKKN2 follistatin domain structure clarified how multiple antagonists converge on blocking type II receptor binding through distinct interfaces.

    Evidence 1.39 Å crystal structure, SPR binding, native gel shift, and alanine-scanning mutagenesis of WFIKKN2 FSD against GDF8/GDF11

    PMID:30814254

    Open questions at the time
    • In vivo antagonist hierarchy among follistatin/FSTL3/WFIKKN2 not ranked
    • Ligand-selective antagonism not engineered
  12. 2020 Medium

    Mechanistic dissection across reproductive and muscle tissues established ALK5-SMAD2/3 as the shared conduit for GDF8 effects on trophoblast invasion, granulosa metabolism, and epigenetic control of myogenesis.

    Evidence siRNA/pharmacological pathway blockade with invasion, glucose, and ChIP/methylation assays in EVT, hGL, and satellite cells

    PMID:32210722 PMID:33195207 PMID:33425488

    Open questions at the time
    • Each axis demonstrated in a single lab/cell system
    • How one ligand selects divergent transcriptional outputs per tissue is unexplained
  13. 2020 High

    Cross-species genetic editing and the GDF11-bone axis refined which residues control ligand activity and distinguished MSTN from GDF11 functionally in bone.

    Evidence CRISPR deletion of MSTN propeptide cysteine 42 in quail; Mstn-null, Gdf11-null and follistatin-overexpressing mice with histomorphometry and BMP signaling analysis

    PMID:32071240 PMID:32098368

    Open questions at the time
    • How propeptide cysteine 42 alters latency/activation mechanistically not defined
    • GDF11-mediated bone compensation in human contexts untested
  14. 2021 High

    Defining the prodomain residues required for tolloid cleavage answered how the latent complex is converted to active ligand and revealed a dominant-negative mode for resistant prodomains.

    Evidence Sequential alanine mutagenesis with Tll1 astacin-domain cleavage, acidic activation, and dominant-negative co-expression assays; plus ALK5-SMAD2/3-dependent MMP2/aromatase studies in EVT and granulosa cells

    PMID:33876824 PMID:34239360 PMID:34432647

    Open questions at the time
    • In vivo timing and location of tolloid activation not mapped
    • Whether dominant-negative prodomains are physiologically relevant unknown
  15. 2025 Medium

    Dual ligand blockade established GDF8 and activin A as the two principal ActRIIA/B ligands governing muscle mass and validated combined neutralization as a strategy to preserve muscle.

    Evidence Dual antibody blockade of GDF8 and activin A in obese mouse and non-human primate models with body composition analysis

    PMID:40360507

    Open questions at the time
    • Relative contribution of GDF8 versus activin A not separated
    • Long-term and human efficacy not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single ligand specifies divergent tissue-specific transcriptional outcomes through a common ALK5-SMAD2/3 axis, and how latent activation is spatially and temporally controlled in vivo, remain open.
  • No mechanism explaining tissue-specific co-factor selection
  • No in vivo map of where/when tolloid activates latent GDF8
  • Selectivity determinants distinguishing GDF8 from activin A and GDF11 signaling in vivo undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 2
Partners
ACVR1BACVR2BFSTFSTL3SMAD3TGFBR1TLL1WFIKKN2

