陆军军医大学学报 (Aug 2023)

1, 25-dihydroxy vitamin D3 alleviates collagen-induced arthritis via regulating Th17/Treg ratio and RANKL/OPG axis

  • QI Kun,
  • LIU Yun,
  • TANG Tao,
  • LUO Xiwen

DOI
https://doi.org/10.16016/j.2097-0927.202302122
Journal volume & issue
Vol. 45, no. 15
pp. 1656 – 1665

Abstract

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Objective To investigate the mechanisms of 1, 25(OH)2D3 on joint inflammation and bone destruction in a mouse model of collagen-induced arthritis (CIA). Methods Thirty DBA/1J mice were equally allocated into control, CIA and intervention (VD) groups. The CIA model was established in the mice in the CIA group and VD group, meanwhile the VD group was treated with 1, 25(OH)2D3. The thickness of the hindfoot paws was measured with vernier caliper. Micro-CT scanning was used to measure bone mineral density (BMD) of the hindfoot paw, ELISA was employed to detect the serum levels of 1, 25(OH)2D3 and proinflammatory cytokines (IL-1β, IL-6, TNF-α), and flow cytometry was performed to calculate the ratio of Th17 to Treg cells in the spleen. The pathological changes of the knee joint were observed with HE staining. Western blotting was applied to detect the expression levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), NF-κB, and vitamin D receptor (VDR) in mouse ankle joints. Results 1, 25(OH)2D3 did not reduce the incidence of CIA in the of mice in the VD group, but significantly reduced joint inflammation. Obviously decreased thickness of the hindfoot paw, arthritis score, and knee histological synovitis score (HSS) were observed in the VD group than the CIA group (all P < 0.05). The CIA group presented more serious bone destruction and lower BMD and bone volume fraction (BV/TV) when compared with the VD group (both P < 0.05). The serum levels of IL-1β, IL-6 and TNF-α and ratio of Th17/Treg cells in the VD group were statistically lower than those in the CIA group (all P < 0.05). Compared with the CIA group, the VD group had notably higher protein levels of VDR and OPG, lower levels of NF-κB and RANKL, and reduced RANKL/OPG ratio in the ankle joint (all P < 0.05). Conclusion 1, 25(OH)2D3 may alleviate arthritic inflammation and suppress bone destruction in the mouse CIA model via regulating the Th17/Treg ratio and the RANKL/OPG axis.

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