Fig. 7.

Summary of sclerostin role in bone and muscle crosstalk.⁴⁶) Crosstalk between bones and muscles is mediated not just by mechanical loads and activity, but also as a paracrine organ. Sclerostin is a key regulator of unloading-induced bone loss and is involved in bone mechanotransduction. Sclerostin levels will be reduced as a result of increased activity and mechanical loading. Sclerostin is a Wnt antagonist that responds to mechanical stimulation. Mechanical loading reduces sclerostin levels, which activates Wnt/β signaling. A meanwaging will result in alterations in autophagy, which will have an impact on bone and muscle. Meanwhile, a new paradigm has emerged, claiming that bone and muscle can function as an endocrine organ, secreting sclerostin, which can function as both myokines and osteokine. Reduced sclerostin levels in the bone lower osteoclast and RANKL stimulation, resulting in increased bone growth and osteoblast. On the other hand, two key wnt families play important roles in muscle: Wnt3 which acts via the canonical pathway and Wnt4 which acts via both the canonical and non-canonical pathways. Wnt3 and Wnt4 activation leads to myogenesis. Sclerostin is an effective inhibitor of both.