Mechano Growth Factor (MGF) Peptide Actions on Muscular Tissue, Bone and Cartilage Cells

Mechano Growth Factor is a 24‐amino acid peptide derived from an alternatively spliced isoform of IGF‐1 (an anabolic mediator of growth hormone), specifically the IGF-IEc variant.⁽¹⁾ Scientists propose proteolytic processing of this isoform to yield both the mature 70–amino acid IGF-I and the separate Mechano Growth Factor peptide. Consequently, Mechano Growth Factor is also sometimes termed as MGF-Ct24E, MGF-24aa-E, or “E-domain of IGF-1Ec”. Yet, endogenous MGF has not been isolated from tissue, and the current research comes from studies using synthetic analogs of the peptide.⁽²⁾

Expression of the IGF-IEc isoform and splicing to Mechano Growth Factor is believed to be induced when muscle cells are exposed to mechanical stress. This may occur in laboratory settings during simulated exercise. However, the exact regulatory mechanisms behind this induction remain unclear. Synthetic Mechano Growth Factor is often exposed to research models to simulate these processes in laboratory settings and investigate their potential roles in various cellular processes. Researchers are examining its potential for muscle cell repair and regeneration, particularly its ability to activate satellite cells, promote muscle cell hypertrophy, and even impact cardiac cell function.

 

Research

Mechano Growth Factor and Muscle Cell Hypertrophy

Research by Li et al. posits that Mechano Growth Factor may stimulate muscle cell hypertrophy through a signaling cascade that involves ERK5 and MEF2C.⁽¹⁾ ERK5, a member of the mitogen-activated protein kinase family, is believed to be activated by Mechano Growth Factor via a yet-to-be-defined receptor, resulting in its phosphorylation and subsequent translocation into the nucleus.

Once in the nucleus, ERK5 may facilitate the activation of MEF2C, a muscular tissue-specific transcription factor that is suggested to regulate genes involved in muscular tissue growth and differentiation. Li et al. suggest that the activation of MEF2C is critical, as it may upregulate the expression of muscular tissue-specific proteins that contribute to hypertrophy. This proposed pathway is said to offer a potential mechanism of muscle cell growth that appears to operate independently of the classical IGF-I receptor-mediated signals. However, further investigation is needed to fully elucidate the precise molecular interactions in murine models.

Furthermore, Kandalla et al. suggest that Mechano Growth Factor may also, in some way, promote muscle cell hypertrophy by interacting with satellite cells.⁽³⁾ These muscle cell cultures displayed an increased fusion index, and the mean number of nuclei per myotube was markedly elevated—by approximately 150 to 220%, depending on the timing of these relevant implications. This may indicate that the hypertrophic action might occur independently of additional cell proliferation. Moreover, researchers studying peptide-exposed cell cultures observed an increased expression of contractile proteins, as measured by the ratio of myosin heavy chain to a nuclear marker.

This finding implies that the peptide may support contractile protein synthesis. Additionally, the observed reduction in the proportion of unfused reserve cells further supports the idea that the peptide may recruit these cells into the differentiating myotubes, thereby contributing to the hypertrophic phenotype. Consequently, research by Janssen et al. has suggested that Mechano Growth Factor (before its splicing from IGF-IEc) may have “resulted in a 25% increase in the mean muscle fiber cross-sectional area” in laboratory settings.⁽⁴⁾ Yet, similar research with the spliced Mechano Growth Factor variant remains to be conducted.

Mechano Growth Factor and Oxidative Stress

Findings from research by Liu X. et al. suggest that Mechano Growth Factor may modulate oxidative stress in injured skeletal muscle cells under conditions of macrophage depletion.⁽⁵⁾ More specifically, Mechano Growth Factor appeared to lower the oxidative stress environment, as indicated by decreased expression of gp91phox—a key subunit of NADPH oxidases that is posited to be involved in reactive oxygen species generation. The study measured gp91phox levels with both RT-PCR and immunofluorescence staining at 3 and 14 days post-injury, and the results suggest that Mechano Growth Factor may potentially reduce gp91phox expression compared with controls.