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Loss-of-function mutations in myostatin (GDF8) cause the double-muscled phenotype in cattle: Belgian Blue cattle carry an 11-bp deletion causing a frameshift that removes the conserved TGF-β domain, and Piedmontese cattle carry a G-A transition changing a conserved cysteine to tyrosine, establishing myostatin as a negative regulator of muscle growth. cDNA cloning, sequence analysis of normal vs. double-muscled cattle, expression profiling Genome Research High 9314496
2005 GDF8 activates the p38 MAPK pathway through TGF-β-activated kinase 1 (TAK1), independently of Smad signaling. GDF8-induced transcriptional activation was inhibited by dominant-negative MKK6 or p38 inhibitor SB203580, and ATF-2 was phosphorylated and detected in a complex with Smad3/Smad4 upon GDF8 treatment. p38 MAPK was required for GDF8-induced inhibition of proliferation and upregulation of p21. Dominant-negative MKK6 expression, pharmacological p38 inhibition (SB203580), co-immunoprecipitation of ATF-2/Smad3/Smad4 complex, transcriptional reporter assays, proliferation assays Cellular Signalling High 15567067
2003 GDF8 (myostatin) suppresses proliferation of porcine embryonic myogenic cells partly through upregulation of IGFBP-3; an anti-IGFBP-3 neutralizing antibody reduced GDF8-mediated proliferation suppression, indicating IGFBP-3 mediates part of GDF8's anti-proliferative effect in myogenic cells. Cell proliferation assays, IGFBP-3 protein/mRNA measurement, anti-IGFBP-3 neutralizing antibody treatment Journal of Cellular Physiology Medium 14502562
2007 Loss of myostatin function increases osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro; the type IIB activin receptor (AcvrIIB) is expressed on BMSCs. Recombinant myostatin decreased expression of osteogenic factors BMP-2 and IGF-1 in BMSCs during mechanical loading, and the increased osteogenic differentiation was ablated by hindlimb unloading in vivo. In vitro osteogenic differentiation assay, immunofluorescence for AcvrIIB on BMSCs, recombinant myostatin treatment, hindlimb unloading model Bone Medium 17383950
2008 Myostatin deficiency increases fracture callus size, upregulates Sox-5 and BMP-2 expression in the fracture callus, and increases total osseous tissue area and callus strength, establishing myostatin as a regulator of fracture callus morphogenesis by inhibiting recruitment and proliferation of progenitor cells. Myostatin knockout mice, fibula osteotomy model, histomorphometry, three-point bending biomechanics, gene expression analysis Bone Medium 18852073
2010 Myostatin (GDF-8) and its receptor ActRIIB are expressed in human anterior cruciate ligament (ACL) tissue. Recombinant myostatin treatment of primary ACL fibroblasts increased cell proliferation and upregulated tenascin C, type 1 collagen, and TGF-β1 expression, identifying myostatin as a pro-fibrogenic factor in ligament tissue. Real-time PCR, immunohistochemistry, recombinant myostatin treatment of primary ACL fibroblasts, myostatin KO mouse comparison Journal of Orthopaedic Research Medium 20186835
2014 GDF8 signaling is inhibited by small molecule ATP-competitive inhibitors dorsomorphin and LDN-193189, which target GDF8-induced Smad2/3 signaling and repress myogenic transcription factors. Crystal structure of ActRIIA with dorsomorphin was resolved. Both inhibitors rescued myogenesis in GDF8-treated myoblasts and promoted contractile activity of myotubular networks. Crystal structure determination of ActRIIA with dorsomorphin, Smad2/3 phosphorylation assays, myoblast differentiation rescue assay, live cell contractility microscopy Journal of Biological Chemistry High 25368322
2017 GDF11 is a more potent activator of SMAD2/3 and signals more effectively through ALK4/5/7 than GDF8 despite high sequence similarity. Crystal structures of GDF11:FS288 complex, apo-GDF8, and apo-GDF11 revealed unique structural features in the type I receptor binding site of GDF11. Substitution of GDF11 residues into GDF8 conferred enhanced signaling activity to GDF8. SMAD2/3 signaling assays, crystal structure determination of GDF11:FS288, apo-GDF8, and apo-GDF11, chimeric protein mutagenesis BMC Biology High 28257634
