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Comparison of Necroptosis With Apoptosis for OVX-Induced Osteoporosis

As one common kind of osteoporosis, postmenopausal osteoporosis (PMOP) is associated with the death and excessive loss of osteocytes. Estrogen deficiency of PMOP can cause osteocyte death by regulating necroptosis and apoptosis, but their roles in POMP have not been compared. In the present study, o...

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Autores principales: He, Bin, Zhu, Yongjun, Cui, Hongwang, Sun, Bo, Su, Tian, Wen, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8740137/
https://www.ncbi.nlm.nih.gov/pubmed/35004853
http://dx.doi.org/10.3389/fmolb.2021.790613
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author He, Bin
Zhu, Yongjun
Cui, Hongwang
Sun, Bo
Su, Tian
Wen, Peng
author_facet He, Bin
Zhu, Yongjun
Cui, Hongwang
Sun, Bo
Su, Tian
Wen, Peng
author_sort He, Bin
collection PubMed
description As one common kind of osteoporosis, postmenopausal osteoporosis (PMOP) is associated with the death and excessive loss of osteocytes. Estrogen deficiency of PMOP can cause osteocyte death by regulating necroptosis and apoptosis, but their roles in POMP have not been compared. In the present study, ovariectomy (OVX)-induced rat and murine long bone osteocyte Y4 (MLO-Y4) cells were used to compare the influence of necroptosis and apoptosis on osteocyte death and bone loss. Benzyloxycarbonyl-Val-Ala-Asp (zVAD) and necrostatin-1 (Nec-1) were used to specifically block cell apoptosis and necroptosis, respectively. OVX rats and MLO-Y4 cells were divided into zVAD group, Nec-1 group, zVAD + Nec-1 group, vehicle, and control group. The tibial plateaus of the rat model were harvested at 8 weeks after OVX and were analyzed by micro–computed tomography, transmission electron microscopy (TEM), the transferase dUTP nick end labeling assay, and western blot. The death of MLO-Y4 was stimulated by TNF-α and was measured by flow cytometry and TEM. The results found that necroptosis and apoptosis were both responsible for the death and excessive loss of osteocytes, as well as bone loss in OVX-induced osteoporosis, and furthermore necroptosis may generate greater impact on the death of osteocytes than apoptosis. Necroptotic death of osteocytes was mainly regulated by the receptor-interacting protein kinase 3 signaling pathway. Collectively, inhibition of necroptosis may produce better efficacy in reducing osteocyte loss than that of apoptosis, and combined blockade of necroptosis and apoptosis provide new insights into preventing and treating PMOP.
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spelling pubmed-87401372022-01-08 Comparison of Necroptosis With Apoptosis for OVX-Induced Osteoporosis He, Bin Zhu, Yongjun Cui, Hongwang Sun, Bo Su, Tian Wen, Peng Front Mol Biosci Molecular Biosciences As one common kind of osteoporosis, postmenopausal osteoporosis (PMOP) is associated with the death and excessive loss of osteocytes. Estrogen deficiency of PMOP can cause osteocyte death by regulating necroptosis and apoptosis, but their roles in POMP have not been compared. In the present study, ovariectomy (OVX)-induced rat and murine long bone osteocyte Y4 (MLO-Y4) cells were used to compare the influence of necroptosis and apoptosis on osteocyte death and bone loss. Benzyloxycarbonyl-Val-Ala-Asp (zVAD) and necrostatin-1 (Nec-1) were used to specifically block cell apoptosis and necroptosis, respectively. OVX rats and MLO-Y4 cells were divided into zVAD group, Nec-1 group, zVAD + Nec-1 group, vehicle, and control group. The tibial plateaus of the rat model were harvested at 8 weeks after OVX and were analyzed by micro–computed tomography, transmission electron microscopy (TEM), the transferase dUTP nick end labeling assay, and western blot. The death of MLO-Y4 was stimulated by TNF-α and was measured by flow cytometry and TEM. The results found that necroptosis and apoptosis were both responsible for the death and excessive loss of osteocytes, as well as bone loss in OVX-induced osteoporosis, and furthermore necroptosis may generate greater impact on the death of osteocytes than apoptosis. Necroptotic death of osteocytes was mainly regulated by the receptor-interacting protein kinase 3 signaling pathway. Collectively, inhibition of necroptosis may produce better efficacy in reducing osteocyte loss than that of apoptosis, and combined blockade of necroptosis and apoptosis provide new insights into preventing and treating PMOP. Frontiers Media S.A. 2021-12-24 /pmc/articles/PMC8740137/ /pubmed/35004853 http://dx.doi.org/10.3389/fmolb.2021.790613 Text en Copyright © 2021 He, Zhu, Cui, Sun, Su and Wen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
He, Bin
Zhu, Yongjun
Cui, Hongwang
Sun, Bo
Su, Tian
Wen, Peng
Comparison of Necroptosis With Apoptosis for OVX-Induced Osteoporosis
title Comparison of Necroptosis With Apoptosis for OVX-Induced Osteoporosis
title_full Comparison of Necroptosis With Apoptosis for OVX-Induced Osteoporosis
title_fullStr Comparison of Necroptosis With Apoptosis for OVX-Induced Osteoporosis
title_full_unstemmed Comparison of Necroptosis With Apoptosis for OVX-Induced Osteoporosis
title_short Comparison of Necroptosis With Apoptosis for OVX-Induced Osteoporosis
title_sort comparison of necroptosis with apoptosis for ovx-induced osteoporosis
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8740137/
https://www.ncbi.nlm.nih.gov/pubmed/35004853
http://dx.doi.org/10.3389/fmolb.2021.790613
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