This reduction may be indicative of lower activity of NADPH oxidases. This may contribute to the potential diminishing of the generation of reactive oxygen species that are implicated in fibrotic scar formation. Although the exact mechanism remains to be fully elucidated, these findings possibly imply that Mechano Growth Factor might modulate oxidative stress in the injured skeletal muscle cells, which might prove to be relevant for tissue remodeling. The data, therefore, support the hypothesis that Mechano Growth Factor might have potential antioxidant properties under conditions where macrophage activity is depleted. However, further studies would be necessary to confirm the underlying pathways involved.

Mechano Growth Factor and Cardiac Cells

A study by Doroudian et al. also suggests that Mechano Growth Factor may exhibit potential anti-apoptotic actions on heart muscle cells under stress simulation in laboratory conditions.⁽⁶⁾ More specifically, the peptide is posited to confer cellular protection by modulating intrinsic cell survival pathways. For example, the researchers performed a TUNEL assay—a method that labels free 3’-OH termini generated during DNA fragmentation— which served as an indicator of apoptotic activity.

An observed reduction in TUNEL-positive signals during Mechano Growth Factor evaluation suggested that fewer cardiac muscle cells were undergoing programmed cell death. In parallel, increased expression of Bcl-2, a protein thought to inhibit apoptosis by maintaining mitochondrial membrane integrity and mitigating the release of pro-apoptotic factors like cytochrome c, indicated that the cellular environment was potentially more resistant to stress-induced apoptosis following the introduction of Mechano Growth Factor. Collectively, these observations suggest that Mechano Growth Factor may help mitigate cell death in cardiomyocytes under hypoxic laboratory conditions, possibly by attenuating apoptotic signaling pathways and supporting cell survival.

Mechano Growth Factor and Cartilage Cells

Preliminary research by a group of scientists led by Liu Y. et al. has reviewed the available scientific data on the potential actions of Mechano Growth Factor cartilage cells.⁽⁷⁾ Based on the collected data, the researchers posit that Mechano Growth Factor may impact several cellular behaviors. For instance, it appears that Mechano Growth Factor may support cell migration, potentially by promoting cytoskeletal reorganization and focal adhesion formation through pathways such as RhoA/YAP. This reorganization may facilitate the extension of cell processes, which may be important for cartilage tissue repair. Additionally, Mechano Growth Factor may impact the synthesis and composition of the extracellular matrix.

Data suggests that in injured cartilage, Mechano Growth Factor might promote the production of key components like type II collagen and aggrecan while downregulating fibrotic markers such as type I collagen. This balance might prove to be crucial for maintaining cartilage homeostasis and ensuring that repair processes lead to the regeneration of tissue resembling endogenous cartilage rather than scar tissue. Moreover, under conditions of mechanical overload or hypoxia, Mechano Growth Factor appears to have protective potential on chondrocytes.

It is posited that Mechano Growth Factor may reduce the activation of apoptotic pathways by modulating the expression of proteins in the Bcl-2 family and by inhibiting caspase activation. At the same time, Mechano Growth Factor might also attenuate inflammatory responses by downregulating pro-inflammatory cytokines such as IL-1β and TNF-α, which are believed to exacerbate cartilage degradation.

Mechano Growth Factor and Bone Cells

In vitro experiments by Deng et al. that involve the Mechano Growth Factor peptide and MC3T3-E1 osteoblast-like cells suggested that the peptide may promote cell proliferation. This may be even more the case than with either IGF-IEc or IGF-1 due to a pro-proliferative activity that “was 1.4 times greater than that of IGF-1.”⁽⁸⁾ This better-supported proliferation appears to be mediated through two interrelated mechanisms. First, Mechano Growth Factor may support changes in cell cycle distribution by supporting arrest in the S and G2/M phases. This may increase DNA synthesis and mitotic activity. Second, the peptide may predominantly activate the MAPK-Erk1/2 signaling pathway, as supported by data displaying increased phosphorylation of Erk1/2 while exhibiting minimal impact on Akt phosphorylation.

The exposure of research models to pathway-specific inhibitors further supports this notion. It has been observed that inhibition of Erk1/2 markedly mitigates peptide-related proliferation, whereas inhibition of the PI3K/Akt pathway appeared to have little impact. Furthermore, Deng et al. conducted additional studies in which Mechano Growth Factor also appeared to support bone tissue recovery in research models. Radiographic evaluations support the idea that bone defects exposed to Mechano Growth Factor presented features such as cortical bridging and disappearance of the fracture line and ultimately suggested an accelerated remodeling process.