2017 GDF8 inhibits bone formation and promotes bone resorption in mice. In vitro, GDF8 negatively regulated primary osteoblasts and promoted RANKL-induced osteoclastogenesis. In vivo, intraperitoneal injection of recombinant GDF8 repressed bone formation and accelerated bone resorption; a GDF8 neutralizing antibody stimulated new bone formation and prevented bone resorption in aged mice. Primary osteoblast culture with recombinant GDF8, osteoclastogenesis assay, in vivo intraperitoneal injection, neutralizing antibody treatment Clinical and Experimental Pharmacology and Physiology Medium 28074479
2019 WFIKKN2 follistatin domain (FSD) binds GDF8 and GDF11 and blocks their interaction with ActRIIB. Crystal structure of WFIKKN2 FSD was resolved to 1.39 Å; alanine substitution of surface-exposed residues reduced GDF8 antagonism. WFIKKN2 and follistatin both use their FSDs to block type II receptor binding but via different binding interactions. Native gel shift, surface plasmon resonance, crystal structure determination (1.39 Å), alanine scanning mutagenesis Journal of Biological Chemistry High 30814254
2021 Tolloid-mediated activation of latent GDF8 requires specific residues adjacent to the scissile bond (D99) in the prodomain, particularly Y94 and D92. Alanine mutations at these positions abolished tolloid-mediated activation of latent GDF8. Prodomain mutants (D92A, Y94A) resisted proteolysis but could be fully activated under acidic conditions. Co-expression of tolloid-resistant GDF8 prodomain mutants with WT GDF8 suppressed WT GDF8 activity in a dominant-negative manner. Sequential alanine mutagenesis, recombinant protein production and purification, protease cleavage assay with astacin domain of Tll1, acidic activation assay, dominant-negative co-expression assay Biochemical Journal High 33876824
2020 MSTN mutation (loss of function) promotes myogenic differentiation by increasing expression of demethylase TET1 via the SMAD2/SMAD3 pathway; ChIP-qPCR demonstrated that the SMAD2/SMAD3 complex binds the TET1 promoter to inhibit TET1 transcription. MSTN mutation reduces methylation of PAX3, PAX7, MyoD, and MyoG promoters. Overexpression of TET1 in WT cells promoted myogenic differentiation; knockdown of TET1 in MSTN mutant cells reversed the pro-myogenic effects. ChIP-qPCR, bisulfite sequencing/methylation analysis, TET1 overexpression and siRNA knockdown, myotube fusion index measurement, satellite cell differentiation assay International Journal of Biological Sciences Medium 32210722
2020 GDF8 (myostatin) upregulates SERPINE1 expression in granulosa-lutein cells via the ALK5-mediated SMAD2/3-SMAD4 signaling pathway, leading to glucose metabolism defects. ERK1/2 signaling was also activated by GDF8 but did not mediate SERPINE1 expression. TP53 was required for GDF8-stimulated SERPINE1 upregulation. siRNA-mediated knockdown, pharmacological inhibition (SB-431542), transcriptome sequencing, glucose metabolism assays in hGL cells Molecular Therapy: Nucleic Acids Medium 33425488
2020 GDF8 promotes cell invasiveness in human extravillous cytotrophoblast cells by upregulating FSTL3 expression via the ALK5-SMAD2/3 signaling pathway. siRNA-mediated knockdown of pathway components, recombinant GDF8 treatment, invasion assays in immortalized and primary EVT cells Frontiers in Cell and Developmental Biology Medium 33195207
2021 GDF-8 stimulates MMP2 expression (but not MMP9) in human EVT cells via the ALK5-SMAD2/3 signaling pathway, and GDF-8-induced cell invasiveness is dependent on MMP2 upregulation. siRNA-mediated knockdown of ALK5 and SMAD2/3, MMP2 knockdown, recombinant GDF-8 treatment, invasion assays Reproduction Medium 34432647
