Myostatin in the pathophysiology of skeletal muscle

Abstract

Myostatin is an endogenous, negative regulator of muscle growth determining both muscle fiber number and size. The myostatin pathway is conserved across diverse species ranging from zebrafish to humans. Experimental models of muscle growth and regeneration have implicated myostatin as an important mediator of catabolic pathways in muscle cells. Inhibition of this pathway has emerged as a promising therapy for muscle wasting. Here we discuss the recent developments and the controversies in myostatin research, focusing on the molecular and cellular mechanisms underlying the actions of myostatin on skeletal muscle and the potential therapeutic role of myostatin on muscle-related disorders.

Fig. (1)

The potential functions of myostatin in regulating satellite cells.Growth and repair of adult skeletal muscle require the action of a population of normally quiescent myogenic precursors called satellite cells (SC) which reside between the basal lamina and the plasma membrane of the myofibres. In response to muscle injury or increased muscle tension, these cells become activated, start proliferating and are responsible for the repair of damaged muscle fibres and the growth of muscle fibres. Importantly, a proportion of the progeny of the activated satellite cells does not differentiate, but withdraws from the cell cycle to replace the activated satellite cell used, in a process of self-renewal. Myostatin negatively regulates satellite cell activation and self-renewal. A possible function is that Myostatin inhibits/prevents the progression of myoblats from the G1 to S phase of the cell cycle through up-regulation of p21 and subsequent inhibition of Cdk2 activity, thus maintaining the quiescence of satellite cells. Another function is that myostatin inhibits the self-renewal of the satellite cell population through down-regulation of Pax7.