MGF (Mechano Growth Factor)

What it is

Mechano Growth Factor (MGF) is a splice isoform of the insulin-like growth factor 1 (IGF-1) gene, produced by alternative splicing in response to mechanical stimulation, injury, or exercise in skeletal muscle and other tissues (PMID 28553731; PMID 14609023; PMID 12023866). Due to a reading frame shift arising from a 49-base-pair insert (in humans) in exon 5 of the IGF-1 gene, MGF has a unique C-terminal (E domain) peptide sequence distinct from systemic IGF-1Ea (PMID 16463438; PMID 11915923). The E domain peptide is responsible for activating mononucleated satellite (stem) cells in skeletal muscle to support local repair and hypertrophy (PMID 31271846; PMID 14609023). Full-length MGF can also directly activate the IGF-I receptor (IGF-IR), the insulin receptor-A (IR-A), and the insulin receptor-B (IR-B), though with higher EC50 values than recombinant IGF-1. In skeletal muscle, MGF is anti-apoptotic, promotes satellite cell proliferation, and inhibits terminal differentiation of myoblasts; its production declines with age and in certain muscular dystrophies (PMID 16463438; PMID 15501012; PMID 28553731). MGF E peptide has also been shown to exert effects in anterior cruciate ligament fibroblasts via MEK-ERK1/2 and PI3K-Akt signaling pathways (PMID 28553731; PMID 30317597), in chondrocytes via regulation of cell proliferation, migration, differentiation, and apoptosis, in cardiac myocytes as an anti-apoptotic and stem cell homing factor, and in periodontal ligament cells via Fyn-FAK kinase and MAPK signaling. MGF is not glycosylated, is smaller, and has a shorter half-life in the unbound state compared to systemic liver-type IGF-1.

