Muscle–bone interactions: movement in the field of mechano–humoral coupling of muscle and bone

Abstract

Cyclical, mechanical loading of bone by skeletal muscle is widely recognized as a critical determinant of bone structure and mass. A growing body of evidence indicates that substances released from skeletal muscle into the bloodstream also regulate bone mass and metabolism. In this commentary, we discuss the status of research in the area of humoral regulation of bone mass by the skeletal muscle secretome, with an emphasis on the roles of myostatin, irisin, interleukin-6, and exosomes. The interplay between muscle, bone, and other modulators of bone mass, including circadian rhythm and sympathetic tone, is also discussed.

Myokines in skeletal muscle physiology and metabolism: Recent advances and future perspectives

“…2,5,22,28,45,46 MSTN mRNA and protein levels are reported to be increased in muscle and adipose tissues of leptin-deficient obese mice as well as in wild-type mice fed a high-fat diet (HFD). Recent studies suggest that MSTN is a key regulator of whole-body metabolism, and consequently, is associated with the development of obesity, insulin resistance and type 2 diabetes mellitus (T2DM).…”

“…1,2 For example, skeletal muscle possesses a remarkable ability to adapt to various physiologic conditions such as chronic disuse or exercise and bone mass follows muscle mass with unloading conditions such as bed rest, spaceflight or exercise. 1,2 For example, skeletal muscle possesses a remarkable ability to adapt to various physiologic conditions such as chronic disuse or exercise and bone mass follows muscle mass with unloading conditions such as bed rest, spaceflight or exercise.…”

“…1,[4][5][6] A multitude of studies have demonstrated that myokines can regulate physiological and metabolic pathways in other tissues. 1,2,5,7,8 The diverse and growing repertoire of myokines provides the basis for crosstalk between skeletal muscle and other organs, such as adipose tissue, bone, liver, pancreas, kidney and brain. These molecules exert an effect, positive or negative, on muscle function and overall metabolism and include: myostatin (MSTN), the small organic acid β-aminoisobutyric acid (BAIBA), meteorin-like (METRNL), myonectin, various interleukins (IL-6, IL-8, IL-7 and IL-15), irisin, fibroblast growth factor 21 (FGF21), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), leukaemia inhibitory factor (LIF) and follistatin-like protein-1 (FSTL-1).…”

“…[16][17][18] The rising prevalence of insulin resistance in the general population highlights the need for a better understanding of its pathogenesis. 2,3,21,[25][26][27] One of the most intriguing biological activities of myokines is their ability to modulate insulin action and metabolism of specific cells which is almost certainly of significant biomedical importance. [19][20][21][22] While the muscle responds directly to insulin by translocation of GLUT4 to the sarcoplasmic membrane, myokines likewise influence whole-body metabolism of glucose and lipids, as they have been repeatedly shown to act on adipose, liver, pancreas and intestine tissues.…”

“…Skeletal muscle is one of the main targets of insulin because it is responsible for more than 60% of insulinstimulated clearance of glucose from the circulation; of note, muscle is one of the first tissues to develop insulin resistance and importantly, insulin action is greatly influenced by physical activity. 1,2,5,7,8 [19][20][21][22][23][24] As described in more detail below, over 100 myokines have been identified by proteomics approaches and more than 250 putative myokines were reported based on GWAS and transcriptomics analyses.…”