Cargando…

USP7 promotes the osteoclast differentiation of CD14+ human peripheral blood monocytes in osteoporosis via HMGB1 deubiquitination

BACKGROUND: Abnormal osteoclast and osteoblast differentiation is an essential pathological process in osteoporosis. As an important deubiquitinase enzyme, ubiquitin-specific peptidase 7 (USP7) participates in various disease processes through posttranslational modification. However, the mechanism b...

Descripción completa

Detalles Bibliográficos
Autores principales: Lin, Yu-Cong, Zheng, Guan, Liu, Hua-Tao, Wang, Peng, Yuan, Wei-Quan, Zhang, Yun-Hui, Peng, Xiao-Shuai, Li, Guo-Jian, Wu, Yan-Feng, Shen, Hui-Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Chinese Speaking Orthopaedic Society 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10275958/
https://www.ncbi.nlm.nih.gov/pubmed/37333461
http://dx.doi.org/10.1016/j.jot.2023.05.007
_version_ 1785059975969636352
author Lin, Yu-Cong
Zheng, Guan
Liu, Hua-Tao
Wang, Peng
Yuan, Wei-Quan
Zhang, Yun-Hui
Peng, Xiao-Shuai
Li, Guo-Jian
Wu, Yan-Feng
Shen, Hui-Yong
author_facet Lin, Yu-Cong
Zheng, Guan
Liu, Hua-Tao
Wang, Peng
Yuan, Wei-Quan
Zhang, Yun-Hui
Peng, Xiao-Shuai
Li, Guo-Jian
Wu, Yan-Feng
Shen, Hui-Yong
author_sort Lin, Yu-Cong
collection PubMed
description BACKGROUND: Abnormal osteoclast and osteoblast differentiation is an essential pathological process in osteoporosis. As an important deubiquitinase enzyme, ubiquitin-specific peptidase 7 (USP7) participates in various disease processes through posttranslational modification. However, the mechanism by which USP7 regulates osteoporosis remains unknown. Herein, we aimed to investigate whether USP7 regulates abnormal osteoclast differentiation in osteoporosis. METHODS: The gene expression profiles of blood monocytes were preprocessed to analyze the differential expression of USP genes. CD14+ peripheral blood mononuclear cells (PBMCs) were isolated from whole blood collected from osteoporosis patients (OPs) and healthy donors (HDs), and the expression pattern of USP7 during the differentiation of CD14+ PBMCs into osteoclasts was detected by western blotting. The role of USP7 in the osteoclast differentiation of PBMCs treated with USP7 siRNA or exogenous rUSP7 was further investigated by the F-actin assay, TRAP staining and western blotting. Moreover, the interaction between high-mobility group protein 1 (HMGB1) and USP7 was investigated by coimmunoprecipitation, and the regulation of the USP7-HMGB1 axis in osteoclast differentiation was further verified. Osteoporosis in ovariectomized (OVX) mice was then studied using the USP7-specific inhibitor P5091 to identify the role of USP7 in osteoporosis. RESULTS: The bioinformatic analyses and CD14+ PBMCs from osteoporosis patients confirmed that the upregulation of USP7 was associated with osteoporosis. USP7 positively regulates the osteoclast differentiation of CD14+ PBMCs in vitro. Mechanistically, USP7 promoted osteoclast formation by binding to and deubiquitination of HMGB1. In vivo, P5091 effectively attenuates bone loss in OVX mice. CONCLUSION: We demonstrate that USP7 promotes the differentiation of CD14+ PBMCs into osteoclasts via HMGB1 deubiquitination and that inhibition of USP7 effectively attenuates bone loss in osteoporosis in vivo. The translational potential of this article:The study reveals novel insights into the role of USP7 in the progression of osteoporosis and provides a new therapeutic target for the treatment of osteoporosis.
format Online
Article
Text
id pubmed-10275958
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Chinese Speaking Orthopaedic Society
record_format MEDLINE/PubMed
spelling pubmed-102759582023-06-18 USP7 promotes the osteoclast differentiation of CD14+ human peripheral blood monocytes in osteoporosis via HMGB1 deubiquitination Lin, Yu-Cong Zheng, Guan Liu, Hua-Tao Wang, Peng Yuan, Wei-Quan Zhang, Yun-Hui Peng, Xiao-Shuai Li, Guo-Jian Wu, Yan-Feng Shen, Hui-Yong J Orthop Translat Original Article BACKGROUND: Abnormal osteoclast and osteoblast differentiation is an essential pathological process in osteoporosis. As an important deubiquitinase enzyme, ubiquitin-specific peptidase 7 (USP7) participates in various disease processes through posttranslational modification. However, the mechanism by which USP7 regulates osteoporosis remains unknown. Herein, we aimed to investigate whether USP7 regulates abnormal osteoclast differentiation in osteoporosis. METHODS: The gene expression