RNA-Seq Reveals the mRNAs, miRNAs, and lncRNAs Expression Profile of Knee Joint Synovial Tissue in Osteoarthritis Patients

Abstract

Osteoarthritis (OA) is a chronic disease common in the elderly population and imposes significant health and economic burden. Total joint replacement is the only currently available treatment but does not prevent cartilage degeneration. The molecular mechanism of OA, especially the role of inflammation in disease progression, is incompletely understood. We collected knee joint synovial tissue samples of eight OA patients and two patients with popliteal cysts (controls), measured the expression levels of lncRNAs, miRNAs, and mRNAs in these tissues by RNA-seq, and identified differentially expressed genes (DEGs) and key pathways. In the OA group, 343 mRNAs, 270 lncRNAs, and 247 miRNAs were significantly upregulated, and 232 mRNAs, 109 lncRNAs, and 157 miRNAs were significantly downregulated. mRNAs potentially targeted by lncRNAs were predicted. Nineteen overlapped miRNAs were screened based on our sample data and GSE 143514 data. Pathway enrichment and functional annotation analyses showed that the inflammation-related transcripts CHST11, ALDH1A2, TREM1, IL-1β, IL-8, CCL5, LIF, miR-146a-5p, miR-335-5p, lncRNA GAS5, LINC02288, and LOC101928134 were differentially expressed. In this study, inflammation-related DEGs and non-coding RNAs were identified in synovial samples, suggesting that competing endogenous RNAs have a role in OA. TREM1, LIF, miR146-5a, and GAS5 were identified to be OA-related genes and potential regulatory pathways. This research helps elucidate the pathogenesis of OA and identify novel therapeutic targets for this disorder.

Saikosaponin D alleviates inflammatory response of osteoarthritis and mediates autophagy via elevating microRNA-199-3p to target transcription Factor-4

“…Several studies have demonstrated the role of non-coding RNA in musculoskeletal diseases [ 37 – 39 ]. Multiple studies have elucidated that miRNAs are aberrant in OA tissues [ 40 , 41 ]. The mechanism of action of SSD on OA was further discussed, and it was found that miR-199-3p was abnormal in OA and affected by SSD.…”

MicroRNA Signatures in Cartilage Ageing and Osteoarthritis

“…Chondrocyte-specific deletion of DICER in the growth plate of mice reduced the number of proliferating chondrocytes, increased hypertrophic chondrocytes and led to severe skeletal defects and premature death [ 15 ]. Several miRNAs have been associated with cartilage development and homeostasis and dysregulation of these is linked with ageing and OA [ 16 , 17 , 18 , 19 ]. miR-140 is one of the most important miRNAs in cartilage.…”

“…Inflammatory cytokines, such as interleukin 1 beta (IL-1β), exert catabolic effects in cartilage and promote degradation. Synovial tissues from OA patients are characterised by distinctive changes in the expression of several miRNAs, including miR-146a and miR-335, and these changes suggest a role of miRNAs in OA inflammation [ 18 ]. Moreover, a recent study by Zhang et al (2023) demonstrated aberrant miRNA expression in senescent chondrocytes with 279 miRNAs differentially expressed between senescent and non-senescent chondrocytes [ 26 ].…”

Exploring Talarozole as a Novel Therapeutic Approach for Osteoarthritis: Insights From Experimental Studies

“…1 Osteoarthritis typically affects the hands, hips, and knees, and forecasts show that the incidence of knee OA will raise globally, affecting an estimated 250 million people. 2 , 3 According to the Centers for Disease Control and Prevention (CDC), approximately 32 million people in the United States with OA, with the hands being among the most commonly affected body parts. Despite not being weight-bearing joints, hand OA affects about 27% of the population and can affect up to 80% of older persons.…”