ROLE OF PARATHYROID HORMONE-RELATED PROTEIN (PTHRP) ON THE ALTERED BONE FORMATION IN A MOUSE MODEL OF DIABETIC OSTEOPENIA (EORS AWARD WINNER 2008)

Type 1 diabetes mellitus (DM) is associated with a decreased bone formation. Osteoblastic expression of parathyroid hormone-related protein(PTHrP) -an important modulator of osteoblast differentiation- decreases in age-related osteopenia. We here examined the putative role of PTHrP on the decreased osteoblastic function in DM. We performed marrow ablation in the tibiae of diabetic mice after streptozotocin injection (glycemia >300mg/dl). Some mice were treated with PTHrP(1–36) (100 ng/g/every other day, s.c.) or vehicle for 2 weeks. Both tibiae were then removed for histological evaluation or total RNA isolation. In vitro, MC3T3-E1 cells were grown in differentiation medium (a-MEM), with or without high glucose(HG) (25 mM) (or mannitol, as osmotic control), supplemented (or not) with PTHrP(1–36) (100 nM). In some experiments, anti-PTHrP N-terminal antibody C13 (1:100) or PTHrP(7–34) (1 μM) were added to normal-glucose medium. RANKL secretion was measured in the cell-conditioned medium by ELISA. Gene expression was analyzed by real-time PCR. DM induced a 10–15% weight loss and a decrease (20–40%;p In conclusion, a deficit in PTHrP production by osteoblasts seems to be at least in part responsible for the DM-related decreased bone formation in mice.