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• mmu_piR_037459 inhibited the expression of collagen II in chondrocytes, inhibited the proliferation of chondrocytes and promoted the apoptosis of chondrocytes. • mmu_piR_037459 affects the function of chondrocytes by regulating the expression of USP7. • Inhibition of mmu_piR_037459 expression could promote chondrocyte proliferation, inhibit chondrocyte apoptosis, and alleviate the degeneration of OA cartilage. Osteoarthritis (OA) is a prevalent chronic degenerative joint ailment. Its primary pathological characteristics encompass degeneration of articular cartilage, inflammation of the synovium, and alterations in the subchondral bone proximate to the cartilage. Chondrocytes, as the sole cell type within articular cartilage, assume a crucial role in upholding the dynamic equilibrium between anabolic and catabolic processes within the extracellular matrix of articular cartilage. IL-1β stands as a pivotal inflammatory factor that instigates cartilage degeneration. piRNA, categorized as a subset of brief non-coding RNAs spanning nucleotide lengths of 26-31nt, assumes a significant regulatory role in cellular function. Small RNA sequencing and quantitative PCR (qPCR) were employed to investigate the impact of the inflammatory factor IL-1β on piRNA expression within chondrocytes. The regulation of mmu_piR_037459 expression in chondrocytes was achieved using piRNA mimics and inhibitors. Additionally, collagen II expression was assessed through both qPCR and Western blot analysis. Chondrocyte apoptosis was evaluated via flow cytometry and clonogenesis assays. To assess the influence of mmu_piR_037459 on osteoarthritis, a mouse model of anterior cruciate ligament transection (ACLT) was established. Furthermore, the regulatory effect of mmu_piR_037459 on USP7 was investigated using bioinformatics and a luciferase reporter gene assay. mmu_piR_037459 inhibited the expression of collagen II in chondrocytes, inhibited the proliferation of chondrocytes, and promoted the apoptosis of chondrocytes. mmu_piR_037459 affected the function of chondrocytes by regulating the expression of USP7. Inhibition of mmu_piR_037459 expression could promote chondrocyte proliferation, inhibit chondrocyte apoptosis, and alleviate the degeneration of OA cartilage. This study suggests that mmu_piR_037459 maybe a new therapeutic targets and strategies for the treatment of OA. [ABSTRACT FROM AUTHOR]