Identification of mechanics-responsive osteocyte signature in osteoarthritis subchondral bone

Bone & Joint Research

article

Jun Zhou¹  Zhiyi He²  Jiarui Cui³  Xiaoling Liao⁴  Hui Cao⁵  Yo Shibata¹  Takashi Miyazaki¹  Jiaming Zhang² 

[1] Department of Conservative Dentistry, Division of Biomaterials and Engineering, Showa University School of Dentistry;Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;School of Rehabilitation and Health Preservation, Chengdu University of Traditional Chinese Medicine;Department of Prosthodontics, Tianjin Stomatological Hospital, Hospital of Stomatology, Nankai University;Department of Orthopedics, Renmin Hospital of Wuhan University

关键词: Osteoarthritis;    Subchondral bone;    Mechanics;    Osteocyte;    Transcriptome;    Osteocytes;    Osteoarthritis (OA);    bone remodelling;    transforming growth factor beta;    tibial plateaus;    lesioned;    lateral tibial plateaus;    extracellular matrix;    RNA;   

DOI  :  10.1302/2046-3758.116.BJR-2021-0436.R1

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

AimsOsteoarthritis (OA) is a common degenerative joint disease. The osteocyte transcriptome is highly relevant to osteocyte biology. This study aimed to explore the osteocyte transcriptome in subchondral bone affected by OA.MethodsGene expression profiles of OA subchondral bone were used to identify disease-relevant genes and signalling pathways. RNA-sequencing data of a bone loading model were used to identify the loading-responsive gene set. Weighted gene co-expression network analysis (WGCNA) was employed to develop the osteocyte mechanics-responsive gene signature.ResultsA group of 77 persistent genes that are highly relevant to extracellular matrix (ECM) biology and bone remodelling signalling were identified in OA subchondral lesions. A loading responsive gene set, including 446 principal genes, was highly enriched in OA medial tibial plateaus compared to lateral tibial plateaus. Of this gene set, a total of 223 genes were identified as the main contributors that were strongly associated with osteocyte functions and signalling pathways, such as ECM modelling, axon guidance, Hippo, Wnt, and transforming growth factor beta (TGF-β) signalling pathways. We limited the loading-responsive genes obtained via the osteocyte transcriptome signature to identify a subgroup of genes that are highly relevant to osteocytes, as the mechanics-responsive osteocyte signature in OA. Based on WGCNA, we found that this signature was highly co-expressed and identified three clusters, including early, late, and persistently responsive genes.ConclusionIn this study, we identified the mechanics-responsive osteocyte signature in OA-lesioned subchondral bone.

【 授权许可】

CC BY-NC