High Glucose Downregulates Connexin 43 Expression and Its Gap Junction and Hemichannel Function in Osteocyte-like MLO-Y4 Cells Through Activation of the p38MAPK/ERK Signal Pathway

Lei Yang,1 Guangping Zhou,2 Mingyang Li,1 Yan Li,1 Liqing Yang,1 Qin Fu,1 Ye Tian1 1Orthopedics Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China; 2Orthopedics Department, Shenyang Orthopedics Hospital, Shenyang, Liaoning Pr...

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Autores principales:	Yang L, Zhou G, Li M, Li Y, Fu Q, Tian Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	high glucose osteocyte connexin 43 gap junction hemichannel Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/7464f78e8bdf4542925e5f57b55b290b
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spelling	oai:doaj.org-article:7464f78e8bdf4542925e5f57b55b290b2021-12-02T09:15:19ZHigh Glucose Downregulates Connexin 43 Expression and Its Gap Junction and Hemichannel Function in Osteocyte-like MLO-Y4 Cells Through Activation of the p38MAPK/ERK Signal Pathway1178-7007https://doaj.org/article/7464f78e8bdf4542925e5f57b55b290b2020-02-01T00:00:00Zhttps://www.dovepress.com/high-glucose-downregulates-connexin-43-expression-and-its-gap-junction-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Lei Yang,1 Guangping Zhou,2 Mingyang Li,1 Yan Li,1 Liqing Yang,1 Qin Fu,1 Ye Tian1 1Orthopedics Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China; 2Orthopedics Department, Shenyang Orthopedics Hospital, Shenyang, Liaoning Province, People’s Republic of ChinaCorrespondence: Qin Fu Tel +86-18940251086Email fuqsj_hospital@126.comPurpose: Osteocyte network structure correlates with bone material quality. This network is profoundly altered in diabetic mice; however, the underlying mechanisms are unknown. The gap junction protein connexin 43 (Cx43) is necessary for normal osteocyte function and osteocyte network formation. Here, we evaluated Cx43 expression in patients with diabetes, the effect of high glucose on Cx43 expression, and the function of Cx43 gap junctions and hemichannels in osteocyte-like MLO-Y4 (MLO-Y4) cells.Patients and Methods: Human cortical bone samples were obtained from patients with or without type II diabetes mellitus (T2DM) who underwent arthroplasty surgery to treat osteoporosis-induced femoral neck fracture.Cx43 expression was quantified in human cortical bone samples from both groups of patients and MLO-Y4 cells. The functions of Cx43 gap junctions and hemichannels in MLO-Y4 cells were evaluated using dye transfer and dye uptake assays, respectively. Furthermore, we evaluated levels of membrane Cx43 (mCx43), the functional form, and p38MAPK/ERK1/2 signaling, which is involved in mCx43 internalization, to characterize the mechanism of decreased Cx43 expression and gap junctions and hemichannels function.Results: Osteocyte Cx43 expression was decreased in femoral neck cortical bone samples of patients with T2DM patients compared with the non-diabetic control group. In addition, Cx43 expression was decreased in MLO-Y4 cells treated with high glucose. The functions of Cx43 gap junctions and hemichannels were inhibited in MLO-Y4 cells treated with high glucose. mCx43 expression was decreased in response to activation of p38-MAPK/ERK signaling. Inhibition of the p38-MAPK/ERK pathway partially reversed the decreases in Cx43 hemichannels and gap-junctions function.Conclusion: High glucose dampened Cx43 gap junction and hemichannel function in MLO-Y4 cells by activating the p38MAPK/ERK pathway leading to subsequent mCx43 internalization.Keywords: high glucose, osteocyte, connexin 43, gap junction, hemichannelYang LZhou GLi MLi YYang LFu QTian YDove Medical Pressarticlehigh glucoseosteocyteconnexin 43gap junctionhemichannelSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 545-557 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	high glucose osteocyte connexin 43 gap junction hemichannel Specialties of internal medicine RC581-951
spellingShingle	high glucose osteocyte connexin 43 gap junction hemichannel Specialties of internal medicine RC581-951 Yang L Zhou G Li M Li Y Yang L Fu Q Tian Y High Glucose Downregulates Connexin 43 Expression and Its Gap Junction and Hemichannel Function in Osteocyte-like MLO-Y4 Cells Through Activation of the p38MAPK/ERK Signal Pathway
