MicroRNA-410-3p modulates chondrocyte apoptosis and inflammation by targeting high mobility group box 1 (HMGB1) in an osteoarthritis mouse model

Abstract

Background: Osteoarthritis (OA) is the most prevalent type of arthritis, which commonly involves inflammation in the articular cartilage in OA pathogenesis. MicroRNAs (miRNAs) play essential roles in the regulation and pathophysiology of various diseases including OA. MiR-410-3p has been demonstrated to mediate inflammatory pathways, however, the regulatory functions of miR-410-3p in OA remain largely unknown. Methods: The regulations of miR-410-3p were investigated in OA. Mouse primary chondrocytes and mouse in vivo models were used. The expression levels of miR-410-3p and HMGB1 were measured by qPCR. The transcription activity of NF-κB was assessed by luciferase reporter assay. MTT assay was performed to assess cellular proliferation. Cell apoptosis was evaluated with the Fluorescein Isothiocyanate (FITC) Annexin V assay. Expression levels of proteins were determined by Western blot. Results: The results demonstrated that miR-410-3p was markedly downregulated in articular cartilage tissues as well as in lipopolysaccharide (LPS)-treated chondrocytes in OA mice. In addition, upregulation of miR-410-3p markedly inhibited LPS-induced apoptosis of chondrocytes. The results also demonstrated that the high mobility group box 1 (HMGB1) was a target of miR-410-3p. LPS-induced upregulated expression of HMGB1 significantly suppressed expression of miR-410-3p. Furthermore, upregulation of miR-410-3p markedly inhibited HMGB1 expression, the nuclear factor (NF)-kB activity and pro-inflammatory cytokines production. Taken together, the results suggested that miR-410-3p targeted HMGB1 and modulated chondrocytes apoptosis and inflammation through the NF-κB signaling pathway. Conclusions: These findings provide insights into the potential of miR-410-3p/ HMGB1 as therapeutic targets for OA treatment.

Unraveling the Signaling Secretome of Platelet-Rich Plasma: Towards a Better Understanding of Its Therapeutic Potential in Knee Osteoarthritis

“…HMGB1 is an alarmin present in the extracellular environment after chondrocyte or macrophage pyroptosis (death). Actually, this protein is a target in the development of miRNA therapies for OA [50], as early protein blockade can decrease cartilage deterioration [51]. Current predictions revealed that PRP influences HMGB1 signaling.…”

Enhanced Expression of Serum miR-410-3p Reflects The Disease Progression in Anti-gp210 Positive Primary Biliary Cholangitis

“…Hierarchical clustering of the 60 identi ed miRNA pro les highlighted that the patterns characterizing the patients with anti-gp210 positive PBC differed from those characterizing the patients with anti-gp210 negative PBC, suggesting that some miRNAs may be involved in the production of anti-gp210 antibodies, and even the clinical progression of PBC, or that some cases may progress as a result of speci c changes in the expression of some miRNAs. We suspected that these miRNAs might play important roles in the disease process, and we focused on one potentially important miRNA, miR-410-3p, which had previously been reported in autoimmune diseases including rheumatoid arthritis, osteoarthritis and various cancers [10,23,24]. We found that expression of miR-410-3p changed signi cantly: real-time PCR con rmed that miR-410-3p in serum from patients with anti-gp210 antibodies positive PBC showed higher expression in comparison with the patients with anti-gp210 antibodies negative PBC and healthy controls.…”

“…These data indicate that dysregulation of miR-410-3p occurs in a tissue-speci c manner in different types of diseases. One study reported that miR-410-3p can protect chondrocytes from apoptosis by regulating NF-kB signaling pathway via targeting HMGB1 in osteoarthritis [10]. Additionally, previous studies have shown that miR-410-3p suppresses cytokine release from broblast-like synoviocytes by regulating NF-kB signaling in rheumatoid arthritis [24].…”

“…MicroRNAs (miRNAs) are a group of endogenous non-coding small RNA molecules of 21-23 nucleotides in length which bind imperfectly to the complementary sequences in the 3' untranslated region (UTR) of target messenger RNAs and repress their transcription and translation [10]. MiRNAs are involved in several important biological processes including cell division, differentiation, proliferation, apoptosis, carcinogenesis, and immune function, and so on [11].…”

The Role of microRNAs in Pulp Inflammation

“…In another study in mice with osteoarthritis (OA), miR-410 was observed to be markedly downregulated in articular cartilage tissues, as well as in LPS-treated chondrocytes, in OA mice. While the upregulation of miR-410 markedly inhibited the expression of high mobility group box protein (HMGB)-1, a target gene of miR-410, as well as the activity of NF-κB and the production of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α [176]. On the other hand, Wang et al reported that miR-410 expression levels were downregulated in synovial tissues and fibroblast-like synoviocytes (FLSs).…”