Molecular crosstalk between articular cartilage, meniscus, synovium, and subchondral bone in osteoarthritis

Bone & Joint Research

article

Maochun Wang¹  Guihua Tan¹  Huiming Jiang¹  Anlong Liu¹  Rui Wu¹  Jiawei Li¹  Ziying Sun¹  Zhongyang Lv¹  Wei Sun²  Dongquan Shi¹ 

[1] State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School;Department of Orthopedics, The Affiliated Jiangyin Hospital of Southeast University Medical College

关键词: Osteoarthritis;    Crosstalk;    Transcriptome;    Differentially expressed genes;    Ligand-receptor;    articular cartilage;    subchondral bone;    Meniscus;    Osteoarthritis (OA);    chondrocytes;    extracellular matrix;    synovial fluid;    interleukins;    Gene Expression;    degenerative joint disease;   

DOI  :  10.1302/2046-3758.1112.BJR-2022-0215.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 worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA.MethodsWe used four groups of transcription profiles acquired from the Gene Expression Omnibus database, including articular cartilage, meniscus, synovium, and subchondral bone, to screen differentially expressed genes during OA. Potential crosstalk between tissues was depicted by ligand-receptor pairs.ResultsDuring OA, there were 626, 97, 1,060, and 2,330 differentially expressed genes in articular cartilage, meniscus, synovium, and subchondral bone, respectively. Gene Ontology enrichment revealed that these genes were enriched in extracellular matrix and structure organization, ossification, neutrophil degranulation, and activation at different degrees. Through ligand-receptor pairing and proteome of OA synovial fluid, we predicted ligand-receptor interactions and constructed a crosstalk atlas of the whole joint. Several interactions were reproduced by transwell experiment in chondrocytes and synovial cells, including TNC-NT5E, TNC-SDC4, FN1-ITGA5, and FN1-NT5E. After lipopolysaccharide (LPS) or interleukin (IL)-1β stimulation, the ligand expression of chondrocytes and synovial cells was upregulated, and corresponding receptors of co-culture cells were also upregulated.ConclusionEach tissue displayed a different expression pattern in transcriptome, demonstrating their specific roles in OA. We highlighted tissue molecular crosstalk through ligand-receptor pairs in OA pathophysiology, and generated a crosstalk atlas. Strategies to interfere with these candidate ligands and receptors may help to discover molecular targets for future OA therapy.

【 授权许可】

CC BY-NC