2021 GDF-8 stimulates aromatase (CYP19A1) expression and estradiol production in human granulosa-lutein cells via TGF-β type I receptor ALK5-mediated SMAD2/3 signaling. ALK5 inhibitor SB431542 reduced aromatase upregulation and alleviated OHSS symptoms in a rat model. Recombinant GDF-8 treatment, pharmacological ALK5 inhibition, rat OHSS model, human follicular fluid measurements, in vitro granulosa cell assays International Journal of Biological Sciences Medium 34239360
2019 MSTN deletion in cattle activates AMPK signaling pathways to regulate glucose and lipid metabolism, increasing activity of key enzymes in fatty acid β-oxidation and glycolysis, as shown by comparative proteomics and phosphoproteomics of MSTN-/- cattle muscle. Tandem mass tag (TMT) proteomic and phosphoproteomic analysis of MSTN-/- vs. WT cattle muscle, AMPK activity assays General and Comparative Endocrinology Medium 31374285
2019 MSTN deletion in mice attenuates cardiac hypertrophy by inhibiting excessive cardiac autophagy through inactivation of AMPK/mTOR signaling and activation of the PPARγ/NF-κB pathway. MSTN also downregulates miR-128, which targets PPARγ to aggravate cardiac hypertrophy. AAC and angiotensin II cardiac hypertrophy models in MSTN-/- mice and WT mice, Western blot for AMPK/mTOR/PPARγ/NF-κB, miR-128 expression analysis, in vitro cardiomyocyte assays Molecular Therapy: Nucleic Acids Medium 31923740
2017 GDF8 activates p38 MAPK signaling during porcine oocyte maturation in vitro through ActRIIb and Alk4/5 receptors, which upon GDF8 recognition induce phosphorylation of p38 MAPK and alter transcription of cumulus expansion genes (Has2, Ptx3, TNFAIP6) and Nrf2/Bcl-2, leading to reduced intracellular ROS and improved embryonic developmental competence. Recombinant GDF8 supplementation in IVM, p38 MAPK phosphorylation assay, gene expression analysis in oocytes and cumulus cells, ROS measurement, IVF/PA embryo developmental assay Theriogenology Medium 28708509
2020 Mstn deletion in mice enhances bone mass by upregulating GDF11 expression, which activates BMP signaling to enhance osteogenesis; Gdf11 null mice show reduced bone mass through impaired osteoblast and chondrocyte maturation and increased osteoclastogenesis. Mice overexpressing follistatin show increased muscle mass but bone fractures due to GDF11 inhibition, unlike Mstn null mice. Mstn null mice, Gdf11 null mice, follistatin overexpressing mice; histomorphometry, gene expression, BMP signaling pathway analysis PNAS High 32071240
2020 A single amino acid deletion (cysteine 42) in the MSTN propeptide region, caused by a 3-bp deletion, results in increased body weight and muscle mass via muscle hyperplasia in quail, demonstrating the functional importance of cysteine 42 in regulating MSTN activity in avian species. CRISPR/Cas9 adenoviral gene editing in quail, body weight and muscle mass measurement, histological analysis of muscle fiber number and size International Journal of Molecular Sciences Medium 32098368
2025 GDF8 (myostatin) and activin A are the two major ActRIIA/B ligands mediating muscle mass minimization. Dual blockade of GDF8 and activin A prevents GLP-1 receptor agonist-associated muscle loss and increases muscle mass in obese mice and non-human primates, with enhanced fat loss. Dual antibody blockade of GDF8 and activin A in obese mouse and NHP models, body composition analysis Nature Communications Medium 40360507
2008 GDF-8 expression in the mouse mammary gland is inversely correlated with differentiated state; highest GDF-8 mRNA levels occur during maximal ductal growth and diminish with pregnancy, reaching minimal levels at lactation. Unlike in muscle cells, GDF-8 did not reduce proliferation or induce p21 in mammary epithelial cells, revealing cell-type-specific activity. GDF-8 mRNA and protein expression profiling across mammary gland development stages, Smad2/3 phosphorylation assay, mammary epithelial cell proliferation assay, p21 induction assay Molecular Reproduction and Development Medium 18389502

