Int J Biol Sci 2023; 19(3):936-949. doi:10.7150/ijbs.78174 This issue Cite

Research Paper

NLRP3 Regulates Mandibular Healing through Interaction with UCHL5 in MSCs

Wenhua Zhao1,2*, Yanan Cao1,2*, Yue Chen1, Yuyi Chen1, Tianxiao Wang1, Lu Li1, Yan Xu1, Hua Yuan1, Hua Wang1, Ruixia Wang2✉, Wen Sun1✉

1. Department of Basic Science of Stomatology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China.
2. Department of Dental Implantology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China.
*These authors contributed equally to this work.

Citation:
Zhao W, Cao Y, Chen Y, Chen Y, Wang T, Li L, Xu Y, Yuan H, Wang H, Wang R, Sun W. NLRP3 Regulates Mandibular Healing through Interaction with UCHL5 in MSCs. Int J Biol Sci 2023; 19(3):936-949. doi:10.7150/ijbs.78174. https://www.ijbs.com/v19p0936.htm
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Abstract

Graphic abstract

NLRP3 has been involved in several physiological and pathological processes. However, the role and mechanism of NLRP3 activation in mandibular healing remain unclear. Here, a full-thickness mandibular defect model by osteotomy was established in wild-type (WT) and Prx1-Cre/ROSAnTnG mice to demonstrate the NLRP3 inflammasome activation in mandibular healing. We found that NLRP3 was activated in mesenchymal stem cells (MSCs)-mediated mandibular healing and was prominent in Prx1+ cells. Inhibition of NLRP3 exerted a positive effect on bone formation without changing the number of Prx1-cre+ 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.

Keywords: Deubiquitination, mandibular healing, mesenchymal stem cells, NLRP3, UCHL5


Citation styles

APA
Zhao, W., Cao, Y., Chen, Y., Chen, Y., Wang, T., Li, L., Xu, Y., Yuan, H., Wang, H., Wang, R., Sun, W. (2023). NLRP3 Regulates Mandibular Healing through Interaction with UCHL5 in MSCs. International Journal of Biological Sciences, 19(3), 936-949. https://doi.org/10.7150/ijbs.78174.

ACS
Zhao, W.; Cao, Y.; Chen, Y.; Chen, Y.; Wang, T.; Li, L.; Xu, Y.; Yuan, H.; Wang, H.; Wang, R.; Sun, W. NLRP3 Regulates Mandibular Healing through Interaction with UCHL5 in MSCs. Int. J. Biol. Sci. 2023, 19 (3), 936-949. DOI: 10.7150/ijbs.78174.

NLM
Zhao W, Cao Y, Chen Y, Chen Y, Wang T, Li L, Xu Y, Yuan H, Wang H, Wang R, Sun W. NLRP3 Regulates Mandibular Healing through Interaction with UCHL5 in MSCs. Int J Biol Sci 2023; 19(3):936-949. doi:10.7150/ijbs.78174. https://www.ijbs.com/v19p0936.htm

CSE
Zhao W, Cao Y, Chen Y, Chen Y, Wang T, Li L, Xu Y, Yuan H, Wang H, Wang R, Sun W. 2023. NLRP3 Regulates Mandibular Healing through Interaction with UCHL5 in MSCs. Int J Biol Sci. 19(3):936-949.

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