Semaphorin 3A on Osteoporosis: An Overreview of the Literature

Semaphorin 3A (Sema3A) is a signaling protein that has attracted increasing attention in recent years for its important role in regulating bone metabolism. In this review, we searched different databases with various combinations of keywords to analyze the effects of Sema3A on osteoporosis. Sema3A promotes bone formation and inhibits bone resorption by directly affecting the osteoblast and osteoclast or indirectly targeting the nervous system. The sympathetic nervous system may be the main link between the central nervous system and bone metabolism for Sema3A. In the peripheral nervous system, Sema3A may improve bone quality via sensory nervous innervation. In addition, estrogen is found to regulate Sema3A levels to improve bone homeostasis. Lots of Sema3A agonists have been documented to exhibit anti-osteoporotic potential in preclinical investigations. Therefore, Sema3A can be considered a novel therapeutic target for preserving bone mass, highlighting an alternative strategy for the development of anti-osteoporosis drugs.