@article{Hu2026, 
author = {Shaoyu Hu and Bingquan Li and Jianfeng Ouyang and Yue Meng and Jian Ji and Xiaofei Zheng and Yongheng Ye},
title = {USP29 Represses the Osteoclastic Differentiation of Human CD14+ Peripheral Blood Mononuclear Cells by Stabilizing MafB},
year = {2026},
journal = {BIOCELL},
volume = {50},
number = {2},
pages = {9},
keywords = {MAF bZIP transcription factor B (MafB), osteoclast differentiation, peripheral blood mononuclear cell, ubiquitin-specific protease, USP29, CD14+},
url = {https://www.sciopen.com/article/10.32604/biocell.2026.071651},
doi = {10.32604/biocell.2026.071651},
abstract = {ObjectivesDysregulated 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.MethodsWe constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs, measuring changes in luciferase activity. The identified USP was overexpressed in human CD14+ 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.ResultsOverexpression of ubiquitin-specific protease 29 (USP29) significantly increased MafB expression by approximately 75% (p < 0.0001). Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14+ PBMCs (p < 0.0001). USP29 was found to interact with MafB, markedly reducing its ubiquitination and subsequent degradation in PBMCs (p < 0.001). Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.ConclusionUSP29 acts as a potent stabilizer of MafB, inhibiting osteoclastogenesis in human CD14+ 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.}
}