IKKe in osteoclast inhibits the progression of methylprednisolone-induced osteonecrosis
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Updated: Nov 8, 2025
A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders
Published on: June 8, 2014
Yingjie Liu1, Haojie Shan1, Yang Zong1
1Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
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.
Insights
The study reveals that Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon (IKKe) suppresses osteoclast formation in osteonecrosis of the femoral head (ONFH). IKKe deficiency exacerbates ONFH, highlighting its protective role.
Area of Science:
- Molecular Biology
- Immunology
- Orthopedics
Background:
- NF-κB signaling, particularly via NFκB-inducing kinase (NIK), is crucial for osteoclast differentiation.
- Osteonecrosis of the femoral head (ONFH) involves abnormal osteoclast activity.
Purpose of the Study:
- To investigate the role of Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon (IKKe) in methylprednisolone-induced ONFH.
- To elucidate the underlying molecular mechanisms involving the NIK/NF-κB pathway.
Main Methods:
- Established a methylprednisolone-induced ONFH mouse model.
- Utilized micro-computed tomography for imaging.
- Performed qPCR and immunoblotting on bone marrow cells (IKKe+/+ and IKKe-/-) in vitro and in vivo.
- Examined osteoclast-related gene expression.
Main Results:
- IKKe levels were decreased in ONFH patients.
- IKKe suppressed osteoclastogenesis by inhibiting NIK transcription within the NF-κB pathway.
- IKKe knockout exacerbated ONFH and pro-inflammatory responses in the mouse model.
- IKKe deficiency promoted osteoclastogenesis.
Conclusions:
- IKKe acts as a negative regulator of osteoclastogenesis in the context of ONFH.
- IKKe protects against methylprednisolone-induced ONFH progression via the NIK/NF-κB pathway.
- Targeting IKKe may offer a therapeutic strategy for ONFH.
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