Enhancement of Bone-Forming Ability on Beta-Tricalcium Phosphate by Modulating Cellular Senescence Mechanisms Using Senolytics

Various stresses latently induce cellular senescence that occasionally deteriorates the functioning of surrounding tissues. Nevertheless, little is known about the appearance and function of senescent cells, caused by the implantation of beta-tricalcium phosphate (β-TCP)—used widely in dentistry and...

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Autores principales:	Xinchen Wang, Yoshitomo Honda, Jianxin Zhao, Hidetoshi Morikuni, Aki Nishiura, Yoshiya Hashimoto, Naoyuki Matsumoto
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cellular senescence beta-tricalcium phosphate bone formation senolytics Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/44478f9704d74679b80099589aa762c4
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spelling	oai:doaj.org-article:44478f9704d74679b80099589aa762c42021-11-25T17:56:24ZEnhancement of Bone-Forming Ability on Beta-Tricalcium Phosphate by Modulating Cellular Senescence Mechanisms Using Senolytics10.3390/ijms2222124151422-00671661-6596https://doaj.org/article/44478f9704d74679b80099589aa762c42021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12415https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Various stresses latently induce cellular senescence that occasionally deteriorates the functioning of surrounding tissues. Nevertheless, little is known about the appearance and function of senescent cells, caused by the implantation of beta-tricalcium phosphate (β-TCP)—used widely in dentistry and orthopedics for treating bone diseases. In this study, two varying sizes of β-TCP granules (<300 μm and 300–500 μm) were implanted, and using histological and immunofluorescent staining, appearances of senescent-like cells in critical-sized bone defects in the calvaria of Sprague Dawley rats were evaluated. Parallelly, bone formation in defects was investigated with or without the oral administration of senolytics (a cocktail of dasatinib and quercetin). A week after the implantation, the number of senescence-associated beta-galactosidase, p21-, p19-, and tartrate-resistant acid phosphatase-positive cells increased and then decreased upon administrating senolytics. This administration of senolytics also attenuated 4-hydroxy-2-nonenal staining, representing reactive oxygen species. Combining senolytic administration with β-TCP implantation significantly enhanced the bone formation in defects as revealed by micro-computed tomography analysis and hematoxylin-eosin staining. This study demonstrates that β-TCP granules latently induce senescent-like cells, and senolytic administration may improve the bone-forming ability of β-TCP by inhibiting senescence-associated mechanisms.Xinchen WangYoshitomo HondaJianxin ZhaoHidetoshi MorikuniAki NishiuraYoshiya HashimotoNaoyuki MatsumotoMDPI AGarticlecellular senescencebeta-tricalcium phosphatebone formationsenolyticsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12415, p 12415 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cellular senescence beta-tricalcium phosphate bone formation senolytics Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	cellular senescence beta-tricalcium phosphate bone formation senolytics Biology (General) QH301-705.5 Chemistry QD1-999 Xinchen Wang Yoshitomo Honda Jianxin Zhao Hidetoshi Morikuni Aki Nishiura Yoshiya Hashimoto Naoyuki Matsumoto Enhancement of Bone-Forming Ability on Beta-Tricalcium Phosphate by Modulating Cellular Senescence Mechanisms Using Senolytics
description	Various stresses latently induce cellular senescence that occasionally deteriorates the functioning of surrounding tissues. Nevertheless, little is known about the appearance and function of senescent cells, caused by the implantation of beta-tricalcium phosphate (β-TCP)—used widely in dentistry and orthopedics for treating bone diseases. In this study, two varying sizes of β-TCP granules (<300 μm and 300–500 μm) were implanted, and using histological and immunofluorescent staining, appearances of senescent-like cells in critical-sized bone defects in the calvaria of Sprague Dawley rats were evaluated. Parallelly, bone formation in defects was investigated with or without the oral administration of senolytics (a cocktail of dasatinib and quercetin). A week after the implantation, the number of senescence-associated beta-galactosidase, p21-, p19-, and tartrate-resistant acid phosphatase-positive cells increased and then decreased upon administrating senolytics. This administration of senolytics also attenuated 4-hydroxy-2-nonenal staining, representing reactive oxygen species. Combining senolytic administration with β-TCP implantation significantly enhanced the bone formation in defects as revealed by micro-computed tomography analysis and hematoxylin-eosin staining. This study demonstrates that β-TCP granules latently induce senescent-like cells, and senolytic administration may improve the bone-forming ability of β-TCP by inhibiting senescence-associated mechanisms.
format	article
author	Xinchen Wang Yoshitomo Honda Jianxin Zhao Hidetoshi Morikuni Aki Nishiura Yoshiya Hashimoto Naoyuki Matsumoto
author_facet	Xinchen Wang Yoshitomo Honda Jianxin Zhao Hidetoshi Morikuni Aki Nishiura Yoshiya Hashimoto Naoyuki Matsumoto
author_sort	Xinchen Wang
title	Enhancement of Bone-Forming Ability on Beta-Tricalcium Phosphate by Modulating Cellular Senescence Mechanisms Using Senolytics
title_short	Enhancement of Bone-Forming Ability on Beta-Tricalcium Phosphate by Modulating Cellular Senescence Mechanisms Using Senolytics
title_full	Enhancement of Bone-Forming Ability on Beta-Tricalcium Phosphate by Modulating Cellular Senescence Mechanisms Using Senolytics
title_fullStr	Enhancement of Bone-Forming Ability on Beta-Tricalcium Phosphate by Modulating Cellular Senescence Mechanisms Using Senolytics
title_full_unstemmed	Enhancement of Bone-Forming Ability on Beta-Tricalcium Phosphate by Modulating Cellular Senescence Mechanisms Using Senolytics
title_sort	enhancement of bone-forming ability on beta-tricalcium phosphate by modulating cellular senescence mechanisms using senolytics
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/44478f9704d74679b80099589aa762c4
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Enhancement of Bone-Forming Ability on Beta-Tricalcium Phosphate by Modulating Cellular Senescence Mechanisms Using Senolytics

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