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TDP-43 ameliorates aging-related cartilage degradation through preventing chondrocyte senescence.
Wang, Limeiting; Zhang, Jun; Liang, Lu; Song, Zijun; Wang, Pinwen; Ma, Liya; Liao, Zhenhui; Li, Ning; Yang, Hefeng; Li, Song.
Afiliación
  • Wang L; Yunnan Key Laboratory of Stomatology, Kunming, Yunnan, China; Department of Prosthodontics Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, Yunnan, China.
  • Zhang J; Yunnan Key Laboratory of Stomatology, Kunming, Yunnan, China; Department of Pediatric Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, Yunnan, China.
  • Liang L; Yunnan Key Laboratory of Stomatology, Kunming, Yunnan, China; Department of Prosthodontics Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, Yunnan, China.
  • Song Z; Yunnan Key Laboratory of Stomatology, Kunming, Yunnan, China; Department of Prosthodontics Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, Yunnan, China.
  • Wang P; Yunnan Key Laboratory of Stomatology, Kunming, Yunnan, China; Department of Prosthodontics Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, Yunnan, China.
  • Ma L; Yunnan Key Laboratory of Stomatology, Kunming, Yunnan, China; Department of Orthodontics Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, Yunnan, China.
  • Liao Z; Yunnan Key Laboratory of Stomatology, Kunming, Yunnan, China; Department of Prosthodontics Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, Yunnan, China.
  • Li N; Kunming Medical University School and Hospital of Stomatology, Kunming, Yunnan, China.
  • Yang H; Yunnan Key Laboratory of Stomatology, Kunming, Yunnan, China; Department of Prosthodontics Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, Yunnan, China.
  • Li S; Yunnan Key Laboratory of Stomatology, Kunming, Yunnan, China; Department of Orthodontics Dentistry, Kunming Medical University School and Hospital of Stomatology, Kunming, Yunnan, China.
Exp Gerontol ; 195: 112546, 2024 Oct 01.
Article en En | MEDLINE | ID: mdl-39153533
ABSTRACT
Senescent chondrocytes or signaling mechanisms leading to senescence are promising new therapeutic approaches for ameliorating cartilage degradation. Herein, we show that the transactive response DNA/RNA-binding protein (TDP-43) regulates chondrocyte senescence and ameliorates cartilage degradation. First, a significant decrease in TDP-43 was observed in 16-month-old mice compared with younger mice. Immunohistochemistry (IHC) analysis of mouse articular cartilage showed that p21, p16, p53, and matrix metalloprotein-13 (MMP13) were increased, but laminB1 and Collagen type II alpha1 1 chain (Col2a1) were decreased in 16-month-old mice. Furthermore, TDP-43 levels were decreased in vivo following D-galactose (D-gal) induction. Therefore, we investigated the role of TDP-43 in the senescent chondrocytes. ATDC5 cells were induced to overexpress TDP-43. Western blot analysis showed increased expression of laminB1, Ki67, and PCNA but decreased expression of p21, p16, p53, and MMP13. Senescence-associated-ß-galactosidase (SA-ß-Gal) assay, γH2AX staining, and EdU were performed to assess changes in chondrocytes, showing weaker SA-ß-Gal and γH2AX staining but stronger EdU and Alican Blue staining. However, TDP-43 deficiency had opposing effects, and similar to D-gal stimulation results. Taken together, our data verified that TDP-43 negatively correlated with senescence markers, positively correlated with cell proliferation markers, and could alleviate cartilage degradation induced by D-gal. This may be an essential mechanism of cellular senescence and cartilage degradation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Cartílago Articular / Senescencia Celular / Condrocitos / Proteínas de Unión al ADN Límite: Animals Idioma: En Revista: Exp Gerontol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Cartílago Articular / Senescencia Celular / Condrocitos / Proteínas de Unión al ADN Límite: Animals Idioma: En Revista: Exp Gerontol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido