Bone morphogenetic protein 2 controls steroid-induced osteonecrosis of the femoral head via directly inhibiting interleukin-34 expression

in Journal of Molecular Endocrinology
Authors:
Meng Wang Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

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Hong Sung Min Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

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Haojie Shan Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

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Yiwei Lin Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

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Wenyang Xia Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

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Fuli Yin Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

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Chaolai Jiang Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

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Xiaowei Yu Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

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Correspondence should be addressed to X Yu: yuxw@sjtu.edu.cn

*(M Wang and H S Min contributed equally to this work)

DOI:
https://doi.org/10.1530/JME-21-0163
Volume/Issue:
Volume 68: Issue 1
Article Type:
Research Article
Page Range:
1–9
Online Publication Date:
21 Oct 2021
Copyright:
© Society for Endocrinology 2021
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Increased inflammatory response is one of the major characteristics of osteonecrosis of the femoral head (ONFH). We aimed to investigate the function of bone morphogenetic protein 2 (BMP-2)/interleukin (IL)-34 axis in the inflammatory responses of ONFH. The systemic and local expression of BMPs in ONFH patients was detected by qRT-PCR and ELISA. In vitro osteoclast differentiation and ONFH mouse models, induced by 20 mg/kg methylprednisolone through i.m. injection, were established using WT and BMP-2−/− mice to explore the regulatory role of BMP-2 in pro-inflammatory responses and bone defects of ONFH. IL-34 expression and function were examined in vitro and in vivo through qRT-PCR, tartrate-resistant acid phosphatase (TRAP) staining, and gene knockout. The systemic and local expression of BMPs was elevated in ONFH patients. BMP-2 reduced the production of pro-inflammatory cytokines and inhibited the differentiation of osteoclasts. Mechanistically, BMP-2 inhibited osteoclasts formation through suppressing IL-34 expression and then promoted bone repair and alleviated ONFH. In conclusion, our study reveals that BMP-2 inhibits inflammatory responses and osteoclast formation through downregulating IL-34.

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Online ISSN:
1479-6813
Print ISSN:
0952-5041
Copyright:
© Society for Endocrinology 2021
Page(s):
9
Article Type:
Research Article
Received Date:
15 Sep 2021
Accepted Date:
28 Sep 2021
Print Publication Date:
01 Jan 2022
Online Publication Date:
21 Oct 2021
Keywords:
ONFH; osteoclast; inflammation; BMP-2; IL-34

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