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Autophagy Maintains the Function of Bone Marrow Mesenchymal Stem Cells to Prevent Estrogen Deficiency-Induced Osteoporosis

Rationale: The impaired function of endogenous bone marrow mesenchymal stem cells (BMMSCs) is a determinant in the development of osteoporosis (OP). Recent researches have proved that autophagy plays an important role in maintenance of skeletal phenotype. However, whether autophagy affects the devel...

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Autores principales: Qi, Meng, Zhang, Liqiang, Ma, Yang, Shuai, Yi, Li, Liya, Luo, Kefu, Liu, Wenjia, Jin, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695145/
https://www.ncbi.nlm.nih.gov/pubmed/29158841
http://dx.doi.org/10.7150/thno.17949
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author Qi, Meng
Zhang, Liqiang
Ma, Yang
Shuai, Yi
Li, Liya
Luo, Kefu
Liu, Wenjia
Jin, Yan
author_facet Qi, Meng
Zhang, Liqiang
Ma, Yang
Shuai, Yi
Li, Liya
Luo, Kefu
Liu, Wenjia
Jin, Yan
author_sort Qi, Meng
collection PubMed
description Rationale: The impaired function of endogenous bone marrow mesenchymal stem cells (BMMSCs) is a determinant in the development of osteoporosis (OP). Recent researches have proved that autophagy plays an important role in maintenance of skeletal phenotype. However, whether autophagy affects the development of OP through regulating the function of BMMSCs remains elusive. Methods: Ovariectomy (OVX)-induced OP model and sham model were established in 8-week-old C57 mice. The differentiation and immunoregulation properties of BMMSCs from two models were examined by osteogenic/adipogenic induction in vitro and treatment of a dextran sulfate sodium (DSS)-induced mice colitis model in vivo. We evaluated autophagy activity in sham and OVX BMMSCs by quantitative real time-polymerase chain reaction (qRT-PCR), western blotting, laser confocal microscopy and transmission electron microscopy (TEM). Finally, to testify the effects of rapamycin, short hairpin RNA (shRNA) -BECN1 (shBECN1) and shRNA-ATG5 (shATG5), we performed Alizarin Red staining and Oil Red O staining to detect lineage differentiations of BMMSCs, and carried out micro-CT, calcein staining and Oil Red O staining to assess the skeletal phenotype. Results: BMMSCs from OVX-induced OP model mice exhibited decreased osteogenic differentiation, increased adipogenic differentiation and impaired immunoregulatory capacity. Furthermore, autophagy decreased both in bone marrow and BMMSCs of osteoporotic mice. Importantly, regulation of autophagy directly affects the functions of BMMSCs, including differentiation and immunoregulatory capacities. Moreover, treatment with rapamycin rescued the function of endogenous BMMSCs and attenuated the osteoporotic phenotype in OVX mice. Conclusion: Our findings suggest that autophagy regulates the regenerative function of BMMSCs and controls the development of OP. The restoration of autophagy by rapamycin may provide an effective therapeutic method for osteoporosis.
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spelling pubmed-56951452017-11-20 Autophagy Maintains the Function of Bone Marrow Mesenchymal Stem Cells to Prevent Estrogen Deficiency-Induced Osteoporosis Qi, Meng Zhang, Liqiang Ma, Yang Shuai, Yi Li, Liya Luo, Kefu Liu, Wenjia Jin, Yan Theranostics Research Paper Rationale: The impaired function of endogenous bone marrow mesenchymal stem cells (BMMSCs) is a determinant in the development of osteoporosis (OP). Recent researches have proved that autophagy plays an important role in maintenance of skeletal phenotype. However, whether autophagy affects the development of OP through regulating the function of BMMSCs remains elusive. Methods: Ovariectomy (OVX)-induced OP model and sham model were established in 8-week-old C57 mice. The differentiation and immunoregulation properties of BMMSCs from two models were examined by osteogenic/adipogenic induction in vitro and treatment of a dextran sulfate sodium (DSS)-induced mice colitis model in vivo. We evaluated autophagy activity in sham and OVX BMMSCs by quantitative real time-polymerase chain reaction (qRT-PCR), western blotting, laser confocal microscopy and transmission electron microscopy (TEM). Finally, to testify the effects of rapamycin, short hairpin RNA (shRNA) -BECN1 (shBECN1) and shRNA-ATG5 (shATG5), we performed Alizarin Red staining and Oil Red O staining to detect lineage differentiations of BMMSCs, and carried out micro-CT, calcein staining and Oil Red O staining to assess the skeletal phenotype. Results: BMMSCs from OVX-induced OP model mice exhibited decreased osteogenic differentiation, increased adipogenic differentiation and impaired immunoregulatory capacity. Furthermore, autophagy decreased both in bone marrow and BMMSCs of osteoporotic mice. Importantly, regulation of autophagy directly affects the functions of BMMSCs, including differentiation and immunoregulatory capacities. Moreover, treatment with rapamycin rescued the function of endogenous BMMSCs and attenuated the osteoporotic phenotype in OVX mice. Conclusion: Our findings suggest that autophagy regulates the regenerative function of BMMSCs and controls the development of OP. The restoration of autophagy by rapamycin may provide an effective therapeutic method for osteoporosis. Ivyspring International Publisher 2017-10-12 /pmc/articles/PMC5695145/ /pubmed/29158841 http://dx.doi.org/10.7150/thno.17949 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Qi, Meng
Zhang, Liqiang
Ma, Yang
Shuai, Yi
Li, Liya
Luo, Kefu
Liu, Wenjia
Jin, Yan
Autophagy Maintains the Function of Bone Marrow Mesenchymal Stem Cells to Prevent Estrogen Deficiency-Induced Osteoporosis
title Autophagy Maintains the Function of Bone Marrow Mesenchymal Stem Cells to Prevent Estrogen Deficiency-Induced Osteoporosis
title_full Autophagy Maintains the Function of Bone Marrow Mesenchymal Stem Cells to Prevent Estrogen Deficiency-Induced Osteoporosis
title_fullStr Autophagy Maintains the Function of Bone Marrow Mesenchymal Stem Cells to Prevent Estrogen Deficiency-Induced Osteoporosis
title_full_unstemmed Autophagy Maintains the Function of Bone Marrow Mesenchymal Stem Cells to Prevent Estrogen Deficiency-Induced Osteoporosis
title_short Autophagy Maintains the Function of Bone Marrow Mesenchymal Stem Cells to Prevent Estrogen Deficiency-Induced Osteoporosis
title_sort autophagy maintains the function of bone marrow mesenchymal stem cells to prevent estrogen deficiency-induced osteoporosis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695145/
https://www.ncbi.nlm.nih.gov/pubmed/29158841
http://dx.doi.org/10.7150/thno.17949
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