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1,25-Dihydroxyvitamin D3 attenuates disease severity and induces synoviocyte apoptosis in a concentration-dependent manner in rats with adjuvant-induced arthritis by inactivating the NF-κB signaling pathway

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Abstract

An aggressive proliferation of synoviocytes is the hallmark of rheumatoid arthritis (RA). Emerging evidence shows that inhibiting the NF-κB signaling pathway with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] may be a therapeutic approach for controlling inflammatory diseases. In this study, we demonstrated the protective effects of three different 1,25(OH)2D3 concentration on adjuvant-induced arthritis (AA) rats through the NF-κB signaling pathway and their pro-apoptotic roles in cultured adjuvant-induced arthritis synoviocytes (AIASs). AA rats were prepared by injecting complete Freund’s adjuvant and independently given daily intraperitoneal injection of 1,25(OH)2D3 at concentrations of 50, 100, and 300 ng/day/kg. Subsequently, AIASs were isolated from the inflamed joints of AA rats to test the effects of 1,25(OH)2D3 on AIASs in vitro. Intraperitoneal injection of 1,25-(OH)2D3 was found to induce a concentration- and time-dependent improvement in relieving the symptoms of AA. We found an increased paw withdrawal thermal latency (PWTL) in the affected paw of AA rats as the concentration of 1,25-(OH)2D3 increased. 1,25-(OH)2D3 treatment reduced levels of inflammatory factors in synovial tissues of AA rats. In the case of cultured AIASs, 1,25-(OH)2D3 was shown to inhibit cell proliferation and induce cell apoptosis in a concentration-dependent manner. Additionally, 1,25-(OH)2D3 inhibited the activation of the NF-κB signaling pathway. In conclusion, our study provides evidence emphasizing that 1,25(OH)2D3 has the potential to attenuate disease severity in RA potentially due to its contributory role in synoviocyte proliferation and apoptosis. The protective role of 1,25(OH)2D3 against RA depends on the NF-κB signaling pathway.

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Acknowledgements

This study was supported by Key Research and Development Program of Shandong Province (no. 2016GSF201232) and the Natural Science Foundation of Shandong Province (no. ZR2017LH028). We would like to give our sincere appreciation to the reviewers for their helpful comments on this article.

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Author notes

  1. Hua-Qiang Sun and Dong Yan contributed equally to this work.

Authors and Affiliations

  1. Department of Bone and Joint Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan, 250014, Shandong, People’s Republic of China

    Hua-Qiang Sun, Dong Yan, Hong-Zheng Meng, Ye-Yong Zhang, Lu-Xu Yin, Xin-Feng Yan & Shu-Feng Li

  2. Department of Orthopedics, Weihai Hospital of Traditional Chinese Medicine, Weihai, 264200, People’s Republic of China

    Qin-Nan Wang

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  1. Hua-Qiang Sun
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Correspondence to Xin-Feng Yan or Shu-Feng Li.

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Ethical statement

The study was conducted with the approval of the Animal Ethics Committee of Shandong Provincial Qianfoshan Hospital, Shandong University. All experimental procedures were performed on laboratory animals in accordance with institutional guidelines for the care and use of laboratory animals.

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Sun, HQ., Yan, D., Wang, QN. et al. 1,25-Dihydroxyvitamin D3 attenuates disease severity and induces synoviocyte apoptosis in a concentration-dependent manner in rats with adjuvant-induced arthritis by inactivating the NF-κB signaling pathway. J Bone Miner Metab 37, 430–440 (2019). https://doi.org/10.1007/s00774-018-0944-x

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  • DOI: https://doi.org/10.1007/s00774-018-0944-x

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