title: Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells.
abstract: Bisphosphonates such as alendronate are antiosteoporotic drugs that inhibit the activity of bone-resorbing osteoclasts and secondarily promote osteoblastic function. Diabetes increases bone-matrix-associated advanced glycation end products (AGEs) that impair bone marrow progenitor cell (BMPC) osteogenic potential and decrease bone quality. Here we investigated thein vitroeffect of alendronate and/or AGEs on the osteoblastogenic, adipogenic, and chondrogenic potential of BMPC isolated from nondiabetic untreated rats. We also evaluated thein vivoeffect of alendronate (administered orally to rats with insulin-deficient Diabetes) on long-bone microarchitecture and BMPC multilineage potential.In vitro, the osteogenesis (Runx2, alkaline phosphatase, type 1 collagen, and mineralization) and chondrogenesis (glycosaminoglycan production) of BMPC were both decreased by AGEs, while coincubation with alendronate prevented these effects. The adipogenesis of BMPC (PPARγ, intracellular triglycerides, and lipase) was increased by AGEs, and this was prevented by coincubation with alendronate.In vivo, experimental Diabetes (a) decreased femoral trabecular bone area, osteocyte density, and osteoclastic TRAP activity; (b) increased bone marrow adiposity; and (c) deregulated BMPC phenotypic potential (increasing adipogenesis and decreasing osteogenesis and chondrogenesis). Orally administered alendronate prevented all these Diabetes-induced effects on bone. Thus, alendronate could improve bone alterations in diabetic rats by preventing the antiosteogenic, antichondrogenic, and proadipocytic effects of AGEs on BMPC.
authors.affiliation: Laboratorio de Investigaciones en Osteopatías y Metabolismo Mineral (LIOMM), Department of Biological Sciences, School of Exact Sciences, National University of La Plata, Calle 47 y 115, 1900 La Plata, Argentina.
authors.forename: Sara Rocío
authors.identifier: 0000-0002-0520-0736
authors.initials: SR
authors.lastname: Chuguransky
authors.affiliation: Laboratorio de Investigaciones en Osteopatías y Metabolismo Mineral (LIOMM), Department of Biological Sciences, School of Exact Sciences, National University of La Plata, Calle 47 y 115, 1900 La Plata, Argentina.
authors.forename: Ana María
authors.identifier: 0000-0002-0191-7094
authors.initials: AM
authors.lastname: Cortizo
authors.affiliation: Laboratorio de Investigaciones en Osteopatías y Metabolismo Mineral (LIOMM), Department of Biological Sciences, School of Exact Sciences, National University of La Plata, Calle 47 y 115, 1900 La Plata, Argentina.
authors.forename: Antonio Desmond
authors.identifier: 0000-0002-9175-6596
authors.initials: AD
authors.lastname: McCarthy
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D019386:Alendronate / Q000008:administration & dosage*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D020219:Chondrogenesis / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats
chemical_list: D017127:Glycation End Products, Advanced; D019386:Alendronate