Disruption of Jmjd3/p16Ink4a signaling pathway causes bizarre parosteal osteochondromatous proliferation (BPOP) ‐like lesion in mice
ABSTRACTBizarre parosteal osteochondromatous proliferation (BPOP), or Nora's lesion, is a rare benign osteochondromatous lesion. To the present, the molecular aetiology of BPOP remains unclear. JMJD3(KDM6B) is an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression. Previously, Jmjd3 was showed to be critical for bone development and osteoarthritis. Here, we reported that conditional deletion of Jmjd3 in chondrogenic cells unexpectively resulted in BPOP-like lesion in mice. Biochemical investigations revealed that Jmjd3 inhibited BPOP-like lesion through p16Ink4a. Immunohistochemistry and RT-qPCR assays indicated JMJD3 and p16INK4A level were significantly reduced in human BPOP lesion compared to normal subjects. This was further confirmed byJmjd3/Ink4a double genes knockout mice experiments. Therefore, our results indicated the pathway of Jmjd3/p16Ink4a may be essential for the development of BPOP in human.
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: 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,
Tags: Original Article Source Type: research