Regulation of bone health through physical exercise: Mechanisms and types

Abstract

Osteoporosis, characterized by bone mineral density reduction, bone mass loss, increased bone fragility, and propensity to fractures, is a common disease in older individuals and one of the most serious health problems worldwide. The imbalance between osteoblasts and osteoclasts results in the predominance of bone resorption and decreased bone formation. In recent years, it has been found that regular and proper exercise not only helps prevent the occurrence of osteoporosis but also adds benefits to osteoporosis therapy; accordingly, bone homeostasis is closely associated with mechanical stress and the intricate crosstalk between osteoblasts and osteoclasts. In this review, we summarize the mechanisms of exercise on osteoporosis and provide new proposals for the prevention and treatment of osteoporosis.

Keywords: PCs; Piezo1; bone mass; cytokines; exercise; irisin; osteoporosis.

Figure 1

Direct and indirect regulation mechanisms of exercise for osteoporosis. Cell surface receptors are the starting point for understanding the regulatory effects of mechanical loading, which include focal adhesions, integrins, purinergic receptors, connexin, polycystins, Piezos, Wnt signaling and sclerostin. In addition, exercise-induced regulation of bone environment also occurs through cytokines, including inflammatory factors and myokines, such as irisin. These factors affect bone remodeling collectively. Exercise promotes bone mass and sustain healthy bone, while lacking exercise results in osteoporosis and fracture.

Figure 2

Canonical Wnt signaling and sclerostin in mechanical regulation of exercise. Exercises produce mechanical stimulus and increase Wnt1. Wnt1 binds with LRP5/6, subsequently activate intercellular Dvl, resulting in release of free β-catenin and translocation into nuclei. β-cateniin binds with TEF/LEF, contributes to induction and activation of Runx2, Osx, and cyclinD1. Osteoblast differentiation and bone mass increase is activated by Wnt and inhibited by the Wnt antagonists Frizzled and sclerostin. When without mechanical stimulus bring by exercise, Wnt1 decreased and β-catenin is ubiquitinated and degraded, inducing downregulation in the expression of downstream target gene, bone mass subsequently decreased.