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Pentraxin 3 regulated by miR-224-5p modulates macrophage reprogramming and exacerbates osteoarthritis associated synovitis by targeting CD32.
Yin, Jianbin; Zeng, Hua; Fan, Kai; Xie, Haoyu; Shao, Yan; Lu, Yuheng; Zhu, Jinjian; Yao, Zihao; Liu, Liangliang; Zhang, Hongbo; Luo, Bingsheng; Wang, Xinjie; Zeng, Chun; Bai, Xiaochun; Zhang, Haiyan; Cai, Daozhang.
Afiliação
  • Yin J; Department of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
  • Zeng H; Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
  • Fan K; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.
  • Xie H; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China.
  • Shao Y; Department of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
  • Lu Y; Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
  • Zhu J; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.
  • Yao Z; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China.
  • Liu L; Department of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
  • Zhang H; Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
  • Luo B; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.
  • Wang X; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China.
  • Zeng C; Department of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
  • Bai X; Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
  • Zhang H; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.
  • Cai D; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China.
Cell Death Dis ; 13(6): 567, 2022 06 24.
Article em En | MEDLINE | ID: mdl-35739102
ABSTRACT
Emerging evidence has shown an imbalance in M1/M2 macrophage polarization to play an essential role in osteoarthritis (OA) progression. However, the underlying mechanistic basis for this polarization is unknown. RNA sequencing of OA M1-polarized macrophages found highly expressed levels of pentraxin 3 (PTX3), suggesting a role for PTX3 in OA occurrence and development. Herein, PTX3 was found to be increased in the synovium and articular cartilage of OA patients and OA mice. Intra-articular injection of PTX3 aggravated, while PTX3 neutralization reversed synovitis and cartilage degeneration. No metabolic disorder or proteoglycan loss were observed in cartilage explants when treated with PTX3 alone. However, cartilage explants exhibited an OA phenotype when treated with culture supernatants of macrophages stimulated with PTX3, suggesting that PTX3 did not have a direct effect on chondrocytes. Therefore, the OA anti-chondrogenic effects of PTX3 are primarily mediated through macrophages. Mechanistically, PTX3 was upregulated by miR-224-5p deficiency, which activated the p65/NF-κB pathway to promote M1 macrophage polarization by targeting CD32. CD32 was expressed by macrophages, that when stimulated with PTX3, secreted abundant pro-inflammation cytokines that induced severe articular cartilage damage. The paracrine interaction between macrophages and chondrocytes produced a feedback loop that enhanced synovitis and cartilage damage. The findings of this study identified a functional pathway important to OA development. Blockade of this pathway and PTX3 may prevent and treat OA.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoartrite / Sinovite / Proteína C-Reativa / Componente Amiloide P Sérico / MicroRNAs Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Cell Death Dis Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoartrite / Sinovite / Proteína C-Reativa / Componente Amiloide P Sérico / MicroRNAs Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Cell Death Dis Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China