Divergent effects of Diabetes on the osteoblastic differentiation of vascular smooth muscle cells and bone marrow progenitor cells. Role of advanced glycation end products

SEDLINSKY, CLAUDIA; FERNANDEZ JM; MOLINUEVO, MARÍA SILVINA; SCHURMAN L; CORTIZO AM; MCCARTHY A

Congreso; The Endocrine Society´s ENDO 2013; 2013

Type 2 Diabetes has been associated with increased vascular calcification of the tunica media in arteries, as well as with bone fragility. We have previously demonstrated that advanced glycation end products (AGEs) which accumulate in diabetic tissues, have deleterious actions on osteoblasts in culture. In this study we evaluated the hypothesis that Diabetes can differentially affect the osteogenic potential of bone marrow progenitor cells (BMPC) and vascular smooth muscle cells (VSMC), and that these effects could be mediated by AGEs. BMPC and VSMC were obtained from non-diabetic (control) and insulin-deficient diabetic Sprague-Dawley adult rats. After 15 days of osteogenic differentiation, BMPC from diabetic animals (BMPCd) expressed lower levels of osteoblastic markers compared to control BMPC: alkaline phosphatase (ALP, 4.7±0.4 vs 10±1 nmol pNP/mg Protein/min p=0.01), type I collagen (Col I, 72±6 vs 100±1 ug/mg Protein p=0.01) and extracellular mineralization (Min, 78±6 vs 100±6 % basal p=0.01). Moreover, the incubation of BMPCd with 100 ug/ml AGEs caused a further impairment in osteoblastic differentiation compared to control BMPC incubated with AGEs (ALP: 3±0.1 vs 6±1 p=0.05; Col I: 60±3 vs 80±1 p=0.01; Min: 62±3 vs 85±1 p=0.01). On the contrary, after 7 days of culture in osteogenic media VSMC from diabetic animals (VSMCd) expressed higher levels of of osteoblastic markers compared to control VSMC: Col I (137±11 vs 106±7 ug/mg Protein p=0.01) and Min (130±5 vs 100±4 % basal p=0.01). This behavior persisted and was potentiated by incubation with 100 ug/ml AGEs (VSMCd: ALP: 8.6±0.2; Col I: 171±5; Min:170±6 and control VSMC: ALP: 7.0±0.6; Col I: 164±7; Min: 144±10). Moreover, VSMCd cultured for 7 days in non-osteogenic media showed a tendency to express higher levels of these osteoblastic markers than control VSMC. In conclusion, our results show that Diabetes causes a decrease on the osteogenic potential of BMPC but an increase in the osteoblastic differentiation of VSMC. Both actions are potentiated by an excess of AGEs in the culture media, suggesting a unifying mechanism for these divergent effects.