The Role of Irisin in Exercise-Mediated Bone Health

Abstract

Exercise training promotes physical and bone health, and is the first choice of non-drug strategies that help to improve the prognosis and complications of many chronic diseases. Irisin is a newly discovered peptide hormone that modulates energy metabolism and skeletal muscle mass. Here, we discuss the role of irisin in bone metabolism via exercise-induced mechanical forces regulation. In addition, the role of irisin in pathological bone loss and other chronic diseases is also reviewed. Notably, irisin appears to be a key determinant of bone mineral status and thus may serve as a novel biomarker for bone metabolism. Interestingly, the secretion of irisin appears to be mediated by different forms of exercise and pathological conditions such as diabetes, obesity, and inflammation. Understanding the mechanism by which irisin is regulated and how it regulates skeletal metabolism via osteoclast and osteoblast activities will be an important step toward applying new knowledge of irisin to the treatment and prevention of bone diseases such as osteolysis and other chronic disorders.

Association Between Factors Involved in Bone Remodeling (Osteoactivin and OPG) With Plasma Levels of Irisin and Meteorin-Like Protein in People With T2D and Obesity

“…It was postulated that the rise in irisin levels for an extended period of time can lead to increased bone catabolism, while its knockout can lead to bone formation (60). Nevertheless, irisin was shown to play an important role in increasing bone formation via regulating osteoblast-led bone formation (57,59,61). Interestingly, the data from the current study highlights a strong association between irisin and two factors involved in bone remodeling namely, osteoactivin and OPG.…”

“…Both Irisin and METRNL are primarily secreted by the skeletal muscles. It has been reported that irisin plays an essential role in the interaction between muscle tissue and bone metabolism, suggesting that there is a strong bonemuscle interaction (9,(55)(56)(57). Recently there has been a stronger link between irisin and bone metabolism through the identification of an integrin aV/b5 that acts as the irisin receptor on osteocytes (58).…”

Molecular targets of exercise mimetics and their natural activators

“…Irisin is a hormone-like myokine induced by exercise, and is also expressed in small amounts in bone, brain, and other tissues ( 18 , 19 ). The peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a critical regulator of exercise-induced skeletal muscle adaptation ( 20 ).…”

“…And exercise-driven upregulation of PGC-1α in muscle promotes the synthesis of fibronectin domain-containing protein 5 (FNDC5), which is subsequently cleaved to generate irisin ( 18 , 21 ). The level of irisin positively correlates with muscle mass and muscle strength ( 19 ) and injection of irisin rescues denervation-induced loss of skeletal muscle mass by enhancing satellite cell activation and reducing protein degradation ( 22 ). Also, upregulation of the PGC-1α/FNDC5/irisin pathway has been suggested to be responsible for the exercise-mediated accelerated recovery of myopathy through increasing mitochondrial fission and mitophagy ( 23 ).…”

“…The conversion of white to brown adipose tissue mediated by exercise has been reported to be through inducing irisin which stimulates the expression UCP-1, the master regulator of brown adipose tissue ( 27 ). The benefit of physical exercise on bone mineral density is widely-accepted, and irisin has been reported to play an active role between skeletal muscles and bones ( 19 ). Irisin promotes cortical bone mass and strength as well as osteoblast differentiation through regulating expression of bone-specific genes and up-stream signaling pathways ( 24 ).…”