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Cathepsin K deficiency promotes alveolar bone regeneration by promoting jaw bone marrow mesenchymal stem cells proliferation and differentiation via glycolysis pathway

OBJECTIVES: To clarify the possible role and mechanism of Cathepsin K (CTSK) in alveolar bone regeneration mediated by jaw bone marrow mesenchymal stem cells (JBMMSC). MATERIALS AND METHODS: Tooth extraction models of Ctsk knockout mice (Ctsk (‐/‐)) and their wildtype (WT) littermates were used to i...

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Autores principales: Zhang, Wuyang, Dong, Zhiwei, Li, Dengke, Li, Bei, Liu, Yuan, Zheng, Xueni, Liu, Hui, Zhou, Hongzhi, Hu, Kaijin, Xue, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249792/
https://www.ncbi.nlm.nih.gov/pubmed/34053135
http://dx.doi.org/10.1111/cpr.13058
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author Zhang, Wuyang
Dong, Zhiwei
Li, Dengke
Li, Bei
Liu, Yuan
Zheng, Xueni
Liu, Hui
Zhou, Hongzhi
Hu, Kaijin
Xue, Yang
author_facet Zhang, Wuyang
Dong, Zhiwei
Li, Dengke
Li, Bei
Liu, Yuan
Zheng, Xueni
Liu, Hui
Zhou, Hongzhi
Hu, Kaijin
Xue, Yang
author_sort Zhang, Wuyang
collection PubMed
description OBJECTIVES: To clarify the possible role and mechanism of Cathepsin K (CTSK) in alveolar bone regeneration mediated by jaw bone marrow mesenchymal stem cells (JBMMSC). MATERIALS AND METHODS: Tooth extraction models of Ctsk knockout mice (Ctsk (‐/‐)) and their wildtype (WT) littermates were used to investigate the effect of CTSK on alveolar bone regeneration. The influences of deletion or inhibition of CTSK by odanacatib (ODN) on proliferation and osteogenic differentiation of JBMMSC were assessed by CCK‐8, Western blot and alizarin red staining. To explore the differently expressed genes, RNA from WT and Ctsk(‐/‐) JBMMSC was sent to RNA‐seq. ECAR, glucose consumption and lactate production were measured to identify the effect of Ctsk deficiency or inhibition on glycolysis. At last, we explored whether Ctsk deficiency or inhibition promoted JBMMSC proliferation and osteogenic differentiation through glycolysis. RESULTS: We found out that Ctsk knockout could promote alveolar bone regeneration in vivo. In vitro, we confirmed that both Ctsk knockout and inhibition by ODN could promote proliferation of JBMMSC, up‐regulate expression of Runx2 and ALP, and enhance matrix mineralization. RNA‐seq results showed that coding genes of key enzymes in glycolysis were significantly up‐regulated in Ctsk(‐/‐) JBMMSC, and Ctsk deficiency or inhibition could promote glycolysis in JBMMSC. After blocking glycolysis by 3PO, the effect of Ctsk deficiency or inhibition on JBMMSC’s regeneration was blocked subsequently. CONCLUSIONS: Our findings revealed that Ctsk knockout or inhibition could promote alveolar bone regeneration by enhancing JBMMSC regeneration via glycolysis. These results shed new lights on the regulatory mechanism of CTSK on bone regeneration.
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spelling pubmed-82497922021-07-09 Cathepsin K deficiency promotes alveolar bone regeneration by promoting jaw bone marrow mesenchymal stem cells proliferation and differentiation via glycolysis pathway Zhang, Wuyang Dong, Zhiwei Li, Dengke Li, Bei Liu, Yuan Zheng, Xueni Liu, Hui Zhou, Hongzhi Hu, Kaijin Xue, Yang Cell Prolif Original Articles OBJECTIVES: To clarify the possible role and mechanism of Cathepsin K (CTSK) in alveolar bone regeneration mediated by jaw bone marrow mesenchymal stem cells (JBMMSC). MATERIALS AND METHODS: Tooth extraction models of Ctsk knockout mice (Ctsk (‐/‐)) and their wildtype (WT) littermates were used to investigate the effect of CTSK on alveolar bone regeneration. The influences of deletion or inhibition of CTSK by odanacatib (ODN) on proliferation and osteogenic differentiation of JBMMSC were assessed by CCK‐8, Western blot and alizarin red staining. To explore the differently expressed genes, RNA from WT and Ctsk(‐/‐) JBMMSC was sent to RNA‐seq. ECAR, glucose consumption and lactate production were measured to identify the effect of Ctsk deficiency or inhibition on glycolysis. At last, we explored whether Ctsk deficiency or inhibition promoted JBMMSC proliferation and osteogenic differentiation through glycolysis. RESULTS: We found out that Ctsk knockout could promote alveolar bone regeneration in vivo. In vitro, we confirmed that both Ctsk knockout and inhibition by ODN could promote proliferation of JBMMSC, up‐regulate expression of Runx2 and ALP, and enhance matrix mineralization. RNA‐seq results showed that coding genes of key enzymes in glycolysis were significantly up‐regulated in Ctsk(‐/‐) JBMMSC, and Ctsk deficiency or inhibition could promote glycolysis in JBMMSC. After blocking glycolysis by 3PO, the effect of Ctsk deficiency or inhibition on JBMMSC’s regeneration was blocked subsequently. CONCLUSIONS: Our findings revealed that Ctsk knockout or inhibition could promote alveolar bone regeneration by enhancing JBMMSC regeneration via glycolysis. These results shed new lights on the regulatory mechanism of CTSK on bone regeneration. John Wiley and Sons Inc. 2021-05-30 /pmc/articles/PMC8249792/ /pubmed/34053135 http://dx.doi.org/10.1111/cpr.13058 Text en © 2021 The Authors. Cell Proliferation published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Zhang, Wuyang
Dong, Zhiwei
Li, Dengke
Li, Bei
Liu, Yuan
Zheng, Xueni
Liu, Hui
Zhou, Hongzhi
Hu, Kaijin
Xue, Yang
Cathepsin K deficiency promotes alveolar bone regeneration by promoting jaw bone marrow mesenchymal stem cells proliferation and differentiation via glycolysis pathway
title Cathepsin K deficiency promotes alveolar bone regeneration by promoting jaw bone marrow mesenchymal stem cells proliferation and differentiation via glycolysis pathway
title_full Cathepsin K deficiency promotes alveolar bone regeneration by promoting jaw bone marrow mesenchymal stem cells proliferation and differentiation via glycolysis pathway
title_fullStr Cathepsin K deficiency promotes alveolar bone regeneration by promoting jaw bone marrow mesenchymal stem cells proliferation and differentiation via glycolysis pathway
title_full_unstemmed Cathepsin K deficiency promotes alveolar bone regeneration by promoting jaw bone marrow mesenchymal stem cells proliferation and differentiation via glycolysis pathway
title_short Cathepsin K deficiency promotes alveolar bone regeneration by promoting jaw bone marrow mesenchymal stem cells proliferation and differentiation via glycolysis pathway
title_sort cathepsin k deficiency promotes alveolar bone regeneration by promoting jaw bone marrow mesenchymal stem cells proliferation and differentiation via glycolysis pathway
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249792/
https://www.ncbi.nlm.nih.gov/pubmed/34053135
http://dx.doi.org/10.1111/cpr.13058
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