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: Tags: Original Article Source Type: research