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Sphingosine 1-phosphate signaling in bone remodeling: multifaceted roles and therapeutic potential

机译：鞘氨醇1-磷酸骨质信号传导：多方面的角色和治疗潜力

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Introduction: Sphingolipids belong to a complex class of lipid molecules that are crucially involved in the regulation of important biological processes including proliferation, migration and apoptosis. Given the significant progress made in understanding the sphingolipid pathobiology of several diseases, sphingolipid-related checkpoints emerge as attractive targets. Recent data indicate the multifaceted contribution of the sphingolipid machinery to osteoclast - osteoblast crosstalk, representing one of the pivotal interactions underlying bone homeostasis. Imbalances in the interplay of osteoblasts and osteoclasts might lead to bone-related diseases such as osteoporosis, rheumatoid arthritis, and bone metastases.Areas covered: We summarize and analyze the progress made in bone research in the context of the current knowledge of sphingolipid-related mechanisms regulating bone remodeling. Particular emphasis was given to bioactive sphingosine 1-phosphate (S1P) and S1P receptors (S1PRs). Moreover, the mechanisms of how dysregulations of this machinery cause bone diseases, are covered.Expert opinion: In the context of bone diseases, pharmacological interference with sphingolipid machinery may lead to novel directions in therapeutic strategies. Implementation of knowledge derived from in vivo animal models and in vitro studies using pharmacological agents to manipulate the S1P/S1PRs axes suggests S1PR2 and S1PR3 as potential drug targets, particularly in conjunction with technology for local drug delivery.
机译：介绍：鞘脂属属于一类复杂的脂质分子，该分子至关重要地参与了重要的生物方法，包括增殖，迁移和细胞凋亡。鉴于了解几种疾病的鞘脂病病病变学，鞘脂相关的检查点赋予了显着的进展，作为有吸引力的目标。最近的数据表明鞘脂机械对破骨细胞 - 成骨细胞串扰的多方面贡献，代表骨稳态下的枢转相互作用之一。成骨细胞和破骨细胞的相互作用可能导致骨质疏松症，类风湿性关节炎和骨转移等骨相关疾病。覆盖：我们总结并分析了在目前鞘脂相关的背景下的骨骼研究进展调节骨质重塑的机制。特别强调生物活性鞘氨酸1-磷酸（S1P）和S1P受体（S1PRS）。此外，涵盖了这种机制的失调引起骨病的机制.Pert意见：在骨病的背景下，与鞘脂机械的药理学干扰可能导致治疗策略的新方向。实施来自体内动物模型的知识和使用药理学试剂进行操纵S1P / S1PRS轴的体外研究表明S1PR2和S1PR3作为潜在的药物靶标，特别是与局部药物递送的技术结合。

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