Leptin promotes osteoblast differentiation and mineralization of primary cultures of vascular smooth muscle cells by inhibiting glycogen synthase kinase (GSK)-3β.

In this study, we begin to investigate the underlying mechanism of leptin-induced vascular calcification. We found that treatment of cultured bovine aortic smooth muscle cells (BASMCs) with leptin (0.5-4 μg/ml) induced osteoblast differentiation in a dose-dependent manner.

Oxidized low-density lipoprotein promotes osteoblast differentiation in primary cultures of vascular smooth muscle cells by up-regulating Osterix expression in an Msx2-dependent manner.

We have previously shown that oxidized low-density lipoproteins (oxLDLs) act synergistically with β-glycerophosphate to induce the osteogenic differentiation of primary bovine aortic smooth muscle cells (BASMCs). In the present study, we attempt to resolve the mechanism responsible for this effect by examining the expression of several osteoblast-specific transcription factors. Thus, by culturing BASMCs in the absence or presence of β-glycerophosphate and/or oxLDL, we demonstrate that β-glycerophosphate induces both Runx2 and Osterix (Osx) expression.

Effect of leptin on vascular calcification in apolipoprotein E-deficient mice.

Objective: The adipocytokine leptin has been proposed to increase cardiovascular risk in both obese and diabetic individuals. In the current study, therefore, we used apoE-deficient mice to examine the effects of leptin on both lesion size and calcification.

Methods And Results: Mice were treated with once daily intraperitoneal injections of leptin (125 microg/mouse/d) for 2 months.

Conjugated linoleic acid prevents growth attenuation induced by corticosteroid administration and increases bone mineral content in young rats.

Corticosteroids are a common therapy in many disease states, despite frequent and potentially serious side effects. Nutritional supplementation with conjugated linoleic acid (CLA) has been shown to increase fat-free mass, whereas supplementation with n-3 and n-6 fatty acids has been shown to increase bone mineral density (BMD). To determine whether CLA can attenuate the side effects of 8 weeks of corticosteroid administration, we randomized twenty-four 5-week-old male Sprague-Dawley rats into 1 of 4 groups: control; control + methylprednisolone (7 mg.

Inhibition of osteolytic bone metastasis by unfractionated heparin.

In the current study, we examine heparin's anti-metastatic properties by using a well-defined mouse model of osteolytic bone metastasis. C57BL/6 mice were treated with increasing doses of unfractionated heparin (15, 20, or 25 units/mouse) 30 min prior to the left ventricular injection of GFP-transfected B16F10 melanoma cells. Heparin's effect on tumour burden and bone strength was then quantified 14 days later by bone histomorphometry and biomechanical testing, respectively.

Oxidized low-density lipoprotein acts synergistically with beta-glycerophosphate to induce osteoblast differentiation in primary cultures of vascular smooth muscle cells.

Previous studies have localized osteoblast specific markers to sites of calcified atherosclerotic lesions. We therefore decided to use an established in vitro model of vascular calcification in order to confirm earlier reports of oxidized low-density lipoprotein (oxLDL) promoting the osteogenic differentiation of vascular smooth muscle cells. Treatment of primary bovine aortic smooth muscle cells (BASMCs) with beta-glycerophosphate was found to induce a time-dependent increase in osteoblast differentiation.

The effects of heparin and low molecular weight heparins on bone.

Recent clinical trials have shown that the risk of developing osteoporosis is substantially lower when low molecular weight heparins (LMWHs) are used in place of unfractionated heparin. While the reason(s) for this difference has not been fully elucidated, studies with animals have suggested that heparin causes bone loss by both decreasing bone formation and increasing bone resorption. In contrast, LMWHs appear to cause less bone loss because they only decrease bone formation.

Creatine monohydrate increases bone mineral density in young Sprague-Dawley rats.

Introduction: Creatine kinase, found in osteoblasts, is an enzyme that is upregulated in response to interventions that enhance bone mass accretion. Creatine monohydrate supplementation can increase fat-free mass in young healthy men and women and can reduce markers of bone breakdown in boys with Duchenne muscular dystrophy.

