INTS7–ABCD3 Interaction Stimulates the Proliferation and Osteoblastic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells by Suppressing Oxidative Stress

Increased adipocyte and decreased osteoblast differentiation, combined with the ectopic proliferation of bone marrow mesenchymal stem cells (BM-MSCs), represent the primary causes of osteoporosis. The dysregulation of numerous intracellular bioactive factors is responsible for the aberrant different...

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Autores principales:	Yubo Liu, Xiao Yu, Anquan Huang, Xiangxin Zhang, Yijun Wang, Wei Geng, Renjie Xu, Suoyuan Li, Hui He, Bo Zheng, Guangxiang Chen, Yaozeng Xu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	bone marrow mesenchymal stem cells (BM-MSCs) INTS7 ABCD3 proliferation osteoblastic differentiation adipogenic differentiation Physiology QP1-981
Acceso en línea:	https://doaj.org/article/4eeef32868614aa08dfedb91ec649fd5
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spelling	oai:doaj.org-article:4eeef32868614aa08dfedb91ec649fd52021-11-30T10:06:23ZINTS7–ABCD3 Interaction Stimulates the Proliferation and Osteoblastic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells by Suppressing Oxidative Stress1664-042X10.3389/fphys.2021.758607https://doaj.org/article/4eeef32868614aa08dfedb91ec649fd52021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.758607/fullhttps://doaj.org/toc/1664-042XIncreased adipocyte and decreased osteoblast differentiation, combined with the ectopic proliferation of bone marrow mesenchymal stem cells (BM-MSCs), represent the primary causes of osteoporosis. The dysregulation of numerous intracellular bioactive factors is responsible for the aberrant differentiation and growth of BM-MSCs. In this study, we focused on a new stimulative factor, integrator complex subunit 7 (INTS7), and its cooperative protein ATP-binding cassette subfamily D member 3 (ABCD3)/high-density lipoprotein-binding protein (HDLBP) in mouse BM-MSCs. We aimed to uncover the effects of the INTS7–ABCD3/HDLBP interaction on BM-MSC biological behaviors and the potential mechanism underlying these effects. Functional in vitro experiments showed that the suppression of the INTS7–ABCD3 interaction rather than HDLBP could impair BM-MSC proliferation and induce cell apoptosis. Moreover, Alizarin Red S and Oil Red O staining, respectively, revealed that INTS7 and ABCD3 knockdown but not HDLBP knockdown could decrease osteoblastic differentiation and accelerate the adipogenic differentiation of BM-MSCs. Mechanistically, reactive oxygen species (ROS) and histone γ-H2AX quantities significantly increased, whereas the levels of antioxidants declined due to INTS7 and ABCD3 inhibition in BM-MSCs. These findings indicated that the suppression of oxidative stress could be involved in the INTS7/ABCD3 co-regulatory mechanisms for BM-MSC proliferation and differentiation, identifying new potential candidates for osteoporosis therapy.Yubo LiuYubo LiuXiao YuAnquan HuangXiangxin ZhangYijun WangWei GengRenjie XuSuoyuan LiHui HeBo ZhengBo ZhengGuangxiang ChenYaozeng XuFrontiers Media S.A.articlebone marrow mesenchymal stem cells (BM-MSCs)INTS7ABCD3proliferationosteoblastic differentiationadipogenic differentiationPhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bone marrow mesenchymal stem cells (BM-MSCs) INTS7 ABCD3 proliferation osteoblastic differentiation adipogenic differentiation Physiology QP1-981
spellingShingle	bone marrow mesenchymal stem cells (BM-MSCs) INTS7 ABCD3 proliferation osteoblastic differentiation adipogenic differentiation Physiology QP1-981 Yubo Liu Yubo Liu Xiao Yu Anquan Huang Xiangxin Zhang Yijun Wang Wei Geng Renjie Xu Suoyuan Li Hui He Bo Zheng Bo Zheng Guangxiang Chen Yaozeng Xu INTS7–ABCD3 Interaction Stimulates the Proliferation and Osteoblastic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells by Suppressing Oxidative Stress
description	Increased adipocyte and decreased osteoblast differentiation, combined with the ectopic proliferation of bone marrow mesenchymal stem cells (BM-MSCs), represent the primary causes of osteoporosis. The dysregulation of numerous intracellular bioactive factors is responsible for the aberrant differentiation and growth of BM-MSCs. In this study, we focused on a new stimulative factor, integrator complex subunit 7 (INTS7), and its cooperative protein ATP-binding cassette subfamily D member 3 (ABCD3)/high-density lipoprotein-binding protein (HDLBP) in mouse BM-MSCs. We aimed to uncover the effects of the INTS7–ABCD3/HDLBP interaction on BM-MSC biological behaviors and the potential mechanism underlying these effects. Functional in vitro experiments showed that the suppression of the INTS7–ABCD3 interaction rather than HDLBP could impair BM-MSC proliferation and induce cell apoptosis. Moreover, Alizarin Red S and Oil Red O staining, respectively, revealed that INTS7 and ABCD3 knockdown but not HDLBP knockdown could decrease osteoblastic differentiation and accelerate the adipogenic differentiation of BM-MSCs. Mechanistically, reactive oxygen species (ROS) and histone γ-H2AX quantities significantly increased, whereas the levels of antioxidants declined due to INTS7 and ABCD3 inhibition in BM-MSCs. These findings indicated that the suppression of oxidative stress could be involved in the INTS7/ABCD3 co-regulatory mechanisms for BM-MSC proliferation and differentiation, identifying new potential candidates for osteoporosis therapy.
format	article
author	Yubo Liu Yubo Liu Xiao Yu Anquan Huang Xiangxin Zhang Yijun Wang Wei Geng Renjie Xu Suoyuan Li Hui He Bo Zheng Bo Zheng Guangxiang Chen Yaozeng Xu
author_facet	Yubo Liu Yubo Liu Xiao Yu Anquan Huang Xiangxin Zhang Yijun Wang Wei Geng Renjie Xu Suoyuan Li Hui He Bo Zheng Bo Zheng Guangxiang Chen Yaozeng Xu
author_sort	Yubo Liu
title	INTS7–ABCD3 Interaction Stimulates the Proliferation and Osteoblastic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells by Suppressing Oxidative Stress
title_short	INTS7–ABCD3 Interaction Stimulates the Proliferation and Osteoblastic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells by Suppressing Oxidative Stress
title_full	INTS7–ABCD3 Interaction Stimulates the Proliferation and Osteoblastic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells by Suppressing Oxidative Stress
title_fullStr	INTS7–ABCD3 Interaction Stimulates the Proliferation and Osteoblastic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells by Suppressing Oxidative Stress
title_full_unstemmed	INTS7–ABCD3 Interaction Stimulates the Proliferation and Osteoblastic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells by Suppressing Oxidative Stress
title_sort	ints7–abcd3 interaction stimulates the proliferation and osteoblastic differentiation of mouse bone marrow mesenchymal stem cells by suppressing oxidative stress
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4eeef32868614aa08dfedb91ec649fd5
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INTS7–ABCD3 Interaction Stimulates the Proliferation and Osteoblastic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells by Suppressing Oxidative Stress

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