Pharmacological blockade of PCAF ameliorates osteoarthritis development via dual inhibition of TNF-α-driven inflammation and ER stress

摘要: Abstract Background Epigenetic mechanisms have been reported to play key roles in osteoarthritis (OA) development. P300/CBP-associated factor (PCAF) is a member of the histone acetyltransferases, which exhibits strong relationship with endoplasmic reticulum (ER) stress and transcription nuclear kappa B (NF-κB) signals. Salidroside, natural acetylation inhibitor, showed its anti-inflammatory anti-apoptotic effects lipopolysaccharide (LPS)-stimulated microglia cells our previous study. However, whether Sal has protective effect against OA remains unknown, relationships PCAF, NF-κB, ER pathway should be explored further. Methods We identified role PCAF pathogenesis determined chondroprotective on both tumor necrosis alpha (TNF-α)-treated human chondrocytes destabilized medial meniscus (DMM) mouse model. Findings found increased expression cartilage TNF-α-driven chondrocytes. Meanwhile, silencing attenuated p65 C/EBP homologous protein levels upon TNF-α stimulation. Furthermore, was specifically bind inhibitory site structure, subsequently reversed TNF-α-induced activation NF-κB signal stress-related apoptosis In addition, as well inflammatory- markers were also observed DMM Interpretation Pharmacological blockade by ameliorates development via inhibition inflammation stress, makes promising therapeutic agents for treatment OA.