Purpose: The objective of this study was to determine the influence of supplementation with creatine monohydrate on bone structure and function in growing rats, to establish a therapeutic model.

Heparin synergistically enhances interleukin-11 signaling through up-regulation of the MAPK pathway.

Using an animal model of heparin-induced osteoporosis we previously demonstrated that heparin causes bone loss, in part, by increasing osteoclast number and activity. Furthermore, we found that, although heparin alone has no effect, it is able to synergistically enhance Interleukin-11 (IL-11)-induced signal transducer and activator of transcription 3 (STAT3) activation and thus increase osteoclast formation in vitro. In the present study, we examine the effect of various serine kinase inhibitors on the ability of heparin to act synergistically with IL-11.

The effect of heparin on osteoblast differentiation and activity in primary cultures of bovine aortic smooth muscle cells.

Recent studies have suggested that aortic smooth muscle cells undergo a phenotypic transition into osteoblast-like cells and mineralize when cultured in the presence of beta-glycerophosphate. Since we had previously demonstrated that heparin could inhibit osteoblast differentiation and mineralization in primary cultures of murine calvaria cells, we were interested in determining if heparin would have a similar effect when primary aortic smooth muscle cells were cultured in the presence of beta-glycerophosphate. The effect of heparin and low molecular weight heparin (LMWH) on osteoblast differentiation and activity was therefore examined in primary cultures of bovine aortic smooth muscle cells (BASMC) over a 14-day period.

Differential effects of heparin and low molecular weight heparin on osteoblastogenesis and adipogenesis in vitro.

We have previously demonstrated that heparin produces cancellous bone loss in rats due in part to a decrease in the number of osteoblasts lining the trabecular bone surface. In the present study, we use a stromal-derived cell culture system together with measurements of alkaline phosphatase (ALP) activity, to compare the effects of heparin and the low molecular weight heparin (LMWH), Fragmin, on osteoblast differentiation in vitro. In addition, we examined the possibility that both heparin and LMWH can induce adipogenesis in our stromal cell culture system.

Localization of heparin and low-molecular-weight heparin in the rat kidney.

Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are cleared, at least in part, by the kidneys through a poorly understood process. This study was undertaken to explore the mechanism of renal clearance of these drugs. Rats were given fluorescein-5-isothiocyanate (FITC)-labeled UFH or LMWH intravenously.

Neutralization of interleukin-11 activity decreases osteoclast formation and increases cancellous bone volume in ovariectomized mice.

The issue of whether interleukin-11 (IL-11) contributes to bone loss during states of estrogen deficiency has not been previously determined. We therefore randomized ovariectomized (OVX) mice to once daily interperitoneal injections of either sheep anti-murine IL-11 Ab or normal sheep IgG (NSIgG) for 21 days, and then determined the effects on bone using bone histomorphometry. Here we report that treatment of OVX mice with anti-IL-11 Ab significantly increases both trabecular width and cancellous bone volume.

Heparin acts synergistically with interleukin-11 to induce STAT3 activation and in vitro osteoclast formation.

We have previously demonstrated that long-term heparin treatment causes cancellous bone loss in rats due in part to an increase in the number of osteoclasts lining the trabecular bone surface. In the present study, we investigated this phenomenon by examining the ability of heparin to synergistically enhance interleukin-11 (IL-11)-induced osteoclast formation. Treatment of murine calvaria and bone marrow cells with IL-11 was found to induce the formation of tartrate-resistant acid phosphatase-positive (TRAP(+)) multinucleated cells (MNCs) in a dose-dependent fashion.

Long-term treatment with sodium warfarin results in decreased femoral bone strength and cancellous bone volume in rats.

The issue of whether long-term sodium warfarin therapy results in decreased bone density is controversial. To address this question, we randomized rats to once daily subcutaneous injections of either sodium warfarin (0.20 or 0.