profiles of blood monocytes were preprocessed to analyze the differential expression of USP genes. CD14+ peripheral blood mononuclear cells (PBMCs) were isolated from whole blood collected from osteoporosis patients (OPs) and healthy donors (HDs), and the expression pattern of USP7 during the differentiation of CD14+ PBMCs into osteoclasts was detected by western blotting. The role of USP7 in the osteoclast differentiation of PBMCs treated with USP7 siRNA or exogenous rUSP7 was further investigated by the F-actin assay, TRAP staining and western blotting. Moreover, the interaction between high-mobility group protein 1 (HMGB1) and USP7 was investigated by coimmunoprecipitation, and the regulation of the USP7-HMGB1 axis in osteoclast differentiation was further verified. Osteoporosis in ovariectomized (OVX) mice was then studied using the USP7-specific inhibitor P5091 to identify the role of USP7 in osteoporosis. RESULTS: The bioinformatic analyses and CD14+ PBMCs from osteoporosis patients confirmed that the upregulation of USP7 was associated with osteoporosis. USP7 positively regulates the osteoclast differentiation of CD14+ PBMCs in vitro. Mechanistically, USP7 promoted osteoclast formation by binding to and deubiquitination of HMGB1. In vivo, P5091 effectively attenuates bone loss in OVX mice. CONCLUSION: We demonstrate that USP7 promotes the differentiation of CD14+ PBMCs into osteoclasts via HMGB1 deubiquitination and that inhibition of USP7 effectively attenuates bone loss in osteoporosis in vivo. The translational potential of this article:The study reveals novel insights into the role of USP7 in the progression of osteoporosis and provides a new therapeutic target for the treatment of osteoporosis. Chinese Speaking Orthopaedic Society 2023-06-11 /pmc/articles/PMC10275958/ /pubmed/37333461 http://dx.doi.org/10.1016/j.jot.2023.05.007 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Lin, Yu-Cong
Zheng, Guan
Liu, Hua-Tao
Wang, Peng
Yuan, Wei-Quan
Zhang, Yun-Hui
Peng, Xiao-Shuai
Li, Guo-Jian
Wu, Yan-Feng
Shen, Hui-Yong
USP7 promotes the osteoclast differentiation of CD14+ human peripheral blood monocytes in osteoporosis via HMGB1 deubiquitination
title USP7 promotes the osteoclast differentiation of CD14+ human peripheral blood monocytes in osteoporosis via HMGB1 deubiquitination
title_full USP7 promotes the osteoclast differentiation of CD14+ human peripheral blood monocytes in osteoporosis via HMGB1 deubiquitination
title_fullStr USP7 promotes the osteoclast differentiation of CD14+ human peripheral blood monocytes in osteoporosis via HMGB1 deubiquitination
title_full_unstemmed USP7 promotes the osteoclast differentiation of CD14+ human peripheral blood monocytes in osteoporosis via HMGB1 deubiquitination
title_short USP7 promotes the osteoclast differentiation of CD14+ human peripheral blood monocytes in osteoporosis via HMGB1 deubiquitination
title_sort usp7 promotes the osteoclast differentiation of cd14+ human peripheral blood monocytes in osteoporosis via hmgb1 deubiquitination
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10275958/
https://www.ncbi.nlm.nih.gov/pubmed/37333461
http://dx.doi.org/10.1016/j.jot.2023.05.007
work_keys_str_mv AT linyucong usp7promotestheosteoclastdifferentiationofcd14humanperipheralbloodmonocytesinosteoporosisviahmgb1deubiquitination
AT zhengguan usp7promotestheosteoclastdifferentiationofcd14humanperipheralbloodmonocytesinosteoporosisviahmgb1deubiquitination
AT liuhuatao usp7promotestheosteoclastdifferentiationofcd14humanperipheralbloodmonocytesinosteoporosisviahmgb1deubiquitination
AT wangpeng usp7promotestheosteoclastdifferentiationofcd14humanperipheralbloodmonocytesinosteoporosisviahmgb1deubiquitination
AT yuanweiquan usp7promotestheosteoclastdifferentiationofcd14humanperipheralbloodmonocytesinosteoporosisviahmgb1deubiquitination
AT zhangyunhui usp7promotestheosteoclastdifferentiationofcd14humanperipheralbloodmonocytesinosteoporosisviahmgb1deubiquitination
AT pengxiaoshuai usp7promotestheosteoclastdifferentiationofcd14humanperipheralbloodmonocytesinosteoporosisviahmgb1deubiquitination
AT liguojian usp7promotestheosteoclastdifferentiationofcd14humanperipheralbloodmonocytesinosteoporosisviahmgb1deubiquitination
AT wuyanfeng usp7promotestheosteoclastdifferentiationofcd14humanperipheralbloodmonocytesinosteoporosisviahmgb1deubiquitination
AT shenhuiyong usp7promotestheosteoclastdifferentiationofcd14humanperipheralbloodmonocytesinosteoporosisviahmgb1deubiquitination