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Sirtuin 6 ameliorates arthritis through modulating cyclic AMP-responsive element binding protein/CCN1/cyclooxygenase 2 pathway in osteoblasts.
Lin, Sze-Kwan; Wang, Han-Wei; Shun, Chia-Tung; Yang, Cheng-Ning; Hong, Chi-Yuan; Lai, Eddie Hsiang-Hua; Cheng, Shih-Jung; Chen, Mu-Hsiung; Yang, Hsiang; Lin, Hung-Ying; Wu, Fang-Yu; Kok, Sang-Heng.
Afiliación
  • Lin SK; Department of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan.
  • Wang HW; Department of Dentistry, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • Shun CT; Department of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan.
  • Yang CN; Graduate Institute of Clinical Dentistry, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • Hong CY; Department of Forensic Medicine and Pathology, National Taiwan University Hospital, Taipei, Taiwan.
  • Lai EH; Department of Dentistry, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • Cheng SJ; Department of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan.
  • Chen MH; Department of Dentistry, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • Yang H; College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan.
  • Lin HY; Department of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan.
  • Wu FY; Department of Dentistry, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • Kok SH; Department of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan.
J Bone Miner Metab ; 41(6): 772-784, 2023 Nov.
Article en En | MEDLINE | ID: mdl-37898986
INTRODUCTION: CCN1 is an immediate-early gene product pivotal for arthritis progression. We have previously shown that sirtuin 6 (SIRT6) inhibited hypoxia-induced CCN1 expression in osteoblasts. Herein we examined the contribution of cyclic AMP-responsive element binding protein (CREB)/CRE to this suppressive action and the influence of CCN1 on cyclooxygenase (COX) 2 synthesis. MATERIALS AND METHODS: MC3T3-E1 murine osteoblasts were cultured under normoxia (21% oxygen) or hypoxia (2% oxygen). Expressions of CCN1, phospho-CREB (Ser133), COX2 and relevant kinases were assessed by Western blot. SIRT6 was overexpressed in cultured osteoblasts and arthritic joints by a lentiviral-based technique. Activities of CCN1 gene promoter constructs were examined by luciferase reporter assay. Interaction between CREB and CCN1 promoter was assessed by chromatin immunoprecipitation (ChIP). Collagen-induced arthritis (CIA) was established in 20 rats to evaluate the effects of SIRT6 therapy on osteoblastic expressions of phospho-CREB, CCN1 and COX2. RESULTS: SIRT6 suppressed hypoxia-enhanced CCN1 expression and CREB phosphorylation. Attenuation of calcium/calmodulin-dependent protein kinase II (CaMKII) may be responsible for SIRT6-induced CREB inhibition. CRE at - 286 bp upstream of the ATG start codon was essential for CCN1 expression under hypoxia and SIRT6 reduced hypoxia-stimulated CREB/CRE interaction. Forced expression of CREB rescued SIRT6-suppressed CCN1 synthesis. CCN1 induced COX2 expression in osteoblasts. In rat CIA, the therapeutic effect of SIRT6 was accompanied by decreases in osteoblastic expressions of phospho-CREB, CCN1 and COX2. CONCLUSION: Our study indicated that the benefits of SIRT6 to inflammatory arthritis and bone resorption are at least partially derived from its modulation of CREB/CCN1/COX2 pathway in osteoblasts.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Sirtuinas Límite: Animals Idioma: En Revista: J Bone Miner Metab Asunto de la revista: METABOLISMO Año: 2023 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Japón
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Sirtuinas Límite: Animals Idioma: En Revista: J Bone Miner Metab Asunto de la revista: METABOLISMO Año: 2023 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Japón