Matrix stiffness aggravates osteoarthritis progression through H3K27me3 demethylation induced by mitochondrial damage

Tianyou Kan; Hanjun Li; Lingli Hou; Junqi Cui; Yao Wang; Lin Sun; Liao Wang; Mengning Yan; Zhifeng Yu

iScience (Aug 2024)

Matrix stiffness aggravates osteoarthritis progression through H3K27me3 demethylation induced by mitochondrial damage

Tianyou Kan,
Hanjun Li,
Lingli Hou,
Junqi Cui,
Yao Wang,
Lin Sun,
Liao Wang,
Mengning Yan,
Zhifeng Yu

Affiliations

Tianyou Kan: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China
Hanjun Li: Renji-Med X Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Lingli Hou: Shanghai Institute of Precision Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Junqi Cui: Department of Pathology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Yao Wang: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Lin Sun: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Liao Wang: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Mengning Yan: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; Corresponding author
Zhifeng Yu: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; Corresponding author

Journal volume & issue: Vol. 27, no. 8
p. 110507

Abstract

Read online

Summary: Abnormal epigenetics is the initial factor of the occurrence and development of osteoarthritis (OA), and abnormal mechanical load is a key pathogenic factor of OA. However, how abnormal mechanical load affects chondrocyte epigenetics is unclear. Chondrocytes reportedly respond to mechanics through the extracellular matrix (ECM), which has a role in regulating epigenetics in various diseases, and mitochondria are potential mediators of communication between mechanics and epigenetics. Therefore, it is hypothesized that the matrix mechanics of cartilage regulates their epigenetics through mitochondria and leads to OA. The matrix stiffness of OA cartilage on the stress-concentrated side increases, mitochondrial damage of chondrocyte is severe, and the chondrocyte H3K27me3 is demethylated. Moreover, mitochondrial permeability transition pore (mPTP) opens to increase the translocation of plant homeodomain finger protein 8 (Phf8) into the nucleus to catalyze H3K27me3 demethylation. This provides a new perspective for us to understand the mechanism of OA based on mechanobiology.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

About the journal

Abstract

Keywords