Abstract
BackgroundMiR-24-3p has been reported to be involved in an osteoarthritis (OA)-resembling environment. However, the functional role and underlying mechanism of miR-24-3p in chondrocyte injury associated with OA remains unknown.MethodsThe expression of miR-24-3p was determined using reverse transcription quantitative PCR analysis in OA cases and control patients, as well as IL-1β-stimulated chondrocyte cell line CHON-001. The cell viability was analyzed by CCK-8 assay. Apoptosis status was assessed by caspase-3 activity detection. The pro-inflammatory cytokines (TNF-α and IL-18) were determined using ELISA assay. The association between miR-24-3p and B cell leukemia 2-like 12 (BCL2L12) was confirmed by luciferase reporter assay.ResultsWe first observed that miR-24-3p expression level was lower in the OA cases than in the control patients and IL-1β decreased the expression of miR-24-3p in the chondrocyte CHON-001. Functionally, overexpression of miR-24-3p significantly attenuated IL-1β-induced chondrocyte injury, as reflected by increased cell viability, decreased caspase-3 activity, and pro-inflammatory cytokines (TNF-α and IL-18). Western blot analysis showed that overexpression of miR-24-3p weakened IL-1β-induced cartilage degradation, as reflected by reduction of MMP13 (Matrix Metalloproteinase-13) and ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs-5) protein expression, as well as markedly elevation of COL2A1 (collagen type II). Importantly, BCL2L12 was demonstrated to be a target of miR-24-3p. BCL2L12 knockdown imitated, while overexpression significantly abrogated the protective effects of miR-24-3p against IL-1β-induced chondrocyte injury.ConclusionsIn conclusion, our work provides important insight into targeting miR-24-3p/BCL2L12 axis in OA therapy.
Highlights
Osteoarthritis (OA) as a highly prevalent degenerative joint disease causes severe pain, joints stiffness, and even disability in older and middle people worldwide [1], whose primary characteristics include articular cartilage degradation caused by the imbalance of extracellular matrix (ECM) components, joint inflammation, and subchondral bone sclerosis [2, 3]
Expression level of miR-24-3p was downregulated in OA cartilage tissues and IL-1β-induced chondrocytes
MiR-24-3p expression was distinctly decreased in IL-1β-stimulated chondrocytes compared with that in untreated control group (Fig. 1b)
Summary
Osteoarthritis (OA) as a highly prevalent degenerative joint disease causes severe pain, joints stiffness, and even disability in older and middle people worldwide [1], whose primary characteristics include articular cartilage degradation caused by the imbalance of extracellular matrix (ECM) components, joint inflammation, and subchondral bone sclerosis [2, 3]. Chondrocytes, as the only cells in the healthy cartilage, play a crucial role in maintaining the balance of the extracellular matrix and tissue homeostasis [4]. Several risk factors such as proinflammatory cytokines and abnormal mechanical stressinduced molecular events (apoptosis, cell death, necrosis, and ECM degradation) in chondrocytes have been reported to be closely correlated with the pathological process of OA [5,6,7]. The functional role and underlying mechanism of miR-24-3p in chondrocyte injury associated with OA remains unknown
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