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Mutations in myostatin (GDF8) in double-muscled Belgian Blue and Piedmontese cattle. Genome research 846 9314496
2010 Myostatin (GDF-8) as a key factor linking muscle mass and bone structure. Journal of musculoskeletal & neuronal interactions 166 20190380
2007 Loss of myostatin (GDF8) function increases osteogenic differentiation of bone marrow-derived mesenchymal stem cells but the osteogenic effect is ablated with unloading. Bone 145 17383950
2010 A sequence polymorphism in MSTN predicts sprinting ability and racing stamina in thoroughbred horses. PloS one 144 20098749
2015 Generation of gene-modified goats targeting MSTN and FGF5 via zygote injection of CRISPR/Cas9 system. Scientific reports 134 26354037
2005 Regulation of GDF-8 signaling by the p38 MAPK. Cellular signalling 115 15567067
2006 GRB14, GPD1, and GDF8 as potential network collaborators in weight loss-induced improvements in insulin action in human skeletal muscle. Physiological genomics 112 16849634
2017 Structural basis for potency differences between GDF8 and GDF11. BMC biology 97 28257634
1999 Frequent sequence variation in the human myostatin (GDF8) gene as a marker for analysis of muscle-related phenotypes. Genomics 90 10610713
2009 Polymorphisms in the ovine myostatin gene (MSTN) and their association with growth and carcass traits in New Zealand Romney sheep. Animal genetics 82 19799595
2009 A frameshift mutation in the coding region of the myostatin gene (MSTN) affects carcass conformation and fatness in Norwegian White Sheep (Ovis aries). Animal genetics 75 19392824
2008 Myostatin (GDF-8) deficiency increases fracture callus size, Sox-5 expression, and callus bone volume. Bone 70 18852073
2007 Evidence for multiple alleles effecting muscling and fatness at the ovine GDF8 locus. BMC genetics 64 17996073
2020 GDF11 promotes osteogenesis as opposed to MSTN, and follistatin, a MSTN/GDF11 inhibitor, increases muscle mass but weakens bone. Proceedings of the National Academy of Sciences of the United States of America 61 32071240
2008 Two single nucleotide polymorphisms in the myostatin (GDF8) gene have significant association with muscle depth of commercial Charollais sheep. Animal genetics 58 18462481
2014 Efficient generation of myostatin (MSTN) biallelic mutations in cattle using zinc finger nucleases. PloS one 57 24743319
2016 Isozygous and selectable marker-free MSTN knockout cloned pigs generated by the combined use of CRISPR/Cas9 and Cre/LoxP. Scientific reports 56 27530319
2007 Myostatin (MSTN) gene duplications in Atlantic salmon (Salmo salar): evidence for different selective pressure on teleost MSTN-1 and -2. Gene 52 17890020
2018 CRISPR/Cas9-mediated MSTN disruption and heritable mutagenesis in goats causes increased body mass. Animal genetics 48 29446146
2014 Small molecules dorsomorphin and LDN-193189 inhibit myostatin/GDF8 signaling and promote functional myoblast differentiation. The Journal of biological chemistry 48 25368322
2020 Muscle Hyperplasia in Japanese Quail by Single Amino Acid Deletion in MSTN Propeptide. International journal of molecular sciences 46 32098368
2019 MSTN Attenuates Cardiac Hypertrophy through Inhibition of Excessive Cardiac Autophagy by Blocking AMPK /mTOR and miR-128/PPARγ/NF-κB. Molecular therapy. Nucleic acids 46 31923740
2017 Inhibition of GDF8 (Myostatin) accelerates bone regeneration in diabetes mellitus type 2. Scientific reports 42 28852138
2021 Production of MSTN-mutated cattle without exogenous gene integration using CRISPR-Cas9. Biotechnology journal 39 34247443
2025 GDF8 and activin A blockade protects against GLP-1-induced muscle loss while enhancing fat loss in obese male mice and non-human primates. Nature communications 37 40360507
2020 MSTN Mutant Promotes Myogenic Differentiation by Increasing Demethylase TET1 Expression via the SMAD2/SMAD3 Pathway. International journal of biological sciences 36 32210722
