title: Effects of glucose and its modulation by insulin and estradiol on BMSC differentiation into osteoblastic lineages.
abstract: It is well known that diabetes affects bone in human and animal models, and leads to osteopenia and osteoporosis. Bone-mineral density and other biochemical markers of bone turnover are very much affected in people with diabetes. Reduced bone mass, occurring with increased frequency in diabetes mellitus, has been attributed to poor glycemic control, but the pathogenic mechanisms remain unknown. High concentrations of glucose (hyperglycemia) in diabetics leads to this complication. Very few in vitro studies using bone-cell lines have been carried out to address this problem. In this study, we examined the effects of different doses of glucose concentration (5.5, 16.5, and 49.4 mmol/L), alone, with insulin (0.6 microg/mL), or with 17beta-estradiol (E2) (10 nmol/L), on rat bone-marrow stromal cells (BMSCs) in the presence of an osteogenic medium. BMSC proliferation and alkaline phosphatase (ALP) were studied after 3 and 7 d of culture, respectively; the area stained for collagen and mineralized nodules was studied after 28 d of culture. With high concentrations of glucose, BMSC proliferation, ALP activity, the number of nodules formed, and the area stained for collagen were greatly reduced. Insulin treatment alone was able to increase [3H]-thymidine uptake or ALP activity, whereas both insulin and estradiol were able to increase the number of mineralized nodules and the area stained for collagen and mineralization. In conclusion, this study suggests that insulin and estradiol are able to contain the deleterious effect of high concentrations of glucose on BMSC-derived osteoblast proliferation and function.
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, India.
authors.forename: V
authors.initials: V
authors.lastname: Gopalakrishnan
authors.forename: R C
authors.initials: RC
authors.lastname: Vignesh
authors.forename: J
authors.initials: J
authors.lastname: Arunakaran
authors.forename: M M
authors.initials: MM
authors.lastname: Aruldhas
authors.forename: N
authors.initials: N
authors.lastname: Srinivasan
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
chemical_list: D007328:Insulin; D014316:Tritium; D004958:Estradiol; D000469:Alkaline Phosphatase; D005947:Glucose; D013936:Thymidine