Morphological changes induced by advanced glycation endproducts in osteoblastic cells: Effects of co-incubation with alendronate

Abstract

Advanced glycation endproducts (AGEs) accumulate with age in various tissues, and are further increased in patients with Diabetes mellitus, in which they are believed to contribute to the development and progression of chronic complications that include a decrease in bone quality. Bisphosphonates are anti-osteoporotic drugs that have been used for the treatment of patients with diabetic bone alterations, although with contradictory results. In the present study, we have evaluated the in vitro alterations on osteoblastic morphology by environmental scanning electron microscopy, in actin cytoskeleton and apoptosis induced by AGEs, as well as the modulation of these effects by alendronate (an N-containing bisphosphonate). Our present results provide evidence for disruption induced by AGEs of the osteoblastic actin cytoskeleton (geodesic domes) and significant alterations in cell morphology with a decrease in cell-substratum interactions leading to an increase in apoptosis of osteoblasts and a decrease in osteoblastic proliferation. High concentrations of alendronate (10−5 M, such as could be expected in an osteoclastic lacuna) further increase osteoblastic morphological and cytoskeletal alterations. However, low doses of alendronate (10−8 M, compatible with extracellular fluid levels to which an osteoblast could be exposed for most of its life cycle) do not affect cell morphology, and in addition are able to prevent AGEs-induced alterations and consequently apoptosis of osteoblasts.