NLRP3 Regulates Mandibular Healing through Interaction with UCHL5 in MSCs
Wenhua Zhao, Yanan Cao, Yue Chen, Yuyi Chen, Tianxiao Wang, Lu Li, Yan Xu, Hua Yuan, Hua Wang, Ruixia Wang, Wen Sun
Abstract
cells in the defect areas. In addition, NLRP3 deficiency promoted osteoblast differentiation. We next screened for the deubiquitinating enzymes that were previously reported to be associated with NLRP3, and identified UCHL5 as a regulator of NLRP3 activation in mandibular healing. Mechanistically, NLRP3 directly bound to UCHL5 and maintained its stability through reducing ubiquitin-proteasome pathway degradation in mandibular MSCs. At last, UCHL5 inhibition enhanced osteoblast differentiation by promoting NLRP3 ubiquitination and degradation. Thus, our results provided the proof that NLRP3 acted as a negative modulator in mandibular healing and extended the current knowledge regarding posttranslational modification of NLRP3 by UCHL5.