ArticlePloS one2016
P2X7R-Panx1 Complex Impairs Bone Mechanosignaling under High Glucose Levels Associated with Type-1 Diabetes.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- Panx1 and P2X7R are associated with impaired skeletal health and delayed bone development in early onset of type 1 diabetes.Frontiers in endocrinology · 2026Article
- Mechanosignaling in Osteoporosis: When Cells Feel the Force.International journal of molecular sciences · 2025Review
- Adenosine diphosphate released from stressed cells triggers mitochondrial transfer to achieve tissue homeostasis.PLoS biology · 2024Article
- Bone health in young adults with type 1 diabetes and progressive eGFR decline.Clinical diabetes and endocrinology · 2024Article
- Bone remodeling and responsiveness to mechanical stimuli in individuals with type 1 diabetes mellitus.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
- Loss of the auxiliary αJBMR plus · 2024Article
- Sclerostin as a new target of diabetes-induced osteoporosis.Frontiers in endocrinology · 2024Review
- Glucose increases proliferation and chemoresistance in chronic myeloid leukemia via decreasing antioxidant Properties of ω-3 polyunsaturated fatty acids in the presence of Iron.Molecular biology reports · 2023Article
- Bone mineral slows down breast cancer cells.Nature biomedical engineering · 2023Article
- Bone mineralisation and glucose metabolism.Current opinion in endocrine and metabolic research · 2023Review
- The Impact of Plasma Membrane Ion Channels on Bone Remodeling in Response to Mechanical Stress, Oxidative Imbalance, and Acidosis.Antioxidants (Basel, Switzerland) · 2023Review
- Fluid flow shear stress and tissue remodeling-an orthodontic perspective: evidence synthesis and differential gene expression network analysis.Frontiers in bioengineering and biotechnology · 2023Article
- Extracellular ATP and its derivatives provide spatiotemporal guidance for bone adaptation to wide spectrum of physical forces.Bone reports · 2022Review
- Biochemical Markers of Bone Turnover in Older Adults With Type 1 Diabetes.The Journal of clinical endocrinology and metabolism · 2022Article
- ATP transporters in the joints.Purinergic signalling · 2021Review
- Purinergic P2 Receptors: Novel Mediators of Mechanotransduction.Frontiers in pharmacology · 2021Review
- Osteocytes and Diabetes: Altered Function of Diabetic Osteocytes.Current osteoporosis reports · 2020Review
- Article
- Mechanosensitive Vaginal Epithelial Adenosine Triphosphate Release and Pannexin 1 Channels in Healthy, in Type 1 Diabetic, and in Surgically Castrated Female Mice.The journal of sexual medicine · 2020Article
- Elevated HbA1c Is Associated with Altered Cortical and Trabecular Microarchitecture in Girls with Type 1 Diabetes.The Journal of clinical endocrinology and metabolism · 2020Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Type 1 diabetes (T1D) causes a range of skeletal problems, including reduced bone density and increased risk for bone fractures. However, mechanisms underlying skeletal complications in diabetes are still not well understood. We hypothesize that high glucose levels in T1D alters expression and function of purinergic receptors (P2Rs) and pannexin 1 (Panx1) channels, and thereby impairs ATP signaling that is essential for proper bone response to mechanical loading and maintenance of skeletal integrity. We first established a key role for P2X7 receptor-Panx1 in osteocyte mechanosignaling by showing that these proteins are co-expressed to provide a major pathway for flow-induced ATP release. To simulate in vitro the glucose levels to which bone cells are exposed in healthy vs. diabetic bones, we cultured osteoblast and osteocyte cell lines for 10 days in medium containing 5.5 or 25 mM glucose. High glucose effects on expression and function of P2Rs and Panx1 channels were determined by Western Blot analysis, quantification of Ca2+ responses to P2R agonists and oscillatory fluid shear stress (± 10 dyne/cm(2)), and measurement of flow-induced ATP release. Diabetic C57BL/6J-Ins2Akita mice were used to evaluate in vivo effects of high glucose on P2R and Panx1. Western blotting indicated altered P2X7R, P2Y2R and P2Y4R expression in high glucose exposed bone cells, and in diabetic bone tissue. Moreover, high glucose blunted normal P2R- and flow-induced Ca2+ signaling and ATP release from osteocytes. These findings indicate that T1D impairs load-induced ATP signaling in osteocytes and affects osteoblast function, which are essential for maintaining bone health.
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