Autophagy attenuates osteoarthritis in mice by inhibiting chondrocyte pyroptosis and improving subchondral bone remodeling

Authors

  • Jiangbo Yan Clinical College, Ningxia Medical University, Yinchuan, China; Orthopedics Ward 3, The General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan, China
  • Gangning Feng Clinical College, Ningxia Medical University, Yinchuan, China
  • Yong Yang Orthopedics Ward 3, The General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan, China
  • Dong Ding Hand and Ankle Department, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
  • Long Ma Orthopedics Ward 3, The General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan, China
  • Xin Zhao Orthopedics Ward 3, The General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan, China
  • Xiaolei Chen Clinical College, Ningxia Medical University, Yinchuan, China; Orthopedics Ward 3, The General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan, China
  • Hui Wang Clinical College, Ningxia Medical University, Yinchuan, China
  • Zhirong Chen Clinical College, Ningxia Medical University, Yinchuan, China; Orthopedics Ward 3, The General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan, China
  • Qunhua Jin Clinical College, Ningxia Medical University, Yinchuan, China; Orthopedics Ward 3, The General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan, China

DOI:

https://doi.org/10.17305/bjbms.2022.7677

Keywords:

Osteoarthritis, chondrocyte, autophagy, pyroptosis, subchondral bone

Abstract

Osteoarthritis (OA) is an age-related degenerative disease characterized by cartilage degeneration and abnormal bone remodeling in the subchondral bone. Autophagy maintains cellular homeostasis by self-phagocytosis. However, the underlying mechanisms of autophagy on the pathological progression of OA are still unknown. This study assessed the effects of autophagy on cartilage and subchondral bone in a mouse OA model. A mouse OA model was induced using destabilization of the medial meniscus (DMM) surgery. Assessment was performed by histomorphology, microcomputed tomography (micro-CT), immunohistochemical, immunofluorescent, and tartrate-resistant acid phosphatase (TRAP) staining. Our data revealed that autophagy can significantly delay the pathological progression of OA by increasing the thickness of hyaline cartilage and decreasing the thickness of calcified cartilage, increasing the subchondral bone volume fraction and bone mineralization density, and decreasing trabecular separation in the early stages of OA (2 weeks), whereas the opposite is true in the late stages of OA (8 weeks). Mechanistically, activation of autophagy in cartilage increased the expression of type II collagen (Col II), decreased the expression of matrix metalloproteinase 13 (MMP 13) and decreased the pyroptosis mediated by NOD-like receptor protein 3 (NLRP3) inflammasome by decreasing the expression of NLRP3, caspase-1, gasdermin D (GSDMD), and IL-1β. In the subchondral bone, activation of autophagy decreased the generation of mature osteoclasts at the early stages of OA (2 weeks) mainly by reducing the receptor activator for nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio, while it decreased osteoblastogenesis by reducing Runt-related transcription factor 2 (Runx2) expression significantly in the late stages of OA (8 weeks). In conclusion, autophagy may delay the pathological progression of OA in mice by inhibiting chondrocyte pyroptosis and improving subchondral bone remodeling.

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Autophagy attenuates osteoarthritis in mice by inhibiting chondrocyte pyroptosis and improving subchondral bone

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Published

2022-07-23

How to Cite

1.
Yan J, Feng G, Yang Y, Ding D, Ma L, Zhao X, Chen X, Wang H, Chen Z, Jin Q. Autophagy attenuates osteoarthritis in mice by inhibiting chondrocyte pyroptosis and improving subchondral bone remodeling. Bosn J of Basic Med Sci [Internet]. 2022Jul.23 [cited 2022Dec.6];. Available from: https://bjbms.org/ojs/index.php/bjbms/article/view/7677

Issue

Section

Pathology