Role of inhibition of osteogenesis function by Sema4D/Plexin-B1 signaling pathway in skeletal fluorosis in vitro
Role of inhibition of osteogenesis function by Sema4D/Plexin-B1 signaling pathway in skeletal fluorosis in vitro
复制标题
Sema4D/Plexin-B1信号通路抑制成骨功能在体外氟骨症中的作用
DOI：
10.1007/s11596-015-1495-1
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发表时间：
2015-10-01
影响因子：
--
通讯作者：
Liu, Yun
中科院分区：
文献类型：
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作者：
Liu, Xiao-li;Song, Jing;Liu, Yun
氟骨症是一种因长期接触氟而引起的以广泛性骨质增生为主要表现的慢性代谢性骨病。氟骨症可引起关节疼痛、关节僵硬、骨骼畸形等一系列异常改变。破骨细胞通过Sema 4D/Plexin-B1信号通路调控成骨细胞的分化和成熟。此外，破骨细胞的分化和成熟是由成骨细胞通过RANKL/RANK/OPG途径进行的。这两个过程形成一个反馈回路，是氟骨症发病的关键环节。本研究通过建立成骨细胞-破骨细胞共培养模型，探讨氟骨症的发病机制。随着氟浓度的增加，Sema 4D的表达水平逐渐降低，TGF-β1的表达水平逐渐升高。OPG/RANKL mRNA水平逐渐升高。在此基础上，氟对Sema 4D/Plexin-B1/RhoA/ROCK信号通路的抑制促进了TGF-β1的表达，激活了成骨细胞的增殖。此外，成骨细胞分泌的骨保护素（OPG）被氟上调。OPG与RANKL的竞争结合增强，RANKL与RANK的结合受阻。破骨细胞分化成熟受到抑制，骨吸收减弱，导致氟骨症。
Skeletal fluorosis is a chronically metabolic bone disease with extensive hyperostosis osteosclerosis caused by long time exposure to fluoride. Skeletal fluorosis brings about a series of abnormal changes of the extremity, such as joint pain, joint stiffness, bone deformity, etc. Differentiation and maturation of osteoblasts were regulated by osteoclasts via Sema4D/Plexin-B1 signaling pathway. Furthermore, the differentiation and maturation of osteoclasts are conducted by osteoblasts via RANKL/RANK/OPG pathway. Both of these processes form a feedback circuit which is a key link in skeletal fluorosis. In this study, an osteoblast-osteoclast co-culture model in vitro was developed to illustrate the mechanism of skeletal fluorosis. With the increase of fluoride concentration, the expression level of Sema4D was decreased and TGF-β1 was increased continuously. OPG/RANKL mRNA level, however, increased gradually. On the basis of that, the inhibition of Sema4D/Plexin-B1/RhoA/ROCK signaling pathway caused by fluoride promoted the level of TGF-β1 and activated the proliferation of osteoblasts. In addition, osteroprotegerin (OPG) secreted by osteoblasts was up-regulated by fluoride. The competitive combination of OPG and RANKL was strengthened and the combination of RANKL and RANK was hindered. And then the differentiation and maturation of osteoclasts were inhibited, and bone absorption was weakened, leading to skeletal fluorosis.