Osteoblast apoptosis is induced by an advanced glycation enproduct
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The present study was carried out to determine whether an advanced glycation product, carboxymethyl lysine modified collagen (CML-collagen), could stimulate apoptosis of osteoblastic cells. In vitro CML-collagen stimulated a dose- and time-dependent increase in apoptosis in primary human adult osteoblastic cells. It also stimulated apoptosis to a similar degree in primary cultures of rat calvarial osteoblastic and MC3T3-E1 cells. However,the maximum induction was less than that induced by TNF-[alpha]. When primary neonatal calvarial osteoblasts or MC3T3E-1 cells were incubated under conditions that promote differentiation, the level of apoptosis stimulated by CML-collagen was higher in differentiated compared to less differentiated osteoblasts. CML-collagen stimulated a significant increase in caspase-3 and -8 activities and to a lesser extent, caspase-9 activity.That the predominant apoptotic pathway invoIved caspase-8 activation of caspase-3 was shown by use of specific inhibitors. When osteoblastic cells were exposed to a chronic low dose exposure to CML-collagen there was a higher degree of apoptosis than exposure to a short-term incubation at a higher dose. Given the impact of premature osteoblast apoptosis on limiting bone formation, these results suggest that AGEs could contribute to diabetic complications associated with inadequate bone formation including diabetic osteopenia, impaired fracture repair and diabetes aggravated periodontal disease.
PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact email@example.com.Thesis (MSD)--Boston University, Goldman School of Dental Medicine, 2006 (Endodontics).Includes bibliographical references: leaves 55-66.
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