CCAAT/enhancer binding protein b (C/EBPb) regulates the transcription of growth arrest and DNA damage inducible protein 45 b (GADD45b) in articular chondrocytes.
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 b (GADD45b) is upregulated in chondrocyte clusters in OA cartilage, especially in the early stage of this disease. CCAAT/enhancer binding protein b (C/EBPb) is expressed in the hypertrophic growth plate chondrocytes and functions in synergy with GADD45b. Here, the presence and localization of these proteins was assessed by immunohistochemistry using articular cartilage from OA patients, revealing colocalization of C/EBPb and GADD45b in OA chondrocytes. GADD45b promoter analysis was performed to determine whether C/EBPb directly regulates GADD45b transcription. Furthermore, we analyzed the effect of C/EBPb on Gadd45b gene regulation in articular chondrocytes in vivo and in vitro. Immunohistochemical analysis of C/ebpb haploinsufficient mice (C/ebpb( cartilage showed that C/ebpb haploinsufficiency led to reduced Gadd45b gene expression in these cells. In vitro, we evaluated the effects of conditional C/EBPb overexpression driven by the cartilage oligomeric matrix protein (Comp) promoter in mComp tTA;pTRE Tight BI DsRed mC/ebpb transgenic mice. C/EBPb overexpression significantly stimulated Gadd45b gene expression in articular chondrocytes. Taken together, our data demonstrate that C/EBPb plays a central role in controlling Gadd45b gene expression in these cells.
Pathology, research and practice