FEBS Letters · 2014 · 96 citations · 34 references
Life SciencesImmunologyMolecular BiologyCartilage RepairGene ExpressionInflammationCartilage BreakdownCartilage DegenerationCartilage MetabolismMicrorna BiologyMicrorna-mediated RegulationOsteoarthritisCartilage Breakdown PathophysiologyCartilage Degradation MechanismsCartilage DestructionCartilage Extracellular Matrix HomeostasisDecapentaplegic SignalingDownstream Gene RegulationInterleukin-1 Beta PathwayInterleukin-1 Beta Signaling
MicroRNA-145 has been shown to regulate chondrocyte homeostasis. It seems that miR-145 is implicated in cartilage dysfunction in Osteoarthritis (OA). However, the functional role of miR-145 in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage has never been clarified. Here, we show that miR-145 expression increased in OA chondrocytes and in response to IL-1β stimulation. We confirm that mothers against decapentaplegic homolog 3 (Smad3), a key factor in maintaining chondrocyte homeostasis, is directly regulated by miR-145. Modulation of miR-145 affects the expression of Smad3 causing a change of its downstream target gene expression as well as IL-1β-induced ECM degradation in OA chondrocytes. This indicates that miR-145 contributes to impaired ECM in OA cartilage probably in part via targeting Smad3.
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