Endogenous parathyroid hormone (PTH) signals through osteoblasts via RANKL during fracture healing to affect osteoclasts
Endogenous parathyroid hormone (PTH) signals through osteoblasts via RANKL during fracture healing to affect osteoclasts
复制标题
骨折愈合过程中内源性甲状旁腺激素 (PTH) 通过 RANKL 通过成骨细胞发出信号影响破骨细胞
DOI：
10.1016/j.bbrc.2020.02.177
复制
发表时间：
2020-05-14
影响因子：
3.1
通讯作者：
Yin, Guo-Yong
中科院分区：
文献类型：
--
作者：
Sun, Peng;Wang, Ming;Yin, Guo-Yong
目的：目的：探讨内源性甲状旁腺激素（PTH）缺乏对骨折愈合过程中破骨细胞的影响及其机制。结果：在本研究中，我们发现在PTH敲除（KO）小鼠中RANKL和CK的表达低于野生型（WT）小鼠。破骨细胞体外培养结果显示，在相同刺激下，PTH WT小鼠和PTH KO小鼠破骨细胞数量和骨吸收区面积无统计学差异。我们发现高浓度的RANKL可以促进破骨细胞的数量和活性。在体外诱导成骨细胞后，PTH WT组表达的RANKL蛋白和mRNA高于PTH KO组。结论：骨折愈合过程中，内源性PTH缺乏可通过降低成骨细胞RANKL的表达而影响破骨细胞的活性。(C)2020爱思唯尔公司All rights reserved.
Aim: To investigate the effect of endogenous PTH deficiency on osteoclasts during fracture healing and its mechanism.Methods: A femoral fracture model was used to determine the role of endogenous PTH in fracture healing. Immunohistochemistry, qPCR, and Western blot were used to determine the potential functions and mechanisms of endogenous PTH.Result: In this study, we found that expression of RANKL and CK was lower in PTH knockout (KO) mice than in wild type (WT) mice. In vitro culture of osteoclasts showed that under the same stimulation, there was no statistical difference in the number of osteoclasts and the area of bone resorption areas in PTH WT mice and PTH KO mice. We found that a high concentration of RANKL could promote the number and activity of osteoclasts. Upon induction of osteoblasts in vitro, those from the PTH WT group expressed higher RANKL protein and mRNA than those from the PTH KO group. Lastly, we confirmed that the PI3K/AKT/STAT5 pathway promotes RANKL increase from osteoblasts.Conclusion: During fracture healing, endogenous PTH deficiency can affect osteoclast activity by reducing RANKL expression in osteoblasts. (C) 2020 Elsevier Inc. All rights reserved.