Chondrocyte apoptosis in temporomandibular joint osteoarthritis promotes bone resorption by enhancing chemotaxis of osteoclast precursors,Osteoarthritis and Cartilage

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Chondrocyte apoptosis in temporomandibular joint osteoarthritis promotes bone resorption by enhancing chemotaxis of osteoclast precursors
Osteoarthritis and Cartilage ( IF 7.2 ) Pub Date : 2022-05-02 , DOI: 10.1016/j.joca.2022.04.002
Y N Guo ₁ , S J Cui ₁ , Y J Tian ₁ , N R Zhao ₁ , Y D Zhang ₁ , Y H Gan ₂ , Y H Zhou ₁ , X D Wang ₁

Affiliation

Objective

This study aimed to explore the effect and mechanism of chondrocyte apoptosis on the chemotaxis of osteoclast precursors (OCPs) during bone destruction.

Design

The relationship between cartilage and bone destruction was verified with a rat temporomandibular joint osteoarthritis (TMJOA) model. The pan-caspase inhibitor Z-VAD-FMK (ZVAD) was applied to confirm the chemotactic effect of chondrocyte apoptosis on OCPs. Synthesis and release of the key chemokine CX3CL1 in apoptotic and non-apoptotic chondrocytes was assessed with IHC, IF, WB, and ELISA. The function of CX3CL1-CX3CR1 axis in the chemotaxis of OCPs was examined by CX3XR1 inhibitor AZD8797 (AZD) and si-CX3CL1. The regulatory effect of p38 MAPK on CX3CL1 release was verified by p38 inhibitor PH-797804.

Results

A temporal and spatial association between cartilage degradation and bone resorption was found in the TMJOA model. The caspase-dependent chondrocyte apoptosis promoted chemotaxis of OCPs, which can be restrained by ZVAD. CX3CL1 was significantly upregulated when chondrocytes underwent apoptosis, and it played a critical role in the recruitment of OCPs, blockage of CX3CL1-CX3CR1 axis resulted in less bone resorption in TMJOA. P38 MAPK was activated in apoptotic chondrocytes, and had a regulatory effect on the synthesis and release of CX3CL1. After inhibition of p38 by PH-797804, the chemotactic effect of apoptotic chondrocytes on OCPs was limited.

Conclusions

This study indicates that apoptosis of chondrocytes in TMJOA enhances chemotaxis of OCPs toward osteoclast precursors through upregulation of the p38-CX3CL1 axis, thereby promoting the activation of local osteoclasts.

中文翻译：

颞下颌关节骨关节炎中的软骨细胞凋亡通过增强破骨细胞前体的趋化性促进骨吸收

客观的

本研究旨在探讨软骨细胞凋亡对骨破坏过程中破骨细胞前体（OCPs）趋化性的影响及机制。

设计

用大鼠颞下颌关节骨关节炎（TMJOA）模型验证了软骨和骨破坏之间的关系。应用泛半胱天冬酶抑制剂 Z-VAD-FMK (ZVAD) 确认软骨细胞凋亡对 OCP 的趋化作用。用 IHC、IF、WB 和 ELISA 评估凋亡和非凋亡软骨细胞中关键趋化因子 CX3CL1 的合成和释放。通过 CX3XR1 抑制剂 AZD8797 (AZD) 和 si-CX3CL1 检查 CX3CL1-CX3CR1 轴在 OCP 趋化性中的功能。p38 MAPK 对 CX3CL1 释放的调节作用通过 p38 抑制剂 PH-797804 得到验证。

结果

在 TMJOA 模型中发现了软骨退化和骨吸收之间的时间和空间关联。半胱天冬酶依赖性软骨细胞凋亡促进了 OCPs 的趋化性，这可以被 ZVAD 抑制。当软骨细胞发生凋亡时，CX3CL1 显着上调，它在 OCP 的募集中起关键作用，CX3CL1-CX3CR1 轴的阻断导致 TMJOA 中的骨吸收减少。P38 MAPK 在凋亡的软骨细胞中被激活，对 CX3CL1 的合成和释放具有调节作用。PH-797804 抑制 p38 后，凋亡软骨细胞对 OCP 的趋化作用受到限制。