2009 Investigations into the GDF8 g+6723G-A polymorphism in New Zealand Texel sheep. Journal of animal science 35 19251921
2011 Whole body cortisol and expression of HSP70, IGF-I and MSTN in early development of sea bass subjected to heat shock. General and comparative endocrinology 34 21872596
2005 A directed search in the region of GDF8 for quantitative trait loci affecting carcass traits in Texel sheep. Journal of animal science 33 16100053
2021 Long-term, multidomain analyses to identify the breed and allelic effects in MSTN-edited pigs to overcome lameness and sustainably improve nutritional meat production. Science China. Life sciences 32 34109474
2014 The A55T and K153R polymorphisms of MSTN gene are associated with the strength training-induced muscle hypertrophy among Han Chinese men. Journal of sports sciences 32 24479661
2011 Polymorphisms of myostatin gene (MSTN) in four goat breeds and their effects on Boer goat growth performance. Molecular biology reports 32 21710248
2020 CRISPR/Cas9-mediated MSTN disruption accelerates the growth of Chinese Bama pigs. Reproduction in domestic animals = Zuchthygiene 31 32679613
2020 Aberrant elevation of GDF8 impairs granulosa cell glucose metabolism via upregulating SERPINE1 expression in patients with PCOS. Molecular therapy. Nucleic acids 31 33425488
2003 Mapping modifiers affecting muscularity of the myostatin mutant (Mstn(Cmpt-dl1Abc)) compact mouse. Genetics 31 14504233
2019 IMB0901 inhibits muscle atrophy induced by cancer cachexia through MSTN signaling pathway. Skeletal muscle 30 30922397
2019 Comparison of gene editing efficiencies of CRISPR/Cas9 and TALEN for generation of MSTN knock-out cashmere goats. Theriogenology 30 30981084
2018 CRISPR/Cas9-mediated sheep MSTN gene knockout and promote sSMSCs differentiation. Journal of cellular biochemistry 30 30242885
2018 Genotypic and allelic effects of the myostatin gene (MSTN) on carcass, meat quality, and biometric traits in Colored Polish Merino sheep. Meat science 30 30658164
2017 GDF8 inhibits bone formation and promotes bone resorption in mice. Clinical and experimental pharmacology & physiology 30 28074479
2016 Establishment and phenotypic analysis of an Mstn knockout rat. Biochemical and biophysical research communications 30 27289021
2014 Effective RNA-silencing strategy of Lv-MSTN/GDF11 gene and its effects on the growth in shrimp, Litopenaeus vannamei. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 30 25246367
2009 Myostatin (GDF8) single nucleotide polymorphisms in Nellore cattle. Genetics and molecular research : GMR 30 19731204
2019 Proteomics insights into the effects of MSTN on muscle glucose and lipid metabolism in genetically edited cattle. General and comparative endocrinology 27 31374285
2012 Molecular characterization of myostatin (MSTN) gene and association analysis with growth traits in the bighead carp (Aristichthys nobilis). Molecular biology reports 27 22714921
2011 Analysis of the single-nucleotide polymorphism in the 5'UTR and part of intron I of the sheep MSTN gene. DNA and cell biology 27 21323579
2003 Role of insulin-like growth factor binding protein (IGFBP)-3 in TGF-beta- and GDF-8 (myostatin)-induced suppression of proliferation in porcine embryonic myogenic cell cultures. Journal of cellular physiology 27 14502562
2020 Effective MSTN Gene Knockout by AdV-Delivered CRISPR/Cas9 in Postnatal Chick Leg Muscle. International journal of molecular sciences 25 32276422
2018 CRISPR/Cas9-mediated specific integration of fat-1 at the goat MSTN locus. The FEBS journal 25 29802684
2007 Characterization of amphioxus GDF8/11 gene, an archetype of vertebrate MSTN and GDF11. Development genes and evolution 25 17551751
2022 Optimized Cas9:sgRNA delivery efficiently generates biallelic MSTN knockout sheep without affecting meat quality. BMC genomics 24 35524183
