TRIM15 mediates ubiquitination and degradation of HOXD11 to promote IL-1β-induced chondrocyte injury

Background Osteoarthritis (OA) is a degenerative joint disease characterized mainly by cartilage degeneration, with a global incidence of approximately 3.6%. Homeobox D11 (HOXD11) is downregulated in OA cartilage and is associated with OA progression. Objectives The aim of this study was to explore the impact of HOXD11 on IL-1β-induced chondrocyte injury. Methods The cell counting kit-8 assay was employed to detect cell viability. The western blot assay was used to evaluate the levels of target proteins and transfection efficiency in cells. Lactate dehydrogenase release was detected using a lactate dehydrogenase detection kit. The apoptosis rate of cells was detected by flow cytometry. The secretion of inflammatory factors in the cell culture supernatant and cells was detected by enzyme-linked immunosorbent assay, qRT-PCR and western blot. Co-immunoprecipitation was used to detect ubiquitination modification. Results HOXD11 was lowly expressed and tripartite motif containing 15 (TRIM15) was highly expressed in interleukin-1β (IL-1β)-induced ATDC5 cells. Overexpression of HOXD11 could inhibit IL-1β-induced apoptosis and release of inflammatory factors in ATDC5 cells. Mechanistically, TRIM15 could mediate the ubiquitination modification and degradation of HOXD11, thereby accelerating IL-1β-induced ATDC5 cell injury. Conclusions TRIM15 promotes IL-1β-induced chondrocyte damage by mediating the ubiquitination modification and degradation of HOXD11, which might provide a potential strategy for the treatment of OA.