Abstract

The phenotypic change of chondrocytes and the interplay between cartilage and subchondral bone in osteoarthritis (OA) has received much attention. Structural changes with nerve ingrowth and vascular penetration within OA cartilage may contribute to arthritic joint pain. The aim of this study was to identify differentially expressed genes and potential miRNA regulations in OA knee chondrocytes through next-generation sequencing and bioinformatics analysis. Results suggested the involvement of SMAD family member 3 (SMAD3) and Wnt family member 5A (WNT5A) in the growth of blood vessels and cell aggregation, representing features of cartilage damage in OA. Additionally, 26 dysregulated genes with potential miRNA–mRNA interactions were identified in OA knee chondrocytes. Myristoylated alanine rich protein kinase C substrate (MARCKS), epiregulin (EREG), leucine rich repeat containing 15 (LRRC15), and phosphodiesterase 3A (PDE3A) expression patterns were similar among related OA cartilage, subchondral bone and synovial tissue arrays in Gene Expression Omnibus database. The Ingenuity Pathway Analysis identified MARCKS to be associated with the outgrowth of neurite, and novel miRNA regulations were proposed to play critical roles in the pathogenesis of the altered OA knee joint microenvironment. The current findings suggest new perspectives in studying novel genes potentially contributing to arthritic joint pain in knee OA, which may assist in finding new targets for OA treatment.

Highlights

  • Osteoarthritis (OA) is one of the common musculoskeletal disorders with increased incidence in the elderly [1]

  • The results showed that the expression patterns of ACVRL1, ALPL, GDF6, TMEM119, Wnt family member 5A (WNT5A), CYTL1, and SOX9 in OA knee cartilages were conJ.sCislitne.nMt ewd.i2t0h18o,u7r, xeFxOpRrePsEsEioRnRpErVoIEfiWle of OA chondrocytes (Figure 2A,B), while the expression patter7nosf 23 of ACVRL1, ALPL, BMP4, GDF6, SMAD family member 3 (SMAD3), TMEM119, and WNT5A in subchondral bones of OA knees weerexpcroensssiisotnenptawttietrhnosuorf AdaCtVaR(FLi1g,uArLeP3LA,BBM)

  • Our current study identified the up-regulated WNT5A in OA knee chondrocytes, and bioinformatics analysis suggested the involvement of WNT5A in the positive regulation of cartilage development and the aggregation of cells, suggesting the important role of WNT5A in cartilage degradation in knee OA

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Summary

Introduction

Osteoarthritis (OA) is one of the common musculoskeletal disorders with increased incidence in the elderly [1]. The cardinal pathological change in the OA joint is the destruction of articular cartilage. The biological functions of chondrocytes and histopathological changes of articular cartilage in OA have been extensively studied [5,7]. While cartilage breakdown is the major consequence of OA, there is a growing consensus that OA is considered a disease of the entire joint, affecting all tissues in the joint, including cartilage, subchondral bone, meniscus, ligament, and synovium, and is not merely a process of wear and tear [8]. The interplay between cartilage and subchondral bone, mainly mediated by chondrocytes and osteoblasts within the two compartments, has received much attention and potentially contributes to the pathogenesis of OA [4]. The abnormal remodeling and increased vascularization observed in the OA joint facilitate molecular transport and cellular interaction between cartilage and bone [9]

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