MT-II

The mechanism most consistently proposed in the literature is angiomodulatory rather than directly mitogenic. Work from the Sikiric group reports upregulation of vascular endothelial growth factor receptor 2 with downstream activation of the Akt and endothelial nitric oxide synthase pathway, and a body of related work situates the peptide as an interacting partner of the nitric oxide system, reported as counteracting both excessive and deficient NO signalling in different injury models rather than acting in a single direction. Separate in vitro work by Chang and colleagues reported increased outgrowth from tendon explants, improved fibroblast survival under hydrogen peroxide stress and dose-dependent fibroblast migration, with FAK-paxillin signalling implicated, and a subsequent paper from the same group reported growth hormone receptor as among the most abundantly upregulated transcripts in treated tendon fibroblasts. These are proposed mechanisms drawn from animal and cell-culture models, reported here as literature and not as established pharmacology in any species.