Targeting S1PRs as a Therapeutic Strategy for Inflammatory Bone Loss Diseases-Beyond Regulating S1P Signaling.
Targeting S1PRs as a Therapeutic Strategy for Inflammatory Bone Loss Diseases-Beyond Regulating S1P Signaling.
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DOI：
10.3390/ijms22094411
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发表时间：
2021-04-23
影响因子：
5.6
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Yu H
鞘氨醇-1-磷酸受体（S1PRs）作为G蛋白偶联受体，近年来因其在炎症性骨质流失疾病中的调节作用而受到关注。值得注意的是，在小鼠研究中，通过S1PR2的特异性抑制剂JTE013抑制S1PR2，可以减轻RANKL引起的骨质疏松症，减轻口腔细菌炎症引起的牙周牙槽骨丢失。用多种S1PRs调节剂FTY720治疗小鼠也能抑制卵巢切除术诱导的骨质疏松症、胶原或佐剂诱导的关节炎和根尖牙周炎。然而，大多数先前的研究和综述主要集中在S1PRs如何操纵S1P信号通路，从而影响各种疾病。在这篇综述中，我们总结了JTE013和FTY720在调节炎症细胞因子释放、细胞趋化和破骨细胞生成，进而影响炎症性骨质流失疾病中的潜在机制。本研究组和其他实验室的研究表明，S1PRs不仅控制S1P信号，还调节其他刺激诱导的信号通路，包括细菌、脂多糖（LPS）、胆酸、核因子κB配体受体激活剂（RANKL）、IL-6和维生素d。JTE013和FTY720通过减少炎症细胞因子和趋化因子的产生来减轻炎症性骨质流失。降低炎症细胞从血液循环到骨骼和软组织的趋化性，抑制rankl诱导的破骨细胞形成。
As G protein coupled receptors, sphingosine-1-phosphate receptors (S1PRs) have recently gained attention for their role in modulating inflammatory bone loss diseases. Notably, in murine studies inhibiting S1PR2 by its specific inhibitor, JTE013, alleviated osteoporosis induced by RANKL and attenuated periodontal alveolar bone loss induced by oral bacterial inflammation. Treatment with a multiple S1PRs modulator, FTY720, also suppressed ovariectomy-induced osteoporosis, collagen or adjuvant-induced arthritis, and apical periodontitis in mice. However, most previous studies and reviews have focused mainly on how S1PRs manipulate S1P signaling pathways, subsequently affecting various diseases. In this review, we summarize the underlying mechanisms associated with JTE013 and FTY720 in modulating inflammatory cytokine release, cell chemotaxis, and osteoclastogenesis, subsequently influencing inflammatory bone loss diseases. Studies from our group and from other labs indicate that S1PRs not only control S1P signaling, they also regulate signaling pathways induced by other stimuli, including bacteria, lipopolysaccharide (LPS), bile acid, receptor activator of nuclear factor κB ligand (RANKL), IL-6, and vitamin D. JTE013 and FTY720 alleviate inflammatory bone loss by decreasing the production of inflammatory cytokines and chemokines, reducing chemotaxis of inflammatory cells from blood circulation to bone and soft tissues, and suppressing RANKL-induced osteoclast formation.
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影响因子：
4.8
作者：
Brinkmann, V;Davis, MD;Lynch, KR
通讯作者：
Lynch, KR
DOI：
10.1084/jem.20101474
发表时间：
2010-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
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影响因子：
4
作者：
Kikuta, Junichi;Iwai, Kaori;Ishii, Masaru
通讯作者：
Ishii, Masaru
影响因子：
4.3
作者：
Baum, Rebecca;Gravallese, Ellen M.
通讯作者：
Gravallese, Ellen M.
影响因子：
6
作者：
Hsu, Li-Chien;Reddy, Sakamuri, V;Yu, Hong
通讯作者：
Yu, Hong