A role for myokines in muscle-bone interactions

Abstract

This review presents the hypothesis that muscle is a source of secreted factors (myokines) that can influence bone mass in both positive and negative ways. Growth factor secretion by muscle may therefore be one pathway through which mechanical signals are transduced biologically.

Figures

Figure 1

A. Cross-section of a proximal limb segment showing skeletal muscle surrounding bone. Muscle injury with exercise releases FGF-2 from wounded myocytes into the circulation, and skeletal myocytes also secrete IGF-1 into the bloodstream in addition to liver-derived IGF-1. Myofiber hypertrophy is though to increase IGF-1 expression and secretion. B. Enlarged section of the muscle-bone interface, showing osteoprogenitor cells lining the periosteal and endosteal surfaces of cortical bone. Circulating muscle-derived FGF-2 and IGF-1 is delivered to endosteal bone-forming cells lining the marrow cavity, cells that express receptors for FGF-2 (FGF-R2) and IGF-1 (IGF-1R). Periosteal bone forming cells directly adjacent to myocytes also express these receptors and also receive local, muscle-derived IGF-1 and FGF-2. Hence, muscle derived growth factors can stimulate their receptors in osteoprogenitor cells and osteoblasts through both endocrine and paracrine pathways.

Figure 2

Muscle is also a source of the anti-osteogenic factor myostatin (Mstn, or GDF-8). Conditions such as disuse atrophy due to weightlessness, bedrest, and unloading, or conditions associated with stress such as infection, trauma, or burns, elevate circulating glucocorticoids. These glucocorticoids stimulate myostatin expression and myostatin secretion in muscle, which in turn contributes to muscle wasting but also acts to inhibit bone formation directly. Myostatin inhibitors can enhance muscle mass and also increase bone formation in vivo.