Department of Orthopedics, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, 223300, China.
Department of Plastic and Burn Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
Biochem Biophys Res Commun. 2020 May 14;525(4):850-856. doi: 10.1016/j.bbrc.2020.02.177. Epub 2020 Mar 10.
To investigate the effect of endogenous PTH deficiency on osteoclasts during fracture healing and its mechanism.
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.
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.
During fracture healing, endogenous PTH deficiency can affect osteoclast activity by reducing RANKL expression in osteoblasts.
研究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。
采用股骨骨折模型来确定内源性 PTH 在骨折愈合中的作用。采用免疫组织化学、qPCR 和 Western blot 来确定内源性 PTH 的潜在功能和机制。
在这项研究中，我们发现 PTH 基因敲除（KO）小鼠的 RANKL 和 CK 表达低于野生型（WT）小鼠。体外培养破骨细胞显示，在相同刺激下，PTH WT 小鼠和 PTH KO 小鼠的破骨细胞数量和骨吸收面积无统计学差异。我们发现高浓度的 RANKL 可促进破骨细胞的数量和活性。体外诱导成骨细胞后，PTH WT 组的 RANKL 蛋白和 mRNA 表达均高于 PTH KO 组。最后，我们证实 PI3K/AKT/STAT5 通路可促进成骨细胞中 RANKL 的增加。
在骨折愈合过程中，内源性 PTH 缺乏可通过降低成骨细胞中 RANKL 的表达来影响破骨细胞的活性。
