Sclerostin's role in bone-muscle crosstalk and osteoporosis pathogenesis

Abstract

This review examines sclerostin, a critical regulator of Wnt signaling, focusing on its role in bone homeostasis and its emerging involvement in muscle-bone crosstalk. It examines the regulatory influence of hormones, mechanical stress, and myokines on sclerostin expression under both physiological and pathological conditions. Recent advances underscore sclerostin's role in osteoporosis pathogenesis and its involvement in bone remodeling, while also revealing its emerging significance in muscle-bone communication. Despite these insights, the underlying mechanisms of its regulation remain incompletely understood. By consolidating recent research, this review provides a comprehensive perspective on sclerostin's multifaceted roles and their implications for bone and muscle health.

Keywords: Crosstalk; Molecular interaction; Myokines; Osteoporosis; Regulators; Sclerostin.

Fig. 1

Mechanical loading promotes bone remodeling by upregulating Osteoprotegerin (OPG) and downregulating sclerostin, which, in turn, leads to reduced osteoclast formation (osteoclastogenesis).

Fig. 2

Parathyroid hormones promote osteogenesis by downregulating sclerostin and promoting Wnt signaling.

Fig. 3

Schematic representation of the regulatory role of estrogen in bone remodeling.