MicroRNA‐101a‐3p could be involved in the pathogenesis of temporomandibular joint osteoarthritis by mediating UBE2D1 and FZD4

Abstract

Background Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease that gradually affects the articular cartilage, synovium, and bone structure. To date, the molecular mechanism of TMJOA pathogenesis remains unclear. The aim of this study was to explore the biological function of the micro‐ribonucleic acid 101a‐3p (miR‐101a‐3p) and its role in TMJOA. Methods We detected the effect of interleukin‐1β (IL‐1β) on chondrocyte proliferation using Cell Counting Kit‐8 (CCK‐8) technology. Using quantitative polymerase chain reaction (qPCR), we detected transcription levels of miR‐101a‐3p in a rat model with TMJOA and inflamed chondrocytes, as well as in a group of normal rats. The effect of miR‐101a‐3p on apoptosis was examined in vitro using flow cytometry (FCM). We then analyzed the target of miR‐101a‐3p via bioinformatics and confirmed it using a luciferase reporter assay (LRA). Results We showed that IL‐1β could inhibit proliferation of chondrocytes. We found that miR‐101a‐3p levels were significantly lower in the rat inflammation model with TMJOA and inflamed chondrocytes than in the normal group. Additionally, miR‐101a‐3p substantially promoted apoptosis of chondrocytes, and both bioinformatic analyses and LRA found that this miRNA targeted the genes ubiquitin‐conjugating enzyme 2D1 (UBE2D1) and Frizzled class receptor 4 (FZD4). Conclusion Our results suggested that miR‐101a‐3p was involved in the pathogenesis of TMJOA and that its mechanism was probably interaction with its target genes UBE2D1 and FZD4.

Elucidating the role of ubiquitination and deubiquitination in osteoarthritis progression

“…Inactivation of PTEN alleviated EGFR ubiquitination and aggravated EGFR expression via destabilization of the EGFR-Cbl complex, contributing to suppression of extracellular matrix degradation in cartilage and promotion of autophagy in chondrocyte (168). In addition, it is necessary to describe that ubiquitin conjugating enzymes involved in osteoarthritis pathogenesis (169,170). For example, miR-101a-3p increased apoptosis of chondrocytes via targeting FZD4 and ubiquitin-conjugating enzyme 2D1 (UBE2D1), leading to involvement of pathogenesis of temporomandibular joint osteoarthritis (169).…”

Clinical Perspectives of Non-Coding RNA in Oral Inflammatory Diseases and Neuropathic Pain: A Narrative Review

“…In another study, miR-140-5p was found to regulate temporomandibular joint osteoarthritis (TMJOA) via the TGF-β/Smad signaling pathway and might serve as a novel prognostic factor of TMJ degenerative changes [ 116 ]. A very recent study showed that the levels of miR-101a-3p were significantly lower in a rat inflammation model with TMJOA and involved in apoptosis of chondrocytes [ 117 ]. Using miR21 knockout mice, Zhang et al [ 118 ], reported that miR21, via critical regulation of growth differentiation factor 5 in chondrocytes, regulates cartilage matrix degradation and contributes to the progression of TMJ-OA.…”

Action of Hyaluronic Acid as a Damage-Associated Molecular Pattern Molecule and Its Function on the Treatment of Temporomandibular Disorders

“…Other miRNAs such as miR-101a-3p (53) and miR-21-5p (54) have been correlated to the DJD. For example, one study found that the miR-101a-3p was decreased in an inflammatory model of DJD (53), and its neuropathic pain-attenuating activity was demonstrated in chronic constriction injury rat models through targeting mTOR (55). On the other hand, the upregulation of miR-21-5p was associated with cartilage matrix degradation and progression of the DJD (54).…”