Abstract Atherosclerotic calcification and osteoporosis often coexist in patients, yielding formation of bone mineral vascular walls its simultaneous loss from bone. To assess the potential role lipoproteins both processes, we examined effects minimally oxidized low-density lipoprotein (MM-LDL) several other lipid oxidation products on calcifying cells (CVCs) bone-derived preosteoblasts MC3T3-E1. In CVCs, MM-LDL but not native LDL inhibited proliferation, caused a dose-dependent increase...

Background —Vascular calcification is an ectopic that commonly occurs in atherosclerosis. Because tumor necrosis factor-α (TNF-α), a pleiotropic cytokine found atherosclerotic lesions, also regulator of bone formation, we investigated the role TNF-α vitro vascular calcification. Methods and Results —A cloned subpopulation bovine aortic smooth muscle cells previously shown capable osteoblastic differentiation was treated with TNF-α, mineralization were assessed. Treatment for 3 days induced...

Background— In diabetes or atherosclerosis, ectopic bone, fat, cartilage, and marrow often develop in arteries. However the mechanism is unknown. We have previously identified a subpopulation of vascular cells (calcifying cells, CVC), derived by dilutional cloning bovine aortic medial showed that they undergo osteoblastic differentiation mineralization. now show CVC potential to differentiate along other mesenchymal lineages. Methods Results— To determine multilineage CVC, molecular...

Calcification is a common complication of atherosclerosis and other chronic inflammatory processes that involves infiltration monocytes accumulation macrophages.To determine whether these cells modulate vascular calcification in vitro, calcifying (CVCs), subpopulation osteoblast-like derived from the artery wall, were cocultured with human peripheral blood for 5 days. Results showed alkaline phosphatase (ALP) activity, marker osteoblastic differentiation, was significantly greater cocultures...

Abstract —Leptin, the product of ob gene, regulates food intake, energy expenditure, and other physiological functions peripheral tissues. Leptin receptors have been identified in hypothalamus extrahypothalamic Increased circulating leptin levels correlated with cardiovascular disease, obesity, aging, infection bacterial lipopolysaccharide, high-fat diets. All these conditions also increased vascular calcification, a hallmark atherosclerotic age-related disease. In addition, differentiation...

Abstract The epidemiological correlation between osteoporosis and cardiovascular disease is independent of age, but the basis for this unknown. We previously found that atherogenic oxidized lipids inhibit osteoblastic differentiation in vitro ex vivo, suggesting an diet may contribute to both diseases. In study, effects high-fat versus control chow on bone were tested two strains mice with genetically different susceptibility atherosclerosis lipid oxidation. After 4 months 7 diets, mineral...

In osteoporosis, the bone marrow stroma osteogenic cell population declines and adipocyte numbers increase. We recently showed that oxidized lipids inhibit differentiation of preosteoblasts. this report, we assess effect minimally low density lipoprotein (MM-LDL) on osteoblastic murine stromal cells, M2-10B4. MM-LDL, but not native LDL, inhibited as demonstrated by inhibition alkaline phosphatase activity, collagen I processing, mineralization, through a mitogen-activated protein...

Background— The role of osteoprotegerin in vascular disease is unclear. Recent observational studies show that serum levels are associated with the severity and progression coronary artery disease, atherosclerosis, calcification patients. However, genetic treatment mice suggest may protect against calcification. Methods Results— To test whether induces or prevents we treated atherogenic diet–fed ldlr (−/−) recombinant (Fc-OPG) vehicle for 5 months. Vehicle-treated developed significant,...

Accumulating evidence has suggested the protective role of HDL in cardiovascular disease processes. Calcification is a common feature atherosclerotic lesions and contributes to complications due loss aortic resilience function. Recent studies have that vascular calcification shares several features with skeletal bone formation at cellular molecular levels. These include presence osteoblast-like calcifying cells artery wall undergo osteoblastic differentiation vitro. We hypothesized may also...

Objectives— Osteoporosis is associated epidemiologically with atherosclerosis and hyperlipidemia. We previously found that atherogenic lipids regulate bone formation. To determine whether hyperlipidemia also affects resorption, we compared osteoclastogenesis in marrow preosteoclasts derived from hyperlipidemic versus control mice. Methods— Nonadherent cells low-density lipoprotein receptor−/− (LDLR−/−)and C57BL/6J mice were cultured M-CSF ligand for receptor activator of nuclear...

Objective— Clinical and experimental studies demonstrate the important roles of vascular smooth muscle cells (VSMC) in pathogenesis atherosclerosis. We have previously determined that osteogenic transcription factor Runx2 is essential for VSMC calcification. The present study characterized Runx2-regulated signals their potential Methods Results— In vivo with atherogenic apolipoprotein E −/− mice demonstrated increased oxidative stress was associated upregulation receptor activator nuclear κB...

Abstract Hyperlipidemia increases the risk for generation of lipid oxidation products, which accumulate in subendothelial spaces vasculature and bone. Atherogenic high-fat diets increase serum levels oxidized lipids, are known to attenuate osteogenesis culture promote bone loss mice. In this study, we investigated whether lipids affect regeneration mechanical strength. Wild-type (WT) hyperlipidemic (Ldlr−/−) mice were placed on a (HF) diet 13 weeks. Bilateral cranial defects introduced each...

Left-right (LR) asymmetry is ubiquitous in animal development. Cytoskeletal chirality was recently reported to specify LR embryogenesis, suggesting that tissue morphogenesis coordinated by single- or multi-cell organizers. Thus, organize at multiscale levels of morphogenesis, cells with must also be present adequate numbers. However, observation rarely cultured cells.

Research in the area of vascular calcification has grown rapidly past decade, and there is a greater understanding its active regulatory mechanisms. This brief review covers ideas presented 2003 Jeffrey M. Hoeg Award lecture, including concepts that bone tissue forms artery wall patients with atherosclerosis, cells undergo osteoblastic differentiation, morphogenetic protein matrix GLA regulate opposition, inflammatory cytokines lipids promote cell but inhibit these same factors...

In embryogenesis, immature mesenchymal cells aggregate and organize into patterned tissues. Later in life, a pathological recapitulation of this process takes place atherosclerotic lesions, when vascular trabecular bone tissue within the artery wall. Here we show that multipotential adult self-organize vitro patterns are predicted by mathematical model based on molecular morphogens interacting reaction-diffusion process. We identify activator inhibitor for stripe, spot, labyrinthine confirm...

The cAMP pathway, a major intracellular pathway mediating parathyroid hormone signal, regulates osteoblastic function. Parathyroid (through activation of protein kinase A) has also been shown to stimulate ubiquitin/proteasome activity in osteoblasts. Since the osteoblast-specific transcription factor Osf2/Cbfa1 is important for differentiation cells, we examined roles and pathways regulation Cbfa1. In cell line, MC3T3-E1, continuous treatment with elevating agents inhibited both based on...

Lipid oxidation products promote atherosclerosis and may also affect osteoporosis. We showed previously that oxidized lipids including 8-isoprostaglandin E2 (isoPGE2) inhibit osteoblastic differentiation of preosteoblasts. Since osteoporosis is mediated both by decreased bone formation increased osteoclastic resorption, we assessed whether regulate the potential marrow hematopoietic cells. Treatment marrow-derived preosteoclasts with isoPGE2 enhanced as evidenced tartrate-resistant acid...