@Article{biocell.2026.071651,
AUTHOR = {Shaoyu Hu, Bingquan Li, Jianfeng Ouyang, Yue Meng, Jian Ji, Xiaofei Zheng, Yongheng Ye},
TITLE = {USP29 Represses the Osteoclastic Differentiation of Human CD14<sup>+</sup> Peripheral Blood Mononuclear Cells by Stabilizing MafB},
JOURNAL = {BIOCELL},
VOLUME = {50},
YEAR = {2026},
NUMBER = {2},
PAGES = {0--0},
URL = {http://www.techscience.com/biocell/v50n2/66243},
ISSN = {1667-5746},
ABSTRACT = { <b>Objectives:</b> Dysregulated osteoclast function contributes to skeletal diseases. However, the specific ubiquitination regulators of the osteoclastogenesis repressor MafB, particularly at the post-translational level, remain undefined. This study aims to identify ubiquitin-specific proteases (USPs) that deubiquitinate MafB and enhance its stability. <b>Methods:</b> We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs, measuring changes in luciferase activity. The identified USP was overexpressed in human CD14<sup>+</sup> peripheral blood mononuclear cells (PBMCs) to evaluate its effect. Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V (CD51) staining and Western blot analysis. Co-immunoprecipitation (co-IP) was performed to assess the interplay. The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot. Finally, MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation. <b>Results:</b> Overexpression of ubiquitin-specific protease 29 (USP29) significantly increased MafB expression by approximately 75% (<i>p</i> < 0.0001). Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14<sup>+</sup> PBMCs (<i>p</i> < 0.0001). USP29 was found to interact with MafB, markedly reducing its ubiquitination and subsequent degradation in PBMCs (<i>p</i> < 0.001). Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis. <b>Conclusion:</b> USP29 acts as a potent stabilizer of MafB, inhibiting osteoclastogenesis in human CD14<sup>+</sup> PBMCs, at least in part, by enhancing MafB stability. These findings expand our understanding of USP29’s role and the post-translational regulation of MafB. Furthermore, USP29 serves as a vital factor that controls osteoclast differentiation, and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.},
DOI = {10.32604/biocell.2026.071651}
}