RESUMO
Osteoarthritis (OA) is a whole joint disease characterized by cartilage degradation, which causes pain and disability in older adults. Our previous work showed that growth arrest and DNA damage-inducible protein 45 ß (GADD45ß) is upregulated in chondrocyte clusters in OA cartilage, especially in the early stage of this disease. CCAAT/enhancer binding protein ß (C/EBPß) is expressed in the hypertrophic growth plate chondrocytes and functions in synergy with GADD45ß. Here, the presence and localization of these proteins was assessed by immunohistochemistry using articular cartilage from OA patients, revealing colocalization of C/EBPß and GADD45ß in OA chondrocytes. GADD45ß promoter analysis was performed to determine whether C/EBPß directly regulates GADD45ß transcription. Furthermore, we analyzed the effect of C/EBPß on Gadd45ß gene regulation in articular chondrocytes in vivo and in vitro. Immunohistochemical analysis of C/ebpß-haploinsufficient mice (C/ebpß(+/-)) cartilage showed that C/ebpß haploinsufficiency led to reduced Gadd45ß gene expression in these cells. In vitro, we evaluated the effects of conditional C/EBPß overexpression driven by the cartilage oligomeric matrix protein (Comp) promoter in mComp-tTA;pTRE-Tight-BI-DsRed-mC/ebpß transgenic mice. C/EBPß overexpression significantly stimulated Gadd45ß gene expression in articular chondrocytes. Taken together, our data demonstrate that C/EBPß plays a central role in controlling Gadd45ß gene expression in these cells.
