Open AccessAugmented ERAD (ER-associated degradation) activity in chondrocytes is necessary for cartilage development and maintenance
Author(s) -
Hyo Jung Sim,
Chanmi Cho,
Ha Eun Kim,
Ju Yeon Hong,
Eun Kyung Song,
Keun Yeong Kwon,
Dong Gil Jang,
Seok Jung Kim,
HyunShik Lee,
Changwook Lee,
Taejoon Kwon,
Siyoung Yang,
Tae Joo Park
Publication year - 2022
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abl4222
Subject(s) - endoplasmic reticulum associated protein degradation , microbiology and biotechnology , cartilage , chondrogenesis , endoplasmic reticulum , extracellular matrix , chemistry , biology , unfolded protein response , anatomy
Chondrocytes secrete massive extracellular matrix (ECM) molecules that are produced, folded, and modified in the endoplasmic reticulum (ER). Thus, the ER-associated degradation (ERAD) complex—which removes misfolded and unfolded proteins to maintain proteostasis in the ER— plays an indispensable role in building and maintaining cartilage. Here, we examined the necessity of the ERAD complex in chondrocytes for cartilage formation and maintenance. We show that ERAD gene expression is exponentially increased during chondrogenesis, and disruption of ERAD function causes severe chondrodysplasia in developing embryos and loss of adult articular cartilage. ERAD complex malfunction also causes abnormal accumulation of cartilage ECM molecules and subsequent chondrodysplasia. ERAD gene expression is decreased in damaged cartilage from patients with osteoarthritis (OA), and disruption of ERAD function in articular cartilage leads to cartilage destruction in a mouse OA model.