Effects of Muscles on Bone Metabolism—with a Focus on Myokines

Abstract

Skeletal muscles and bones, the largest tissues in the body of a non-obese person, comprise the musculoskeletal system, which allows mobility and protects internal organs. Although muscles and bones are intimately related throughout life, observations during development and aging and in human and animal disuse models have revealed the synchronization of tissue mass such that muscle phenotype changes precede alterations in bone mineral density and strength. This review discussed that mechanical forces, which have been the traditional research focus, are not the only mechanism by which muscle-derived signals may affect bone metabolism and emphasized the significance of skeletal muscles as an endocrine organ that secretes bone-regulatory factors. Consequently, both mechanical and biochemical aspects should be considered to fully understand muscle–bone crosstalk. This review also suggested that specific myokines could be ideal therapeutic targets for osteoporosis to both increase bone formation and reduce bone resorption; moreover, these myokines could also be potential circulating biomarkers to predict musculoskeletal health.

Physical performance and negative events in very old adults: a longitudinal study examining the ilSIRENTE cohort

“…Besides its role in force generation, the skeletal muscle is an endocrine organ that communicates with other bodily systems through myokines, molecules with pluripotent effects that are synthesized and released by active skeletal myocytes [47][48][49]. Myokines influence important physiological processes at musculoskeletal, metabolic, neural, vascular, and immunological levels [49][50][51][52]. A reduced expression of several myokines has been found in muscle biopsies from critically ill patients [53], in whom a lower FNDC5/irisin ratio (precursor/myokine) has been independently associated with mortality.…”

Sarcopenia as the Mobility Phenotype of Aging: Clinical Implications

“…[51] Additionally, various drugs that block the myostatin-activin pathway, an upstream pathway of muscle atrophy, have been developed to inhibit muscle protein breakdown in situations of anabolic resistance. [52] Studies in humans have established clinical evidence showing that older adults and individuals with chronic diseases require greater protein intake to overcome anabolic resistance. [46]…”

The critical impact of traumatic muscle loss on fracture healing: Basic science and clinical aspects

“…32,33 2.2 | Muscle as a "secondary periosteum" for bone regeneration Over the past few years, several studies have demonstrated that the surrounding muscle plays a key role in inducing osteogenesis. 9,[34][35][36] Historically, muscle has been viewed as a common site for heterotopic ossification that occurs either because of physical trauma or genetic disorders. 37,38 However, in recalcitrant fracture healing or distraction osteogenesis, bone formation commonly occurs nearby the surrounding muscle tissue.…”

“…Over the past few years, several studies have demonstrated that the surrounding muscle plays a key role in inducing osteogenesis 9,34–36 . Historically, muscle has been viewed as a common site for heterotopic ossification that occurs either because of physical trauma or genetic disorders 37,38 .…”