In vivo effects of strontium ranelate on bone marrow progenitor cells of diabetic rats

Abstract

Chronic diabetes mellitus (DM) is associated with a reduction in bone mineral content (osteopenia and osteoporosis). The object of this study was to evaluate the in vivo effect of the anti-osteoporotic drug strontium ranelate (SrRa) administered orally to control and diabetic animals, on the osteogenic potential of bone marrow progenitor cells (BMPC). Sixteen young male Wistar rats were divided into two groups: control (C) and diabetic with partial beta-cell destruction via consecutive intra-peritoneal injections of nicotinamide and streptozotocin (D). Seven days post-injection, each group was sub-divided: without treatment, or oral treatment with SrRa (625 mg/kg/day) for six weeks, after which the animals were euthanised (groups C, C+SrRa, D, D+SrRa). BMPC were obtained from rats of all four groups by flushing of the diaphysary canal (humerus and/or femur). Adherent cells were then cultured until confluence in DMEM-10% FBS. Cell proliferation was evaluated with the MTT mitogenic bioassay. BMPC were replated and incubated in an osteogenic medium for 14 days (determination of alkaline phosphatase [ALP] and type-1 collagen) or 21 days (evaluation of mineralisation). BMPC from C+SrRa rats showed a significant increase versus control in proliferation (133%) and in osteogenic differentiation (collagen 143%, ALP 168%, mineralisation 117%). Induction of diabetes (group D) significantly decreased the proliferation and osteoblastic differentiation of BMPC. Treatment of diabetic animals with SrRa (group D+SrRa) completely prevented these anti-osteogenic effects of Diabetes. Thus in our experimental in vivo model, Diabetes decreases the osteogenic potential of BMPC, an effect that can be prevented by oral treatment with strontium ranelate.