tRF16 affects NFKBIA stability and promotes osteoarthritis progression by regulating ALKBH5 expression in m6A-dependent manner

This study aimed to investigate explore the role of tRF16-ALKBH5 in osteoarthritis (OA). Differential expression of tRF in normal and OA tissues was analyzed using sequencing. OA rats model was established by destabilization of the medial meniscus and anterior cruciate ligament transaction surgeries. The tRF-16 inhibitor or mimic was injected into OA rats and OA symptoms were analyzed. We analyzed the m6A levels in tRF16 inhibitor-treated rat cartilage tissues, ALKBH5 levels, and the binding relationship between tRF16 and ALKBH5. The effect of ALKBH5 on OA rats was analyzed using specific antagonists. Chondrocytes were extracted to establish an OA cell model using IL-1β induction. The effects of tRF16, ALKBH5, and downstream genes on chondrocyte viability were verified. tRF-16 was overexpressed in OA patients and rat models. tRF16 inhibitor improved the symptoms of OA rats and inhibited autophagy and extracellular matrix degradation in IL-1β-induced chondrocytes. tRF16 reduced ALKBH5 expression by targeting ALKBH5, decreased NFKBIA mRNA stability, and activated the NF-kB pathway, thus exacerbating OA progression. Collectively, by binding to ALKBH5, tRF16 promotes the degradation of ALKBH5 and impairs the maintenance of NFKBIA mRNA stability by ALKBH5, promotes the nuclear translocation of phos-p65, leads to the secretion of inflammatory factors, exacerbates OA symptoms.