AIMTo study the effect of propylene glycol mannate sulfate (PGMS) on blood lipids and lipoprotein lipase in hyperlipidemic rat, and its anti-hyperlipidemic mechanism.

METHODSPGMS was administered ig at different doses (37.8 mg.kg-1.d-1 and 75.6 mg.kg-1.d-1) to hyperlipidemic rats for three weeks and blood serum was obtained after starved 12 h. Total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were examined. The mRNA expression of lipoprotein lipase (LPL) in liver, spleen and artery was detected by reverse transcription polymerase chain reaction (RT-PCR).

RESULTSPGMS significantly decreased the levels of TC, TG and LDL-C and increased that of HDL-C in hyperlipidemic serum dose-dependently. PGMS was shown to increase the level of LPL mRNA expression, which is related directly to the controlling effects of PGMS on blood lipids.

CONCLUSIONPGMS modulated blood lipids by promoting mRNA expression of LPL. This may be one important mechanism of PGMS to modulate blood lipids.

Animals ; Cholesterol, HDL ; blood ; Disease Models, Animal ; Hyperlipidemias ; blood ; drug therapy ; enzymology ; Lipoprotein Lipase ; biosynthesis ; genetics ; Male ; Propylene Glycols ; therapeutic use ; RNA, Messenger ; biosynthesis ; Random Allocation ; Rats ; Rats, Wistar ; Triglycerides ; blood

OBJECTIVETo measure the osteogenesis and adipogenesis potentiality of rat marrow stromal cells (MSCs) derived from 3, 6, 9, 12-month-old doner rats.

METHODSRat MSCs were induced to osteoblast or adipocyte by osteogenic inducer or adipogenic inducer. In different times, 3 and 12-month-old rat MSCs were observed by histochemistry staining; the mRNA level of type I collagen and lipoprotein lipase of 3, 6, 9, 12-month-old rat MSCs were measured by RT-PCR.

RESULTSThe expression of alkaline phosphatase (ALP) of the control group and induced group of 12-month old rat MSCs was less than that of 3-month old rat MSCs after 1-week osteogenic induction. 12 days later, calcification was observed in 3-month old group. Lipid droplets occurred in the cells of 12-month old group after 2-day adipogenic induction, while these droplets occurred after 3-day or 4-day induction in 3-month old group. The mRNA level of type I collagen decreased with the increase of age. The mRNA level of lipoprotein lipase of younger rats was lower than that of older rats. Both of the changes were more significantly with the increase of the induction time.

CONCLUSIONSWith the increase of age, the ability of osteogenesis of rat MSCs decreased, but the ability of adipogenesis increased.

Adipose Tissue ; growth & development ; Aging ; Alkaline Phosphatase ; metabolism ; Animals ; Base Sequence ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Cells, Cultured ; Collagen Type I ; biosynthesis ; genetics ; Female ; Lipoprotein Lipase ; biosynthesis ; genetics ; Molecular Sequence Data ; Osteogenesis ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley ; Stromal Cells ; cytology

Parathyroid hormone-related protein (PTHrP) is synthesized by diverse tissues, and its processing produces several fragments, each with apparently distinct autocrine and paracrine bioactivities. In bone, PTHrP appears to modulate bone formation in part through promoting osteoblast differentiation. The putative effect of PTH-like and PTH-unrelated fragments of PTHrP on human mesenchymal stem cell (MSCs) is not well known. Human MSCs were treated with PTHrP (1-36) or PTHrP (107-139) or both (each at 10 nM) in osteogenic or adipogenic medium, from the start or after 6 days of exposure to the corresponding medium, and the expression of several osteoblastogenic and adipogenic markers was analyzed. PTHrP (1-36) inhibited adipogenesis in MSCs and favoured the expression of osteogenic early markers. The opposite was observed with treatment of MSCs with PTHrP (107-139). Moreover, inhibition of the adipogenic differentiation by PTHrP (1-36) prevailed in the presence of PTHrP (107-139). The PTH/PTHrP type 1 receptor (PTH1R) gene expression was maximum in the earlier and later stages of osteogenesis and adipogenesis, respectively. While PTHrP (107-139) did not modify the PTH1R overexpression during adipogenesis, PTHrP (1-36) did inhibit it; an effect which was partially affected by PTHrP (7-34), a PTH1R antagonist, at 1 microM. These findings demonstrate that both PTHrP domains can exert varying effects on human MSCs differentiation. PTHrP (107-139) showed a tendency to favor adipogenesis, while PTHrP (1-36) induced a mild osteogenic effect in these cells, and inhibited their adipocytic commitment. This further supports the potential anabolic action of the latter peptide in humans.
Adipogenesis/drug effects ; Alkaline Phosphatase/biosynthesis/genetics ; Antigens, Differentiation/biosynthesis/genetics ; Bone Marrow/pathology ; Cell Differentiation/drug effects ; Cells, Cultured ; Core Binding Factor Alpha 1 Subunit/biosynthesis/genetics ; Culture Media ; Gene Expression Regulation ; Humans ; Lipoprotein Lipase/biosynthesis/genetics ; Mesenchymal Stem Cells/*drug effects/metabolism/pathology ; Osteoblasts/drug effects/*metabolism/pathology ; Osteogenesis/drug effects ; PPAR gamma/biosynthesis/genetics ; Parathyroid Hormone/*pharmacology ; Peptide Fragments/*pharmacology ; Receptor, Parathyroid Hormone, Type 1/antagonists & inhibitors