STAT3 Up-Regulation Reverses the Effect of NCOR1 on the Hindrance of Osteoclastogenesis

Abstract

Background: Osteoclast formation serves as a triggering factor during osteoarthritis (OA), therefore, our study aimed to elucidate the influence of nuclear receptor corepressor 1 (NCOR1) on osteoclast differentiation and formation. Methods: At days 0, 1, 3, or 5 of osteoclast differentiation, osteoclasts were quantified using tartrate-resistant acid phosphatase (TRAP) staining assay, and their apoptosis rate was assessed employing flow cytometry. Moreover, the protein levels of c-Src, β3-integrin, matrix metalloproteinase 9 (MMP9), NCOR1, histone deacetylase 3 (HDAC3), and signal transducer and activator of transcription 3 (STAT3) were measured by western blot analysis. Additionally, the acetylation of STAT3 during the differentiation of osteoclast precursor (OCP) cells was examined through chromatin immunoprecipitation assay. Furthermore, following the transfection of NCOR1 and STAT3 overexpression, the mechanism of NCOR1 in regulating osteoclastogenesis was determined. Results: The number of TRAP-positive cells and the protein levels of osteoclast-specific genes (MMP9, c-Src, and β3-integrin) as well as STAT3 and its acetylation were significantly increased during osteoclast differentiation. However, the protein expression levels of NCOR1 and HDAC3 were substantially decreased. Meanwhile, these outcomes were reversed with overexpression of NCOR1. Furthermore, STAT3 up-regulation reversed the hindering effect of NCOR1 on osteoclastogenesis. Conclusion: NCOR1 inhibits osteoclastogenesis by suppressing STAT3 acetylation, and this effect can be reversed by STAT3 overexpression.