1, 25-dihydroxy-vitamin D3 with tumor necrosis factor-alpha protects against rheumatoid arthritis by promoting p53 acetylation-mediated apoptosis via Sirt1 in synoviocytes

• DOI: 10.1038/cddis.2016.300
• Publication Date: 2016-10-20T12:52:47Z
• Authors: Xin Gu; Bingjie Gu; Xianhui Lv; Zhenzhen Yu; Rong Wang; Xiaoli Zhou; Wanxin Qiao; Zhiyuan Mao; Guoping Zuo; Qing Li; Dengshun Miao; Jianliang Jin
• Keywords: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Cell Nucleus; Inflammation; Mice, Inbred BALB C; 0303 health sciences; Synovial Membrane; Acetylation; Apoptosis; Fibroblasts; Protective Agents; Arthritis, Experimental; Synoviocytes; Bone and Bones; 3. Good health; Arthritis, Rheumatoid; Protein Transport; 03 medical and health sciences; Cartilage; Sirtuin 1; Animals; Humans; Original Article; Cell Proliferation; Signal Transduction

Impaired apoptosis of fibroblast-like synoviocytes (FLSs) causes synovial hyperplasia, facilitating destruction cartilage and bone in rheumatoid arthritis (RA). Tumor necrosis factor (TNF)-α, a dominant inflammatory mediator RA pathogenesis, promotes progression symptoms. Prevalence 1, 25-dihydroxy-vitamin D3 (hereafter termed VD) deficiency is 30-63% patients with RA. Whether VD leads to or enhances TNF-α-mediated FLSs ameliorate unclear. To determine this, 10-week-old CYP27B1-deficient (CYP27B1-/-) mice collagen-induced (CIA) were intraperitoneally treated 1 μg/kg every other day for 9 weeks. phenotypes compared between vehicle-treated CYP27B1-/- wild-type CIA mice. Human FLS-MH7A cells Dulbecco's modified Eagle's medium (DMEM) without fetal bovine serum (FBS) 24 h, then different concentrations TNF-α, human vitamin D receptor (VDR) siRNA the p53 pro-apoptotic inhibitor pifithrin-α. Apoptosis signaling analyzed. The 19-week-old had increased cumulative scores levels serous factors C-reactive protein. They exacerbated articular destruction, joint space narrowing, stiffness, deformity dysfunction, synovitis TNF-α secretion, FLS hyperplasia proliferation decreased These that aggravated by CYP27B1 largely rescued treatment. In vitro, treatment upregulated acetylation-mediated MH7A promoting Sirt1 translocation from nucleus cytoplasm. findings indicated protected against FLSs. results clinical administration could be specific therapy promote prevent progression.