The role of sphingosine-1-phosphate in bone remodeling and osteoporosis

Osteoporosis is a systemic bone disease that affects more than 200 million people worldwide and is caused by the disruption of the equilibrium between osteoclastic bone resorption and osteoblastic bone formation. Sphingosine-1-phosphate(S1 P) is a natural,bioactive sphingolipid that has been shown to play a major role in cardiovascular and immunological pathologies by regulating biological and cellular processes, including migration, differentiation, proliferation and survival. Recent studies also suggest a central role for S1 P in bone diseases, including osteoporosis; however, the effects of S1 P, particularly in bone metabolism, remain to be further elucidated. In this review, we summarize the available literature on the role of S1 P in bone metabolism with a focus on osteoporosis. On the cellular level, S1 P acts as an osteoclast-osteoblast coupling factor to promote osteoblast proliferation and bone formation. Moreover, the recruitment of osteoclast precursors to resorption sites is regulated by the interplay of S1 P gradients and S1 P receptor expression. From a clinical perspective, increasing evidence suggests that systemically elevated S1 P blood levels may serve as an independent risk factor for osteoporosis-related fractures. Taken together, S1 P signaling is a potential therapeutic target and may serve as a novel biomarker in patients with systemic bone disease.