Creb5 establishes the competence for Prg4 expression in articular cartilage
Name
s42003-021-01857-0.pdf
Description
Published version
Size
3.17 MB
Format
Adobe PDF
Checksum (MD5)
08c62eb24e06d526657d212cdbd93073
Author(s)
Zhang, Cheng-Hai
Gao, Yao
Jadhav, Unmesh
Hung, Han-Hwa
Holton, Kristina M
Grodzinsky, Alan J
Shivdasani, Ramesh A
Lassar, Andrew B
Date Issued
2021
Journal
Communications Biology
Publisher
Springer Science and Business Media LLC
Version
Final published version
Abstract
AbstractA hallmark of cells comprising the superficial zone of articular cartilage is their expression of lubricin, encoded by the Prg4 gene, that lubricates the joint and protects against the development of arthritis. Here, we identify Creb5 as a transcription factor that is specifically expressed in superficial zone articular chondrocytes and is required for TGF-β and EGFR signaling to induce Prg4 expression. Notably, forced expression of Creb5 in chondrocytes derived from the deep zone of the articular cartilage confers the competence for TGF-β and EGFR signals to induce Prg4 expression. Chromatin-IP and ATAC-Seq analyses have revealed that Creb5 directly binds to two Prg4 promoter-proximal regulatory elements, that display an open chromatin conformation specifically in superficial zone articular chondrocytes; and which work in combination with a more distal regulatory element to drive induction of Prg4 by TGF-β. Our results indicate that Creb5 is a critical regulator of Prg4/lubricin expression in the articular cartilage.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/S42003-021-01857-0