description	Lei Yang,1 Guangping Zhou,2 Mingyang Li,1 Yan Li,1 Liqing Yang,1 Qin Fu,1 Ye Tian1 1Orthopedics Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China; 2Orthopedics Department, Shenyang Orthopedics Hospital, Shenyang, Liaoning Province, People’s Republic of ChinaCorrespondence: Qin Fu Tel +86-18940251086Email fuqsj_hospital@126.comPurpose: Osteocyte network structure correlates with bone material quality. This network is profoundly altered in diabetic mice; however, the underlying mechanisms are unknown. The gap junction protein connexin 43 (Cx43) is necessary for normal osteocyte function and osteocyte network formation. Here, we evaluated Cx43 expression in patients with diabetes, the effect of high glucose on Cx43 expression, and the function of Cx43 gap junctions and hemichannels in osteocyte-like MLO-Y4 (MLO-Y4) cells.Patients and Methods: Human cortical bone samples were obtained from patients with or without type II diabetes mellitus (T2DM) who underwent arthroplasty surgery to treat osteoporosis-induced femoral neck fracture.Cx43 expression was quantified in human cortical bone samples from both groups of patients and MLO-Y4 cells. The functions of Cx43 gap junctions and hemichannels in MLO-Y4 cells were evaluated using dye transfer and dye uptake assays, respectively. Furthermore, we evaluated levels of membrane Cx43 (mCx43), the functional form, and p38MAPK/ERK1/2 signaling, which is involved in mCx43 internalization, to characterize the mechanism of decreased Cx43 expression and gap junctions and hemichannels function.Results: Osteocyte Cx43 expression was decreased in femoral neck cortical bone samples of patients with T2DM patients compared with the non-diabetic control group. In addition, Cx43 expression was decreased in MLO-Y4 cells treated with high glucose. The functions of Cx43 gap junctions and hemichannels were inhibited in MLO-Y4 cells treated with high glucose. mCx43 expression was decreased in response to activation of p38-MAPK/ERK signaling. Inhibition of the p38-MAPK/ERK pathway partially reversed the decreases in Cx43 hemichannels and gap-junctions function.Conclusion: High glucose dampened Cx43 gap junction and hemichannel function in MLO-Y4 cells by activating the p38MAPK/ERK pathway leading to subsequent mCx43 internalization.Keywords: high glucose, osteocyte, connexin 43, gap junction, hemichannel
format	article
author	Yang L Zhou G Li M Li Y Yang L Fu Q Tian Y
author_facet	Yang L Zhou G Li M Li Y Yang L Fu Q Tian Y
author_sort	Yang L
title	High Glucose Downregulates Connexin 43 Expression and Its Gap Junction and Hemichannel Function in Osteocyte-like MLO-Y4 Cells Through Activation of the p38MAPK/ERK Signal Pathway
title_short	High Glucose Downregulates Connexin 43 Expression and Its Gap Junction and Hemichannel Function in Osteocyte-like MLO-Y4 Cells Through Activation of the p38MAPK/ERK Signal Pathway
title_full	High Glucose Downregulates Connexin 43 Expression and Its Gap Junction and Hemichannel Function in Osteocyte-like MLO-Y4 Cells Through Activation of the p38MAPK/ERK Signal Pathway
title_fullStr	High Glucose Downregulates Connexin 43 Expression and Its Gap Junction and Hemichannel Function in Osteocyte-like MLO-Y4 Cells Through Activation of the p38MAPK/ERK Signal Pathway
title_full_unstemmed	High Glucose Downregulates Connexin 43 Expression and Its Gap Junction and Hemichannel Function in Osteocyte-like MLO-Y4 Cells Through Activation of the p38MAPK/ERK Signal Pathway
title_sort	high glucose downregulates connexin 43 expression and its gap junction and hemichannel function in osteocyte-like mlo-y4 cells through activation of the p38mapk/erk signal pathway
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/7464f78e8bdf4542925e5f57b55b290b
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High Glucose Downregulates Connexin 43 Expression and Its Gap Junction and Hemichannel Function in Osteocyte-like MLO-Y4 Cells Through Activation of the p38MAPK/ERK Signal Pathway

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