Disruption of Jmjd3/p16Ink4a Signaling Pathway Causes Bizarre Parosteal Osteochondromatous Proliferation (BPOP)-like Lesion in Mice

Feng Zhang; Yingmei Wang; Yuying Wang; Xinli Wang; Dawei Zhang; Xiong Zhao; Runmin Jiang; Yu Gu; Guifang Yang; Xin Fu; Longyong Xu; Longxia Xu; Liting Zheng; Jing Zhang; Zengshan Li; Qingguo Yan; Jianguo Shi; Albert Roessner; Zhe Wang; Qing Li; Jing Ye; Charlie Degui Chen; Shuangping Guo; Jie Min

doi:10.1002/jbmr.4401

Disruption of Jmjd3/p16^Ink4a Signaling Pathway Causes Bizarre Parosteal Osteochondromatous Proliferation (BPOP)-like Lesion in Mice

J Bone Miner Res. 2021 Oct;36(10):1931-1941. doi: 10.1002/jbmr.4401. Epub 2021 Jul 12.

Authors

Feng Zhang^#^{1

2}, Yingmei Wang^#¹, Yuying Wang¹, Xinli Wang³, Dawei Zhang³, Xiong Zhao³, Runmin Jiang⁴, Yu Gu¹, Guifang Yang⁵, Xin Fu¹, Longyong Xu⁶, Longxia Xu⁶, Liting Zheng⁶, Jing Zhang¹, Zengshan Li¹, Qingguo Yan¹, Jianguo Shi¹, Albert Roessner⁷, Zhe Wang¹, Qing Li¹, Jing Ye¹, Charlie Degui Chen⁶, Shuangping Guo¹, Jie Min⁸

Affiliations

¹ State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
² Department of Pathology, Air Force Medical Center (Air Force General Hospital), PLA, Beijing, China.
³ Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
⁴ Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
⁵ Department of Surgery, Hospital of Xi'an Jiaotong University, Xi'an, China.
⁶ State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
⁷ Department of Pathology, Otto-von-Guericke University, Magdeberg, Germany.
⁸ Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.

^# Contributed equally.

PMID: 34173271
DOI: 10.1002/jbmr.4401

Abstract

Bizarre parosteal osteochondromatous proliferation (BPOP), or Nora's lesion, is a rare benign osteochondromatous lesion. At present, the molecular etiology of BPOP remains unclear. JMJD3(KDM6B) is an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression. Previously, Jmjd3 was shown to be critical for bone development and osteoarthritis. Here, we report that conditional deletion of Jmjd3 in chondrogenic cells unexpectedly resulted in BPOP-like lesion in mice. Biochemical investigations revealed that Jmjd3 inhibited BPOP-like lesion through p16^Ink4a . Immunohistochemistry and RT-qPCR assays indicated JMJD3 and p16^INK4A level were significantly reduced in human BPOP lesion compared with normal subjects. This was further confirmed by Jmjd3/Ink4a double-gene knockout mice experiments. Therefore, our results indicated the pathway of Jmjd3/p16^Ink4a may be essential for the development of BPOP in human. © 2021 American Society for Bone and Mineral Research (ASBMR).

Keywords: BIZARRE PAROSTEAL OSTEOCHONDROMATOUS PROLIFERATION (BPOP); JMJD3; p16Ink4a.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Neoplasms*
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p16 / genetics
Mice
Osteochondroma* / genetics
Signal Transduction

Substances

Cyclin-Dependent Kinase Inhibitor p16