LIPID OXIDATION-PRODUCTS HAVE OPPOSITE EFFECTS ON CALCIFYING VASCULARCELL AND BONE CELL-DIFFERENTIATION - A POSSIBLE EXPLANATION FOR THE PARADOX OF ARTERIAL CALCIFICATION IN OSTEOPOROTIC PATIENTS

Atherosclerotic calcification and osteoporosis often coexist in patien ts, yielding formation of bone mineral in vascular walls and its simul taneous loss from bone. To assess the potential role of lipoproteins i n both processes, we examined the effects of minimally oxidized low-de nsity lipoprotein (MM-LDL) and several other lipid oxidation products on calcifying vascular cells (CVCs) and bone-derived preosteoblasts MC 3T3-E1. In CVCs, MM-LDL but not native LDL inhibited proliferation, ca used a dose-dependent increase in alkaline phosphatase activity, which is a marker of osteoblastic differentiation, and induced the formatio n of extensive areas of calcification. Similar to MM-LDL, oxidized toy l-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC) and the isop rostane 8-iso prostaglandin E-2 but not PAPC or isoprostane 8-iso pros taglandin F-2 alpha induced alkaline phosphatase activity and differen tiation of CVCs. In contrast, MM-LDL and the above oxidized lipids inh ibited differentiation of the MC3T3-E1 bone cells, as evidenced by the ir stimulatory effect on proliferation and their inhibitory effect on the induction of alkaline phosphatase and calcium uptake. These result s suggest that specific oxidized lipids may be the common factors unde rlying the pathogenesis of both atherosclerotic calcification and oste oporosis.