2020 Effect of MSTN Mutation on Growth and Carcass Performance in Duroc x Meishan Hybrid Population. Animals : an open access journal from MDPI 24 32481564
2019 Prevalence of DLL3, CTLA-4 and MSTN Expression in Patients with Small Cell Lung Cancer. OncoTargets and therapy 24 31819500
2010 Role of myostatin (GDF-8) signaling in the human anterior cruciate ligament. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 24 20186835
2020 Effects of electroporation treatment using different concentrations of Cas9 protein with gRNA targeting Myostatin (MSTN) genes on the development and gene editing of porcine zygotes. Animal science journal = Nihon chikusan Gakkaiho 23 32512638
2020 Myostatin (MSTN) Gene Indel Variation and Its Associations with Body Traits in Shaanbei White Cashmere Goat. Animals : an open access journal from MDPI 22 31963797
2019 Comparative analysis of silencing expression of myostatin (MSTN) and its two receptors (ACVR2A and ACVR2B) genes affecting growth traits in knock down chicken. Scientific reports 22 31127166
2017 GDF8 activates p38 MAPK signaling during porcine oocyte maturation in vitro. Theriogenology 21 28708509
2014 Identification and expression characterization of the myostatin (MSTN) gene and association analysis with growth traits in the razor clam Sinonovacula constricta. Gene 21 25447910
2010 Age-related changes in craniofacial morphology in GDF-8 (myostatin)-deficient mice. Anatomical record (Hoboken, N.J. : 2007) 21 19899116
2009 An insertion in the coding region of the myostatin (MSTN) gene affects carcass conformation and fatness in the Norwegian Spaelsau (Ovis aries). BMC research notes 21 19505313
2020 Exogenous GDF11, but not GDF8, reduces body weight and improves glucose homeostasis in mice. Scientific reports 20 32165710
2020 GDF8 Promotes the Cell Invasiveness in Human Trophoblasts by Upregulating the Expression of Follistatin-Like 3 Through the ALK5-SMAD2/3 Signaling Pathway. Frontiers in cell and developmental biology 20 33195207
2019 The contribution of myostatin (MSTN) and additional modifying genetic loci to race distance aptitude in Thoroughbred horses racing in different geographic regions. Equine veterinary journal 20 30604488
2019 Growth Differentiation Factor-8 (GDF8)/Myostatin is a Predictor of Troponin I Peak and a Marker of Clinical Severity after Acute Myocardial Infarction. Journal of clinical medicine 20 31906236
2013 Targeted disruption of the sheep MSTN gene by engineered zinc-finger nucleases. Molecular biology reports 20 24197697
2022 Germline transmission of MSTN knockout cattle via CRISPR-Cas9. Theriogenology 19 36037573
2019 Inhibition of MSTN signal pathway may participate in LIPUS preventing bone loss in ovariectomized rats. Journal of bone and mineral metabolism 19 31414284
2020 Mutation in myostatin 3'UTR promotes C2C12 myoblast proliferation and differentiation by blocking the translation of MSTN. International journal of biological macromolecules 18 32156541
2020 MSTN is a key mediator for low-intensity pulsed ultrasound preventing bone loss in hindlimb-suspended rats. Bone 18 32829040
2013 Polymorphisms of the myostatin gene (MSTN) and its relationship with growth traits in goat breeds. Genetics and molecular research : GMR 18 23613242
2024 A MSTNDel73C mutation with FGF5 knockout sheep by CRISPR/Cas9 promotes skeletal muscle myofiber hyperplasia. eLife 17 39365728
2019 Expression of MSTN gene and its correlation with pectoralis muscle fiber traits in the domestic pigeons (Columba livia). Poultry science 17 31265735
2017 Interaction with the GDF8/11 pathway reveals treatment options for adenocarcinoma of the breast. Breast (Edinburgh, Scotland) 17 29156385
2008 Mammary gland differentiation inversely correlates with GDF-8 expression. Molecular reproduction and development 17 18389502
2021 GDF-8 stimulates trophoblast cell invasion by inducing ALK5-SMAD2/3-mediated MMP2 expression. Reproduction (Cambridge, England) 16 34432647
