title: Diabetes Stimulates Osteoclastogenesis by Acidosis-Induced Activation of Transient Receptor Potential Cation Channels.
abstract: Patients with type 1 diabetes have lower bone mineral density and higher risk of fractures. The role of osteoblasts in diabetes-related osteoporosis is well acknowledged whereas the role of osteoclasts (OCLs) is still unclear. We hypothesize that OCLs participate in pathological bone remodeling. We conducted studies in animals (streptozotocin-induced type 1 diabetic mice) and cellular models to investigate canonical and non-canonical mechanisms underlying excessive OCL activation. Diabetic mice show an increased number of active OCLs. In vitro studies demonstrate the involvement of acidosis in OCL activation and the implication of transient receptor potential cation channel subfamily V member 1 (TRPV1). In vivo studies confirm the establishment of local acidosis in the diabetic bone marrow (BM) as well as the ineffectiveness of insulin in correcting the pH variation and osteoclast activation. Conversely, treatment with TRPV1 receptor antagonists re-establishes a physiological OCL availability. These data suggest that diabetes causes local acidosis in the BM that in turn increases osteoclast activation through the modulation of TRPV1. The use of clinically available TRPV1 antagonists may provide a new means to combat bone problems associated with diabetes.
authors.affiliation: Division of Experimental Cardiovascular Medicine, Bristol Heart Institute, University of Bristol, UK.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Reni
authors.affiliation: Division of Experimental Cardiovascular Medicine, Bristol Heart Institute, University of Bristol, UK.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mangialardi
authors.affiliation: Vascular Pathology and Regeneration, Bristol Heart Institute, University of Bristol, UK.|University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, UK.
authors.forename: Marco
authors.initials: M
authors.lastname: Meloni
authors.affiliation: Division of Experimental Cardiovascular Medicine, Bristol Heart Institute, University of Bristol, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Madeddu
mesh_terms: D000138:Acidosis / Q000150:complications*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D006801:Humans; D051379:Mice; D010012:Osteogenesis; D010024:Osteoporosis / Q000209:etiology* / Q000503:physiopathology*; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
chemical_list: D050051:Transient Receptor Potential Channels