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
  • 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: [email protected].
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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