Fig. 6

The role of BRD4 in the mechanical stress-induced TMJ OA pathological changes and inflammatory response of chondrocytes. The excessive mechanical stress is an important etiological factor of TMJ OA. It can cause cartilage thinning, subchondral bone destruction, and joint inflammation. BRD4 inhibition can alleviate the TMJ pathological changes induced by mechanical stress. The underlying mechanism is shown in the schematic diagram of the chondrocyte. At the cellular level, the binding of BRD4 to the promoter region of the inflammation-related genes and microRNA increased under mechanical stress stimulation. We confirmed the binding enhanced the transcription of Trem1 and inflammatory factors such as Il-1β, Tnf-α, and Il-6. After these receptor and inflammatory factors are expressed, they aggravated the inflammatory response of the chondrocytes. IL-1β-induced inflammation is TREM1-dependent, and both IL-1β and TREM1 are regulated by BRD4. Our study indicates that BRD4 plays an important role in mechanical stress-induced TMJ pathological changes and especially cartilage inflammatory response. TREM1 is involved in the BRD4’s epigenetic regulation of inflammation