Role of Canonical and Non-Canonical Sphingolipids and their Metabolic Enzymes in Bone Health

This review summarizes the recently published scientific evidence regarding the role of enzymes engaged in de novo anabolic biosynthesis, catabolic, and salvage pathways of ceramide bioactive sphingolipids in bone dynamics and skeletal health.

Ceramides are precursors for bioactive sphingolipids, including sphingosine, sphingosine-1-phosphate, and others. Studies of bone metabolism and bone-related cells demonstrated that ceramide and sphingosine-1-phosphate control levels of bone remodeling and resorption generated by osteoblasts and osteoclasts. Multiple published studies demonstrated the critical role of enzymes in regulating the ceramide/sphingosine-1-phosphate ratio relative to bone physiology and the promotion of inflammatory osteolysis. Accordingly, emerging evidence suggests that targeting sphingolipid metabolism has the potential to alleviate inflammatory osteolysis and accelerate bone regeneration. Therefore, this study aimed to discuss current knowledge about crosstalk between sphingolipids and their metabolic enzymes within osteoclast and osteoblast coupling in bone remodeling and pathogenic osteolysis. This review highlights the complexity of de novo sphingolipid biosynthesis and knowledge gaps in bone physiology and pathology. We also discuss the importance of canonical and non-canonical mammalian and bacterial-derived sphingolipids relative to bone health.