2019 Crystal structure of the WFIKKN2 follistatin domain reveals insight into how it inhibits growth differentiation factor 8 (GDF8) and GDF11. The Journal of biological chemistry 16 30814254
2014 MSTN, mTOR and FoxO4 are involved in the enhancement of breast muscle growth by methionine in broilers with lower hatching weight. PloS one 16 25437444
2013 Genetic variations in the myostatin gene (MSTN) in New Zealand sheep breeds. Molecular biology reports 16 24081623
2016 Quantitative measurements of GDF-8 using immunoaffinity LC-MS/MS. Proteomics. Clinical applications 15 26846723
2012 Assessment of tools for marker-assisted selection in a marine commercial species: significant association between MSTN-1 gene polymorphism and growth traits. TheScientificWorldJournal 15 22666112
2009 Characterization of myostatin/gdf8/11 in the starlet sea anemone Nematostella vectensis. Journal of experimental zoology. Part B, Molecular and developmental evolution 15 19533681
2023 Resistance exercise alleviates dexamethasone-induced muscle atrophy via Sestrin2/MSTN pathway in C57BL/6J mice. Experimental cell research 14 37709247
2019 GDF8 enhances SOX2 expression and blastocyst total cell number in porcine IVF embryo development. Theriogenology 14 30825707
2018 Effects of fasting and re-feeding on mstn and mstnb genes expressions in Cranoglanis bouderius. Gene 14 30267811
2022 MSTN Regulatory Network in Mongolian Horse Muscle Satellite Cells Revealed with miRNA Interference Technologies. Genes 13 36292721
2019 Label-Free LC-MS/MS Proteomics Analyses Reveal Proteomic Changes Accompanying MSTN KO in C2C12 Cells. BioMed research international 13 31073529
2022 Association of Myostatin Gene Polymorphisms with Strength and Muscle Mass in Athletes: A Systematic Review and Meta-Analysis of the MSTN rs1805086 Mutation. Genes 12 36360291
2021 A highly prevalent SINE mutation in the myostatin (MSTN) gene promoter is associated with low circulating myostatin concentration in Thoroughbred racehorses. Scientific reports 12 33846367
2021 High ovarian GDF-8 levels contribute to elevated estradiol production in ovarian hyperstimulation syndrome by stimulating aromatase expression. International journal of biological sciences 12 34239360
2021 MSTN is an important myokine for weight-bearing training to attenuate bone loss in ovariectomized rats. Journal of physiology and biochemistry 12 34453705
2019 Significant body mass increase by oral administration of a cascade of shIL21-MSTN yeast-based DNA vaccine in mice. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 12 31302418
2013 Characterization of myostatin gene (MSTN) of Pekin duck and the association of its polymorphism with breast muscle traits. Genetics and molecular research : GMR 12 23479163
2006 SNP identification and analysis in part of intron 2 of goat MSTN gene and variation within and among species. The Journal of heredity 12 16624893
2021 Characterization of tolloid-mediated cleavage of the GDF8 procomplex. The Biochemical journal 11 33876824
2022 Differential Expression of MSTN Isoforms in Muscle between Broiler and Layer Chickens. Animals : an open access journal from MDPI 10 35268106
2020 Functional identification and characterization of IpMSTNa, a novel orthologous myostatin (MSTN) gene in channel catfish Ictalurus punctatus. International journal of biological macromolecules 10 32045608
2014 Identification of two SNPs in myostatin (MSTN) gene of Takifugu rubripes and their association with growth traits. Molecular and cellular probes 10 24721142
2023 Production of MSTN Gene-Edited Embryos of Buffalo Using the CRISPR/Cas9 System and SCNT. Cellular reprogramming 9 37042654
2022 Esophageal striated muscle hypertrophy and muscle fiber type transformation in MSTN knockout pigs. Transgenic research 9 35570234

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