ArticleDiabetes, metabolic syndrome and obesity : targets and therapy2020
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.
Article in Diabetes, metabolic syndrome and obesity : targets and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Panx1 and P2X7R are associated with impaired skeletal health and delayed bone development in early onset of type 1 diabetes.Frontiers in endocrinology · 2026Article
- New Aspects of the Pathophysiology of Diabetic Bone Fragility - Type 2 Diabetes Mellitus as a Disease of Accelerated Aging.Current osteoporosis reports · 2025Review
- Glucocorticoids Alter Bone Microvascular Barrier via MAPK/Connexin43 Mechanisms.Advanced healthcare materials · 2025Article
- Regulator of G protein signalling 18 promotes osteocyte proliferation by activating the extracellular signal‑regulated kinase signalling pathway.International journal of molecular medicine · 2024Article
- Article
- Targeting strategies for bone diseases: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- Targeting ferroptosis suppresses osteocyte glucolipotoxicity and alleviates diabetic osteoporosis.Bone research · 2022Article
- miRNA-Gene Interaction Network Construction Strategy to Discern Promising Traditional Chinese Medicine against Osteoporosis.BioMed research international · 2022Article
- Characteristics of Ventricular Electrophysiological Substrates in Metabolic Mice Treated with Empagliflozin.International journal of molecular sciences · 2021Article
- Exendin-4, a glucagon-like peptide receptor agonist, facilitates osteoblast differentiation via connexin43.Endocrine · 2021Article
- Glucose-limiting conditions induce an invasive population of MDA-MB-231 breast cancer cells with increased connexin 43 expression and membrane localization.Journal of cell communication and signaling · 2021Article
- 3D Environment Is Required In Vitro to Demonstrate Altered Bone Metabolism Characteristic for Type 2 Diabetics.International journal of molecular sciences · 2021Article
- Osteocytes and Diabetes: Altered Function of Diabetic Osteocytes.Current osteoporosis reports · 2020Review
- Connexin 43 plays a role in proliferation and migration of pulmonary arterial fibroblasts in response to hypoxia.Pulmonary circulationArticle
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeOsteocyte 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
methodsHuman 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.
resultsOsteocyte 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.
conclusionHigh glucose dampened Cx43 gap junction and hemichannel function in MLO-Y4 cells by activating the p38MAPK/ERK pathway leading to subsequent mCx43 internalization.
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