2. Academic Validation
  3. Chondrocyte apoptosis in temporomandibular joint osteoarthritis promotes bone resorption by enhancing chemotaxis of osteoclast precursors

Chondrocyte apoptosis in temporomandibular joint osteoarthritis promotes bone resorption by enhancing chemotaxis of osteoclast precursors

  • Osteoarthritis Cartilage. 2022 Aug;30(8):1140-1153. 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 3
Affiliations

Affiliations

  • 1 Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China; National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China; Beijing Key Laboratory of Digital Stomatology, 22# Zhongguancun South Avenue, Haidian District, Beijing, 100081, China.
  • 2 Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China; National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China; Beijing Key Laboratory of Digital Stomatology, 22# Zhongguancun South Avenue, Haidian District, Beijing, 100081, China; Center for Temporomandibular Disorders and Orofacial Pain, Peking University School and Hospital of Stomatology, Haidian District, Beijing, China; Central Laboratory, Peking University School and Hospital of Stomatology, Haidian District, Beijing, China.
  • 3 Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China; National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China; Beijing Key Laboratory of Digital Stomatology, 22# Zhongguancun South Avenue, Haidian District, Beijing, 100081, China. Electronic address: wangxuedong@bjmu.edu.cn.
PMID: 35513247 DOI: 10.1016/j.joca.2022.04.002
Abstract

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.

Keywords

Apoptosis; Bone loss; Cartilage; Chemokines; Temporomandibular disorders (TMD).

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