The Role of Prostaglandin F_2α in Skeletal Muscle Regeneration

Abstract

W hen hormones that mediate the development of skeletal muscle strength and hypertrophy are considered, anabolic steroids, growth hormone, and insulin-like growth factor-1 typically receive much attention. However, as the study of exercise endocrinology has expanded, roles for lesser known chemical messengers in anabolic processes have been discovered. Prostaglandin F2α (PGF2α) is one such hormone, described as an endogenously-produced growth factor. 1, 2 PGF2α is a member of the prostaglandin family of eicosanoid hormones. Prostaglandins have dual roles in regeneration and inflammation, but it is their activities in inflammation that make them the primary target of cyclooxygenase (COX)inhibitor drugs (Table 1). Indeed, much of the research that seeks to elucidate the roles of prostaglandins in skeletal muscle regeneration does so through suppression of its production with COX inhibitors. Prostaglandins have pleiotropic effects in a range of cell and tissue types. 1 Prostaglandins sensitize nociceptors in the pain response (PGE2) 3 and contribute to vasodilation and control of local blood flow control during exercise (PGE2 and PGI2). 4-6 In regards to roles in regeneration, the COX-pathway and its metabolites, specifically prostaglandins E and F, have been shown to stimulate in vitro and in vivo satellite cell proliferation, differentiation, fusion, myonuclear accretion, and mixed muscle protein synthesis in both human and animal models of injury. 1, 2, 7-17 The purpose of this article is to present literature describing roles for the COX-metabolite PGF2α in regenerative processes in skeletal muscle. With PGF2α activities inferred through consequences of its suppression with COX-inhibitors, some discussion of these drugs will also be provided, as they themselves have been the focus of much research. Due to the fact prostaglandins are induced by inflammation, various techniques have been employed throughout the body of research to elicit inflammation. Pathophysiological differences between contraction-induced injury and those resulting from strains, bruises, and lacerations must be acknowledged, as it is possible these differences account for contradictory findings between some human and animal research. Studies using non-exercise models of injury are included in this manuscript in light of the fact that COXinhibitors are often used to ameliorate pain associated musculoskeletal injuries aside from exercise. Considering the relative ease with which COX-inhibiting drugs can be procured and their use for maladies ranging from delayedonset muscle soreness to arthritis and headaches, awareness of the potential consequences of prostaglandin suppression are important to many individuals, including athletes,

Inhibition of COX1/2 alters the host response and reduces ECM scaffold mediated constructive tissue remodeling in a rodent model of skeletal muscle injury

“…Previous studies utilizing knockout animals or small molecule inhibitors have described a vital role of COX2 activity in endogenous skeletal muscle repair / regeneration 26,27,29-34,61-64,63,65 . While this detrimental effect of NSAIDs on endogenous skeletal muscle repair is well described, little is known about the effect of NSAIDs on ECM scaffold mediated skeletal muscle repair/constructive remodeling.…”