Histological assessments further confirmed these findings, with the Mechano Growth Factor group exhibiting increased formation of lamellar bone, more defined Haversian channels, and greater osteoid synthesis. These models also displayed better-supported vascularity and a more favorable balance in fibroblast density. Collectively, these observations suggest that Mechano Growth Factor may exert its supportive potential on bone cells by promoting osteoblast proliferation and possibly impacting differentiation through modulation of cell cycle progression and activation of the MAPK-Erk1/2 pathway.

You can find Mechano Growth Factor Peptide for sale with 99% purity, on our website (available for research use only).

NOTE: These products are intended for laboratory research use only. This peptide is not intended for personal use. Please review and adhere to our Terms and Conditions before ordering.

 

References:

1. Li C, Vu K, Hazelgrove K, Kuemmerle JF. Increased IGF-IEc expression and mechano-growth factor production in the intestinal muscle of fibrostenotic Crohn’s disease and smooth muscle hypertrophy. Am J Physiol Gastrointest Liver Physiol. 2015 Dec 1;309(11):G888-99. doi: 10.1152/ajpgi.00414.2014. Epub 2015 Oct 1. PMID: 26428636; PMCID: PMC4669353.
2. Matheny RW Jr, Nindl BC, Adamo ML. Minireview: Mechano-growth factor: a putative product of IGF-I gene expression involved in tissue repair and regeneration. Endocrinology. 2010 Mar;151(3):865-75. doi: 10.1210/en.2009-1217. Epub 2010 Feb 3. PMID: 20130113; PMCID: PMC2840678.
3. Kandalla PK, Goldspink G, Butler-Browne G, Mouly V. Mechano Growth Factor E peptide (MGF-E), derived from an isoform of IGF-1, activates human muscle progenitor cells and induces an increase in their fusion potential at different ages. Mech Ageing Dev. 2011 Apr;132(4):154-62. doi: 10.1016/j.mad.2011.02.007. Epub 2011 Feb 25. PMID: 21354439.
4. Janssen JA, Hofland LJ, Strasburger CJ, van den Dungen ES, Thevis M. Potency of Full-Length Mechano Growth Factor to Induce Maximal Activation of the IGF-I R Is Similar to Recombinant Human IGF-I at High Equimolar Concentrations. PLoS One. 2016 Mar 18;11(3):e0150453. doi: 10.1371/journal.pone.0150453. PMID: 26991004; PMCID: PMC4798685.
5. Liu X, Zeng Z, Zhao L, Chen P, Xiao W. Impaired Skeletal Muscle Regeneration Induced by Macrophage Depletion Could Be Partly Ameliorated by Mechano Growth Factor Injection. Front Physiol. 2019 May 17;10:601. doi: 10.3389/fphys.2019.00601. PMID: 31164836; PMCID: PMC6534059.
6. Doroudian G, Pinney J, Ayala P, Los T, Desai TA, Russell B. Sustained delivery of Mechano Growth Factor peptide from microrods attracts stem cells and reduces apoptosis of myocytes. Biomed Microdevices. 2014 Oct;16(5):705-15. doi: 10.1007/s10544-014-9875-z. PMID: 24908137; PMCID: PMC4418932.
7. Liu Y, Duan M, Zhang D, Xie J. The role of mechano growth factor in chondrocytes and cartilage defects: a concise review. Acta Biochim Biophys Sin (Shanghai). 2023 May 12;55(5):701-712. doi: 10.3724/abbs.2023086. PMID: 37171185; PMCID: PMC10281885.
8. Deng M, Zhang B, Wang K, Liu F, Xiao H, Zhao J, Liu P, Li Y, Lin F, Wang Y. Mechano growth factor E peptide promotes osteoblasts proliferation and bone-defect healing in rabbits. Int Orthop. 2011 Jul;35(7):1099-106. doi: 10.1007/s00264-010-1141-2. Epub 2010 Nov 6. PMID: 21057789; PMCID: PMC3167400.