Int J Biol Sci 2021; 17(5):1353-1360. doi:10.7150/ijbs.57962

Research Paper

IKKe in osteoclast inhibits the progression of methylprednisolone-induced osteonecrosis

Yingjie Liu1*, Haojie Shan1*, Yang Zong1, Yiwei Lin1, Wenyang Xia1, Nan Wang2, Lihui Zhou3, Youshui Gao1, Xin Ma1, Chaolai Jiang1, Xiaowei Yu1✉

1. Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
2. Department of Emergency, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
3. Department of Orthopaedic Surgery, Xiangshan First People's Hospital, Ningbo 315700, Zhejiang, China.
* These authors contributed equally to this work.

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Citation:
Liu Y, Shan H, Zong Y, Lin Y, Xia W, Wang N, Zhou L, Gao Y, Ma X, Jiang C, Yu X. IKKe in osteoclast inhibits the progression of methylprednisolone-induced osteonecrosis. Int J Biol Sci 2021; 17(5):1353-1360. doi:10.7150/ijbs.57962. Available from https://www.ijbs.com/v17p1353.htm

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Abstract

Previous studies have described that NF-κB signaling mediated by NFκB-inducing kinase (NIK) plays a critical role of the differentiation of osteoclasts. We aim to explore the role of IKKe in methylprednisolone -induced osteonecrosis of the femoral head (ONFH). Methylprednisolone-induced ONFH mice model was successfully established, and subjected to micro computed tomography to detect the femoral head image of the mice. Bone marrow cells from experimental mice were collected and cultured. qPCR and immunoblot were performed to examine the possible signal pathways of IKKe involvement, and osteoclast-related gene expressions in IKKe+/+ and IKKe-/- cells in vitro and in vivo were examined. It was found that the levels of IKKe decreased in ONFH patients, and IKKe interacted with NIK in the NF-κB signal pathway to suppress osteoclasts via inhibiting the transcription of NIK. Furthermore, IKKe knockout promoted the osteoclastogenesis in mice model. Finally, IKKe knockout suppressed methylprednisolone-induced ONFH and pro-inflammatory responses in mice model. Our findings show a mechanism of IKKe inhibition of the progression of methylprednisolone-induced ONFH via the NIK/NF-κB pathway.

Keywords: ONFH, IKKe, non-canonical NF-κB pathway, osteoclasts.