Class: IGF-1 splice variant / peptide growth factor

What it's studied for

• Skeletal muscle maintenance, repair, and hypertrophy (including sarcopenia and muscle wasting) Animal studies only
  • MGF is produced as a pulse following mechanical challenge and activates satellite (stem) cells for muscle repair and hypertrophy. MGF deficiency is associated with muscular dystrophies and sarcopenia. Delivery of MGF cDNA or peptide produces marked increases in strength of normal and diseased muscle. PMID 16463438 Goldspink G. Impairment of IGF-I gene splicing and MGF expression associated with muscle wasting. Int J Biochem Cell Biol. 2006.
  • The ability to produce MGF declines with age and is linked to declining growth hormone levels. GH treatment upregulates IGF-I gene expression and, combined with resistance exercise, increases splicing towards MGF, potentially ameliorating sarcopenia. PMID 15501012 Goldspink G, Harridge SDR. Growth factors and muscle ageing. Exp Gerontol. 2004.
  • MGF-24aa-E peptide significantly increased the proliferative life span and delayed senescence of satellite cells from neonatal and young adult (but not old adult) human muscle in culture. Hypertrophy was observed in all cultures. MGF-E alone enhanced satellite cell activation, proliferation, and fusion. PMID 21354439 Kandalla PK et al. Mechano Growth Factor E peptide (MGF-E) activates human muscle progenitor cells and induces an increase in their fusion potential at different ages. Mech Ageing Dev. 2011.
  • MGF C-terminal peptide acts as a separate growth factor, initially activating mononucleated myoblasts (satellite cells). MGF over-expression results in hypertrophy in normal muscle. PMID 14609023 Goldspink G. Gene expression in muscle in response to exercise. J Muscle Res Cell Motil. 2003.
• Bone defect healing and osteogenesis Animal studies only
  • T-MGF-19E peptide promoted MC3T3-E1 osteoblast proliferation, differentiation, and mineralization in vitro. In a rabbit bone defect model, low-dose T-MGF-19E peptide significantly promoted bone injury healing. PMID 32339623 Wei W et al. MGF-19E peptide promoted proliferation, differentiation and mineralization of MC3T3-E1 cell and promoted bone defect healing. Gene. 2020.
• Cartilage repair and osteoarthritis Animal studies only
  • MGF combined with TGF-β3 in silk fibroin scaffolds increased cell recruitment up to 1.8–2 times vs TGF-β3 alone, enhanced collagen II and aggrecan secretion, and produced the best integration and cartilage-like architecture in a rabbit osteochondral defect model. PMID 25818452 Luo Z et al. Mechano growth factor (MGF) and transforming growth factor (TGF)-β3 functionalized silk scaffolds enhance articular hyaline cartilage regeneration in rabbit model. Biomaterials. 2015.
  • MGF is highly expressed in chondrocytes, especially in damaged cartilage. It plays roles in chondrocyte proliferation, migration, differentiation, inflammatory reactions, and apoptosis. Its role in cartilage development and disease is reviewed as still controversial. PMID 37171185 Liu Y et al. The role of mechano growth factor in chondrocytes and cartilage defects: a concise review. Acta Biochim Biophys Sin. 2023.
• Anterior cruciate ligament (ACL) repair Mixed
  • MGF E peptide pretreatment decreased type I/III collagen synthesis acutely but improved type III collagen synthesis at 24 h post-injury, decreased MMP-2 activity, and accelerated cell proliferation via MEK-ERK1/2 in human ACL fibroblasts. PMID 28553731 Sha Y et al. MGF E peptide pretreatment improves collagen synthesis and cell proliferation of injured human ACL fibroblasts via MEK-ERK1/2 signaling pathway. Growth Factors. 2017.
  • MGF E peptide protected ACL fibroblasts against hypoxia-induced apoptosis via mitochondrial, MEK-ERK1/2, and PI3K-Akt pathways. In a rabbit ACL rupture model, MGF E peptide decreased apoptosis, facilitated cell proliferation, and accelerated angiogenesis via SDF-1α/CXCR4 and VEGF. PMID 30317597 Sha Y et al. MGF E peptide improves anterior cruciate ligament repair by inhibiting hypoxia-induced cell apoptosis and accelerating angiogenesis. J Cell Physiol. 2019.
• Cardiac protection and myocyte survival (stem cell recruitment) Animal studies only
  • MGF peptide-loaded PEGDMA microrods delivered MGF for 2 weeks. MGF microrod treatment increased hMSC migration (1.72-fold) and protected neonatal rat ventricular myocytes from hypoxia-induced apoptosis, shown by TUNEL assay and increased Bcl-2 expression. PMID 24908137 Doroudian G et al. Sustained delivery of MGF peptide from microrods attracts stem cells and reduces apoptosis of myocytes. Biomed Microdevices. 2014.
• Periodontal ligament regeneration Animal studies only
  • MGF produced from periodontal ligament (PDL) under occlusion force enhanced PDL remodeling in vivo. In vitro, MGF enhanced PDL stem cell differentiation toward fibroblasts via Fyn-FAK and MAPK (ERK1/2, p38) pathways. Enhanced PDL regeneration under combined MGF and occlusal force was confirmed in vivo. PMID 38193124 Zhao Y et al. Mechanochemical coupling of MGF mediates periodontal regeneration. Bioeng Transl Med. 2024.
• Neural stem cell proliferation and neuroprotection (ischemia/hypoxia context) Animal studies only
  • Exogenous MGF application increased neural stem cell (NSC) proliferation and migration rate in all oxygen conditions (0%, 3%, 20% O2). MGF upregulated HIF-1α gene expression in anoxic conditions. Results suggest neuroprotective and proliferative roles for exogenous MGF in ischemia. PMID 39403354 Aydıntuğ-Gürbüz T et al. The Effects of IGF1 and MGF on Neural Stem Cells in Hypoxic Conditions. Basic Clin Neurosci. 2024.
• Muscle adaptation after orthognathic surgery Human observational
  • In 29 adult patients, MGF mRNA in masseter muscle was significantly upregulated (P<.005) 6 months after orthognathic surgery. Coherence of increased MGF expression and MyHC isoform shift indicated adequate muscle adaptation and higher mastication activity. PMID 18568377 Maricic N et al. MGF- and myostatin-mRNA regulation in masseter muscle after orthognathic surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008.
• Immune modulation during overload exercise training Animal studies only
  • In rats, 11 weeks of overload training significantly increased MGF mRNA in macrophages (92-fold, P<0.01). In vitro, MGF peptide (1–100 ng/mL) impaired macrophage phagocytosis and inhibited ROS generation in a dose-independent manner, suggesting MGF mediates training-induced immune suppression. PMID 22592456 Xiao W et al. Overload training inhibits phagocytosis and ROS generation of peritoneal macrophages: role of IGF-1 and MGF. Eur J Appl Physiol. 2013.
• Doping / performance enhancement (misuse context — anti-doping detection) In vitro only
  • A full-length MGF derivative (monoisotopic mass 12264.9 Da, closely related to IGF-1Ec, with R109H substitution and terminal lysine elimination) was identified in illicit products. It was detectable at 0.25 ng/mL by immunoaffinity purification followed by nanoscale LC-HRMS. WADA has prohibited MGF since 2005. PMID 25466910 Thevis M et al. Mass spectrometric characterization of a biotechnologically produced full-length mechano growth factor (MGF) relevant for doping controls. Growth Horm IGF Res. 2014.
  • MGF R23H (a variant of MGF) was identified in confiscated vials. In vitro plasma metabolism experiments showed MGF R23H has good stability and should be detectable in urine. PMID 17 Cox HD et al. Detection and in vitro metabolism of the confiscated peptides BPC 157 and MGF R23H. Drug Test Anal. 2017.
  • At high equimolar concentrations, full-length MGF activated the IGF-IR to a similar maximal extent as recombinant IGF-1 (89-fold vs 77-fold). EC50 for full-length MGF at IGF-IR was 7.83 nmol/L vs 0.86 nmol/L for IGF-1. Human MGF and Goldspink-MGF (24aa E peptide forms) showed no IGF-IR activation. PMID 26991004 Janssen JAMJL et al. Potency of Full-Length MGF to Induce Maximal Activation of the IGF-I R Is Similar to Recombinant Human IGF-I at High Equimolar Concentrations. PLoS One. 2016.

Community-reported dosing

Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.

Safety signals

• MGF peptide impaired macrophage phagocytosis (dose-independent) and inhibited ROS generation at 1, 10, 50, and 100 ng/mL in vitro, suggesting potential immune suppression at these concentrations PMID 22592456
• Full-length MGF activates the IGF-I receptor, insulin receptor-A, and insulin receptor-B in vitro at high concentrations, raising theoretical concerns about off-target metabolic effects (e.g., insulin-like hypoglycemia); human in vivo safety data are absent PMID 26991004
• Illicit full-length MGF products identified in confiscated vials contained a derivative with R109H substitution and terminal lysine elimination — composition may differ from what is advertised, raising purity and identity concerns PMID 25466910
• MGF R23H (a stabilized MGF variant found in confiscated vials) showed good plasma stability in vitro, suggesting prolonged systemic exposure if administered; no human safety or elimination kinetics data are available PMID 17

Contraindications

• No formal contraindications for human use are stated in the reviewed literature. The reviewed abstracts do not describe any human clinical trials of exogenous MGF administration. PMID 26991004