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Augmentation of Bone Regeneration by Depletion of Stress-Induced Senescent Cells Using Catechin and Senolytics

Despite advances in bone regenerative medicine, the relationship between stress-induced premature senescence (SIPS) in cells and bone regeneration remains largely unknown. Herein, we demonstrated that the implantation of a lipopolysaccharide (LPS) sustained-release gelatin sponge (LS-G) increases th...

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Autores principales: Honda, Yoshitomo, Huang, Anqi, Tanaka, Tomonari, Han, Xiaoyu, Gao, Beiyuan, Liu, Haitao, Wang, Xinchen, Zhao, Jianxin, Hashimoto, Yoshiya, Yamamoto, Kazuyo, Matsumoto, Naoyuki, Baba, Shunsuke, Umeda, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352429/
https://www.ncbi.nlm.nih.gov/pubmed/32545756
http://dx.doi.org/10.3390/ijms21124213
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author Honda, Yoshitomo
Huang, Anqi
Tanaka, Tomonari
Han, Xiaoyu
Gao, Beiyuan
Liu, Haitao
Wang, Xinchen
Zhao, Jianxin
Hashimoto, Yoshiya
Yamamoto, Kazuyo
Matsumoto, Naoyuki
Baba, Shunsuke
Umeda, Makoto
author_facet Honda, Yoshitomo
Huang, Anqi
Tanaka, Tomonari
Han, Xiaoyu
Gao, Beiyuan
Liu, Haitao
Wang, Xinchen
Zhao, Jianxin
Hashimoto, Yoshiya
Yamamoto, Kazuyo
Matsumoto, Naoyuki
Baba, Shunsuke
Umeda, Makoto
author_sort Honda, Yoshitomo
collection PubMed
description Despite advances in bone regenerative medicine, the relationship between stress-induced premature senescence (SIPS) in cells and bone regeneration remains largely unknown. Herein, we demonstrated that the implantation of a lipopolysaccharide (LPS) sustained-release gelatin sponge (LS-G) increases the number of SIPS cells and that the elimination of these cells promotes bone formation in critical-sized bone defects in the rat calvaria. Histological (hematoxylin–eosin and SA-β-gal) and immunohistological (p16 and p21 for analyzing cellular senescence and 4-HNE for oxidation) staining was used to identify SIPS cells and elucidate the underlying mechanism. Bone formation in defects were analyzed using microcomputed tomography, one and four weeks after surgery. Parallel to LS-G implantation, local epigallocatechin gallate (EGCG) administration, and systemic senolytic (dasatinib and quercetin: D+Q) administration were used to eliminate SIPS cells. After LS-G implantation, SA-β-gal-, p16-, and p21-positive cells (SIPS cells) accumulated in the defects. However, treatment with LS-G+EGCG and LS-G+D+Q resulted in lower numbers of SIPS cells than that with LS-G in the defects, resulting in an augmentation of newly formed bone. We demonstrated that SIPS cells induced by sustained stimulation by LPS may play a deleterious role in bone formation. Controlling these cell numbers is a promising strategy to increase bone regeneration.
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spelling pubmed-73524292020-07-15 Augmentation of Bone Regeneration by Depletion of Stress-Induced Senescent Cells Using Catechin and Senolytics Honda, Yoshitomo Huang, Anqi Tanaka, Tomonari Han, Xiaoyu Gao, Beiyuan Liu, Haitao Wang, Xinchen Zhao, Jianxin Hashimoto, Yoshiya Yamamoto, Kazuyo Matsumoto, Naoyuki Baba, Shunsuke Umeda, Makoto Int J Mol Sci Communication Despite advances in bone regenerative medicine, the relationship between stress-induced premature senescence (SIPS) in cells and bone regeneration remains largely unknown. Herein, we demonstrated that the implantation of a lipopolysaccharide (LPS) sustained-release gelatin sponge (LS-G) increases the number of SIPS cells and that the elimination of these cells promotes bone formation in critical-sized bone defects in the rat calvaria. Histological (hematoxylin–eosin and SA-β-gal) and immunohistological (p16 and p21 for analyzing cellular senescence and 4-HNE for oxidation) staining was used to identify SIPS cells and elucidate the underlying mechanism. Bone formation in defects were analyzed using microcomputed tomography, one and four weeks after surgery. Parallel to LS-G implantation, local epigallocatechin gallate (EGCG) administration, and systemic senolytic (dasatinib and quercetin: D+Q) administration were used to eliminate SIPS cells. After LS-G implantation, SA-β-gal-, p16-, and p21-positive cells (SIPS cells) accumulated in the defects. However, treatment with LS-G+EGCG and LS-G+D+Q resulted in lower numbers of SIPS cells than that with LS-G in the defects, resulting in an augmentation of newly formed bone. We demonstrated that SIPS cells induced by sustained stimulation by LPS may play a deleterious role in bone formation. Controlling these cell numbers is a promising strategy to increase bone regeneration. MDPI 2020-06-13 /pmc/articles/PMC7352429/ /pubmed/32545756 http://dx.doi.org/10.3390/ijms21124213 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Honda, Yoshitomo
Huang, Anqi
Tanaka, Tomonari
Han, Xiaoyu
Gao, Beiyuan
Liu, Haitao
Wang, Xinchen
Zhao, Jianxin
Hashimoto, Yoshiya
Yamamoto, Kazuyo
Matsumoto, Naoyuki
Baba, Shunsuke
Umeda, Makoto
Augmentation of Bone Regeneration by Depletion of Stress-Induced Senescent Cells Using Catechin and Senolytics
title Augmentation of Bone Regeneration by Depletion of Stress-Induced Senescent Cells Using Catechin and Senolytics
title_full Augmentation of Bone Regeneration by Depletion of Stress-Induced Senescent Cells Using Catechin and Senolytics
title_fullStr Augmentation of Bone Regeneration by Depletion of Stress-Induced Senescent Cells Using Catechin and Senolytics
title_full_unstemmed Augmentation of Bone Regeneration by Depletion of Stress-Induced Senescent Cells Using Catechin and Senolytics
title_short Augmentation of Bone Regeneration by Depletion of Stress-Induced Senescent Cells Using Catechin and Senolytics
title_sort augmentation of bone regeneration by depletion of stress-induced senescent cells using catechin and senolytics
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352429/
https://www.ncbi.nlm.nih.gov/pubmed/32545756
http://dx.doi.org/10.3390/ijms21124213
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