Interleukin 26 attenuates osteoblast differentiation in osteoarthritis patients by activating COX2 and NF-κB pathways.

Osteoarthritis (OA) represents the prevailing form of degenerative joint pathology. Recent investigations have revealed a heightened expression of interleukin 26 (IL-26) in various inflammatory arthritic conditions, including OA. However, the specific impacts and functions of IL-26 on osteoblasts (OBs) within the context of OA remain inadequately elucidated. This study aims to clarify the effects and underlying mechanisms of IL-26 by examining its influence on osteoblasts isolated from OA patients and a murine osteoblast cell line. Human primary osteoblasts and mouse pre-osteoblast cells were subjected to treatment with β-glycerophosphate or concurrent treatment with IL-26 to observe the effects on osteoblast differentiation. The differentiation of osteoblasts was assessed through the expression of relevant genes using reverse transcription-polymerase chain reaction (RT-PCR). Key molecular mechanisms of downstream signaling pathways were examined through immunoblotting assays. Our results reveal that IL-26 mitigates osteoblast differentiation and reduces the expression of the marker alkaline phosphatase. Furthermore, the NF-κB downstream OB proliferated marker iNOS and inhibition OB differentiated marker LCN2 messenger RNA are up-regulated in IL-26 treated group. Also, phosphorylation and nuclear translocation of NF-κB p65 occur following IL-26 stimulation. Additionally, IL-26 enhances the downstream transcription factor cyclooxygenase-2 (COX2), a major player associated with iNOS. STAT1, the canonical receptor signaling pathway of IL-26 is activated. In summary, our findings substantiate the role of IL-26 in osteoarthritis and identify it as a potential therapeutic target for intervention in osteoarthritic pathology.