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Reduced APPL1 impairs osteogenic differentiation of mesenchymal stem cells by facilitating MGP expression to disrupt the BMP2 pathway in osteoporosis

An imbalance of human mesenchymal stem cells (MSCs) adipogenic and osteogenic differentiation plays an important role in the pathogenesis of osteoporosis. Our previous study verified that Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1)/myoferlin deficiency pr...

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Autores principales: Yuan, Weiquan, Liu, Wenjie, Zhang, Yunhui, Wang, Xinglang, Xu, Chenhao, Li, Quanfeng, Ji, Pengfei, Wang, Jiaxin, Feng, Pei, Wu, Yanfeng, Shen, Huiyong, Wang, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10318529/
https://www.ncbi.nlm.nih.gov/pubmed/37187293
http://dx.doi.org/10.1016/j.jbc.2023.104823
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author Yuan, Weiquan
Liu, Wenjie
Zhang, Yunhui
Wang, Xinglang
Xu, Chenhao
Li, Quanfeng
Ji, Pengfei
Wang, Jiaxin
Feng, Pei
Wu, Yanfeng
Shen, Huiyong
Wang, Peng
author_facet Yuan, Weiquan
Liu, Wenjie
Zhang, Yunhui
Wang, Xinglang
Xu, Chenhao
Li, Quanfeng
Ji, Pengfei
Wang, Jiaxin
Feng, Pei
Wu, Yanfeng
Shen, Huiyong
Wang, Peng
author_sort Yuan, Weiquan
collection PubMed
description An imbalance of human mesenchymal stem cells (MSCs) adipogenic and osteogenic differentiation plays an important role in the pathogenesis of osteoporosis. Our previous study verified that Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1)/myoferlin deficiency promotes adipogenic differentiation of MSCs by blocking autophagic flux in osteoporosis. However, the function of APPL1 in the osteogenic differentiation of MSCs remains unclear. This study aimed to investigate the role of APPL1 in the osteogenic differentiation of MSCs in osteoporosis and the underlying regulatory mechanism. In this study, we demonstrated the downregulation of APPL1 expression in patients with osteoporosis and osteoporosis mice. The severity of clinical osteoporosis was negatively correlated with the expression of APPL1 in bone marrow MSCs. We found that APPL1 positively regulates the osteogenic differentiation of MSCs in vitro and in vivo. Moreover, RNA sequencing showed that the expression of MGP, an osteocalcin/matrix Gla family member, was significantly upregulated after APPL1 knockdown. Mechanistically, our study showed that reduced APPL1 impaired the osteogenic differentiation of mesenchymal stem cells by facilitating Matrix Gla protein expression to disrupt the BMP2 pathway in osteoporosis. We also evaluated the significance of APPL1 in promoting osteogenesis in a mouse model of osteoporosis. These results suggest that APPL1 may be an important target for the diagnosis and treatment of osteoporosis.
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spelling pubmed-103185292023-07-05 Reduced APPL1 impairs osteogenic differentiation of mesenchymal stem cells by facilitating MGP expression to disrupt the BMP2 pathway in osteoporosis Yuan, Weiquan Liu, Wenjie Zhang, Yunhui Wang, Xinglang Xu, Chenhao Li, Quanfeng Ji, Pengfei Wang, Jiaxin Feng, Pei Wu, Yanfeng Shen, Huiyong Wang, Peng J Biol Chem Research Article An imbalance of human mesenchymal stem cells (MSCs) adipogenic and osteogenic differentiation plays an important role in the pathogenesis of osteoporosis. Our previous study verified that Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1)/myoferlin deficiency promotes adipogenic differentiation of MSCs by blocking autophagic flux in osteoporosis. However, the function of APPL1 in the osteogenic differentiation of MSCs remains unclear. This study aimed to investigate the role of APPL1 in the osteogenic differentiation of MSCs in osteoporosis and the underlying regulatory mechanism. In this study, we demonstrated the downregulation of APPL1 expression in patients with osteoporosis and osteoporosis mice. The severity of clinical osteoporosis was negatively correlated with the expression of APPL1 in bone marrow MSCs. We found that APPL1 positively regulates the osteogenic differentiation of MSCs in vitro and in vivo. Moreover, RNA sequencing showed that the expression of MGP, an osteocalcin/matrix Gla family member, was significantly upregulated after APPL1 knockdown. Mechanistically, our study showed that reduced APPL1 impaired the osteogenic differentiation of mesenchymal stem cells by facilitating Matrix Gla protein expression to disrupt the BMP2 pathway in osteoporosis. We also evaluated the significance of APPL1 in promoting osteogenesis in a mouse model of osteoporosis. These results suggest that APPL1 may be an important target for the diagnosis and treatment of osteoporosis. American Society for Biochemistry and Molecular Biology 2023-05-13 /pmc/articles/PMC10318529/ /pubmed/37187293 http://dx.doi.org/10.1016/j.jbc.2023.104823 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Yuan, Weiquan
Liu, Wenjie
Zhang, Yunhui
Wang, Xinglang
Xu, Chenhao
Li, Quanfeng
Ji, Pengfei
Wang, Jiaxin
Feng, Pei
Wu, Yanfeng
Shen, Huiyong
Wang, Peng
Reduced APPL1 impairs osteogenic differentiation of mesenchymal stem cells by facilitating MGP expression to disrupt the BMP2 pathway in osteoporosis
title Reduced APPL1 impairs osteogenic differentiation of mesenchymal stem cells by facilitating MGP expression to disrupt the BMP2 pathway in osteoporosis
title_full Reduced APPL1 impairs osteogenic differentiation of mesenchymal stem cells by facilitating MGP expression to disrupt the BMP2 pathway in osteoporosis
title_fullStr Reduced APPL1 impairs osteogenic differentiation of mesenchymal stem cells by facilitating MGP expression to disrupt the BMP2 pathway in osteoporosis
title_full_unstemmed Reduced APPL1 impairs osteogenic differentiation of mesenchymal stem cells by facilitating MGP expression to disrupt the BMP2 pathway in osteoporosis
title_short Reduced APPL1 impairs osteogenic differentiation of mesenchymal stem cells by facilitating MGP expression to disrupt the BMP2 pathway in osteoporosis
title_sort reduced appl1 impairs osteogenic differentiation of mesenchymal stem cells by facilitating mgp expression to disrupt the bmp2 pathway in osteoporosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10318529/
https://www.ncbi.nlm.nih.gov/pubmed/37187293
http://dx.doi.org/10.1016/j.jbc.2023.104823
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