School of Pharmacy, University College Cork, Cork, Ireland.
Departments of Medicine and Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Pharmacol Res. 2017 Nov;125(Pt B):232-245. doi: 10.1016/j.phrs.2017.08.013. Epub 2017 Sep 22.
The lipid mediator sphingosine 1-phosphate (S1P) affects cellular functions in most systems. Interest in its therapeutic potential has increased following the discovery of its G protein-coupled receptors and the recent availability of agents that can be safely administered in humans. Although the role of S1P in bone biology has been the focus of much less research than its role in the nervous, cardiovascular and immune systems, it is becoming clear that this lipid influences many of the functions, pathways and cell types that play a key role in bone maintenance and repair. Indeed, S1P is implicated in many osteogenesis-related processes including stem cell recruitment and subsequent differentiation, differentiation and survival of osteoblasts, and coupling of the latter cell type with osteoclasts. In addition, S1P's role in promoting angiogenesis is well-established. The pleiotropic effects of S1P on bone and blood vessels have significant potential therapeutic implications, as current therapeutic approaches for critical bone defects show significant limitations. Because of the complex effects of S1P on bone, the pharmacology of S1P-like agents and their physico-chemical properties, it is likely that therapeutic delivery of S1P agents will offer significant advantages compared to larger molecular weight factors. Hence, it is important to explore novel methods of utilizing S1P agents therapeutically, and improve our understanding of how S1P and its receptors modulate bone physiology and repair.
脂质介质 1-磷酸鞘氨醇（S1P）影响大多数系统中的细胞功能。在发现其 G 蛋白偶联受体和最近可安全用于人体的药物后，人们对其治疗潜力的兴趣大增。尽管 S1P 在骨生物学中的作用的研究远少于其在神经系统、心血管系统和免疫系统中的作用，但很明显，这种脂质影响许多在维持和修复骨骼中起关键作用的功能、途径和细胞类型。事实上，S1P 参与许多与成骨相关的过程，包括干细胞募集和随后的分化、成骨细胞的分化和存活，以及后者与破骨细胞的偶联。此外，S1P 在促进血管生成中的作用已得到充分证实。S1P 对骨骼和血管的多效作用具有重要的潜在治疗意义，因为目前针对临界骨缺损的治疗方法存在显著局限性。由于 S1P 对骨骼的复杂影响、S1P 样药物的药理学及其理化性质，与分子量较大的因子相比，S1P 药物的治疗性传递可能具有显著优势。因此，探索利用 S1P 药物进行治疗的新方法，以及提高我们对 S1P 及其受体如何调节骨骼生理学和修复的理解非常重要。
