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CD73 inhibits titanium particle-associated aseptic loosening by alternating activation of macrophages.
Sun, Zhengfang; Kang, Jianning; Yang, Shuye; Zhang, Ying; Huang, Nana; Zhang, Xiaodi; Du, Gangqiang; Jiang, Jianhao; Ning, Bin.
Afiliación
  • Sun Z; Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
  • Kang J; Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
  • Yang S; Department of Traumatic Orthopedics, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, Shandong Province, China.
  • Zhang Y; Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
  • Huang N; Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
  • Zhang X; School of Clinical Medicine, Weifang Medical University, Weifang, Shandong Province, China.
  • Du G; Department of Traumatic Orthopedics, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, Shandong Province, China.
  • Jiang J; Department of Spinal Surgery, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China; Department of Traumatic Orthopedics, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, Shandong Province, China. Electronic address: jianha
  • Ning B; Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China; Department of Spinal Surgery, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Pro
Int Immunopharmacol ; 122: 110561, 2023 Sep.
Article en En | MEDLINE | ID: mdl-37451018
Aseptic inflammation is a major cause of late failure in total joint arthroplasty, and the primary factor contributing to the development and perpetuation of aseptic inflammation is classical macrophage activation (M1 phenotype polarization) induced by wear particles. CD73 (ecto-5'-nucleotidase) is an immunosuppressive factor that establishes an adenosine-induced anti-inflammatory environment. Although CD73 has been shown to suppress inflammation by promoting alternate macrophage activation (M2 phenotype polarization), its role in wear particle-induced aseptic inflammation is currently unknown. Our experiments were based on metabolomic assay results in a mouse model of aseptic loosening, and studied the function of CD73 in vivo and in vitro using a mouse aseptic loosening model and a mouse bone marrow derived macrophage (BMDM) inflammation model. Results show that aseptic loosening (AL) reduces the purine metabolic pathway and decreases the native expression of the metabolite adenosine. In vivo, CD73 expression was low in the bone tissue surrounding the titanium nail and synovial-like interface tissue, while in vitro experiments demonstrated that CD73 knockdown promoted titanium particles-induced aseptic inflammation. CD73 overexpression mitigated the titanium particle-mediated enhancement of LPS-induced M1 polarization while promoting the titanium particle-mediated attenuation of IL-4-induced M2 polarization. In BMDM exposed to titanium particles, CD73 promotes M2 polarization via the p38 pathway. Meanwhile, local injection of recombinant mouse CD73 protein slightly alleviated the progression of AL. Collectively, our data suggest that CD73 alleviates the process of AL, and this function is achieved by promoting alternate activation of macrophages.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteólisis / Titanio Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteólisis / Titanio Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos