Bone-muscle interactions

Abstract

Bone and skeletal muscle jointly govern motor function, working in coordination as anatomically adjacent organs, and collaborate with through mechanical interactions. Bone and muscle cells are both derived from common mesenchymal stem cells. Muscle tissues reportedly support fracture healing and bone repair. Common factors affect muscle and bone simultaneously, and sarcopenia and osteoporosis are complications of various diseases. Research on bone-muscle interactions has progressed in the past 15 years, and clinical evidence has confirmed that a relationship exists between sarcopenia and osteoporosis. Numerous myokines or osteokines play a role in bone-muscle interactions, and the involvement of extracellular vesicles has also been suggested. Research on bone-muscle interactions may translate into clinical applications for the treatment of sarcopenia and osteoporosis.

Keywords: Bone; Muscle; Myokine; Osteokine; Sarcopenia.

Fig. 1

Bone-muscle interactions. Skeletal muscle interacts with bone. Direct interactions through mechanical burden or local growth factors are involved in bone-muscle interactions.

Fig. 2

Various factors affect both muscle and bone. Aging, genetic factors, mechanical stress, nutrition, endocrine factors, inflammation, and systemic diseases affect muscle and bone. CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease.

Fig. 3

Osteoporosis and sarcopenia. Osteoporosis is characterized by a decrease in BMD and/or bone quality, which reduces bone strength and increases the risk of fracture. Bone quality is affected by changes in the bone microarchitecture, mineralization, bone turnover, and bone morphological changes. Sarcopenia is defined by decreases in muscle mass, muscle strength, and physical function. Osteoporosis and sarcopenia are related to each other, and osteosarcopenia is a newly proposed syndrome that describes the coexistence of osteoporosis and sarcopenia.

Fig. 4

Myokines affecting bone. Numerous myokines affect bone under physiological and pathophysiological conditions. BAIBA, β-aminoisobutyric acid; DKK-2, Dickkopf-related protein-2; FAM-5C, family with sequence similarity-5, member C; FGF-2, fibroblast growth factor-2; IGF-1, insulin-like growth factor-1; IL-6, interleukin-6; PMP-22, peripheral myelin protein-22; TGF-β, transforming growth factor-β

Fig. 5

Role of irisin in bone-muscle interactions. Exercise up-regulates the expression of irisin in muscle, whereas its expression is down-regulated by mechanical unloading, CKD (chronic kidney disease), diabetes, glucocorticoid excess, and androgen deficiency in mice. Irisin increases bone mass by promoting bone formation and inhibiting bone resorption.

Fig. 6

Roles of muscle-derived extracellular vesicles (EVs) in muscle-bone interactions. EVs released from skeletal muscle affect bone by suppressing the formation of osteoclasts and stimulating osteogenic differentiation. Mechanical stress and inflammation have an impact on bone by affecting muscle cells and then positively and negatively modulating EVs, respectively.