Role of the Cholesterol Biosynthetic Pathway in Osteoblastic Differentiation of Marrow Stromal Cells

Parhami, Farhad; Mody, Nilam; Gharavi, Nima M.; Ballard, Alex; Tintut, Yin; Demer, Linda L.

doi:10.1359/jbmr.2002.17.11.1997

Cited by 68 publications

(60 citation statements)

References 48 publications

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“…They promoted MSC differentiation to osteoblasts and inhibited adipogenic differentiation [32] . However, treatment of pluripotent mouse MSCs M2-10B4 with mevastatin or mevinolin inhibited the maturation of these cells into functional osteoblastic cells, and the effects of mevastatin were reversed by mevalonate [33] . The cholesterol biosynthetic pathway is needed for bone cell differentiation and maturation.…”

Section: Discussionmentioning

confidence: 96%

Osteogenic effects of D(+)β-3,4-dihydroxyphenyl lactic acid (salvianic acid A, SAA) on osteoblasts and bone marrow stromal cells of intact and prednisone-treated rats

Cui

Liu

et al. 2009

Acta Pharmacol Sin

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Aim:Previous studies have shown that D(+)β-3,4-dihydroxyphenyl lactic acid (salvianic acid A, SAA) has anabolic effects on prednisone (GC)-induced osteoporosis in rats. The current study aims to investigate the molecular mechanism of SAA's impact on osteogenesis and adipogenesis in bone marrow stromal cells in intact and GC-treated rats. Methods: For in vitro study, newborn rat calvaria osteoblasts (rOBs) and rat bone marrow stromal cells (rMSCs) were isolated, identified and cultured with SAA at different concentrations to evaluate SAA's influence on osteogenesis and adipogenesis. In addition, 3-month-old Sprague-Dawley (SD) male rats were treated with distilled water, prednisone alone (3.0 mg·kg -1 ·d -1 ) or prednisone (3.0 mg·kg -1 ·d -1 ) and SAA (25 mg·kg -1 ·d -1 ) for 45 d. At the end point, the different groups of rMSCs were isolated by density-gradient centrifugation and cultured. Results: (1) At 0.1-10.0 mg/L, SAA increased ALP activity, type I collagen (Coll-I) mRNA and OPG mRNA expression and stimulated nodule mineralization of rOBs. SAA (0.5 mg/L) also significantly increased the ALP activity of rMSCs without a need for osteogenesis-inducing medium. At 5.0 mg/L, SAA decreased the number of adipocytes with less lipid droplet formation from the rMSCs, which typically undergo adipocyte induction. (2) Coll-I expression was markedly decreased, whereas lipoprotein lipase (LPL) mRNA expression increased by 98% when compared with the first generation of rMSCs in GC-treated rats. The SAA-treated rats demonstrated an over 2-fold increase in Coll-I expression when compared with intact rats and further showed a significant decrease in LPL expression when compared with GC-treated rats. When rMSCs were co-cultured with SAA (0.5 mg/L) in vitro, SAA did not affect Coll-I and LPL gene expression in intact rats but significantly increased Coll-I and decreased LPL gene expression in GC-treated rats. Conclusion: SAA protected bone from GC-induced bone marrow impairment by stimulating osteogenesis and depressing adipogenesis in bone marrow stromal cells both in vivo and in vitro. The data indicated that aqueous extract of Salvia miltiorrhiza, which include SAA, may serve as an active anabolic agent and a useful therapeutic strategy for the treatment of GC-associated osteoporosis.

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Section: Discussionmentioning

confidence: 96%

Osteogenic effects of D(+)β-3,4-dihydroxyphenyl lactic acid (salvianic acid A, SAA) on osteoblasts and bone marrow stromal cells of intact and prednisone-treated rats

Cui

Liu

et al. 2009

Acta Pharmacol Sin

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“…Some found an association of hypercholesterolemia with lower BMD [5][6][7][8][9][10], and others with higher BMD [11], while yet others found no association at all [12,13]. On the other hand, both in vitro and in vivo animal model studies have demonstrated some detrimental effects of hypercholesterolemia or dyslipidemia on bone metabolism [14][15][16][17][18][19][20][21][22][23]. In in vitro studies, osteoblastic differentiation has been shown to be inhibited by atherogenic lipids [14,15].…”

mentioning

confidence: 99%

“…In in vitro studies, osteoblastic differentiation has been shown to be inhibited by atherogenic lipids [14,15]. The mevalonate pathway has recently been proposed as essential for not only the synthesis of cholesterol but also the regulation of bone cell proliferation or apoptosis [16,17,24]. In addition, LDL receptor-related protein 5 (LRP5) has recently been identified as a critical regulator of osteoblastic proliferation [18], and a mutation in LRP5 as causing significant reduction in BMD in both humans and mice [19,20].…”

mentioning

confidence: 99%

“…Clarifying bone metabolism in hypercholesterolemia will be helpful for ascertaining whether the above-mentioned potentially detrimental effects detected in in vitro or animal models [14][15][16][17][18][19][20][21][23][24][25] also exist in humans. In addition, such clarification should aid the search for an answer for the controversial findings of previous clinical studies [5][6][7][8][9][10][11][12][13] of the relationship between hypercholesterolemia and osteoporosis, and will promote our understanding of the underlying pathomechanisms, if any, for these two diseases.…”

mentioning

confidence: 99%

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Increased Bone Turnover in Patients with Hypercholesterolemia

et al. 2008

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Abstract. Osteoporosis has been linked with arteriosclerotic vascular diseases, suggesting that hypercholesterolemia or dyslipidemia may be a common pathogenetic factor underlying these diseases. However, little is known about the relationship between osteoporosis and hypercholesterolemia. The purpose of this study was, therefore, to investigate the effects of hypercholesterolemia upon bone metabolism, by measuring bone turnover markers in hypercholesterolemic patients. This study included 281 Japanese patients with hypercholesterolemia, and 267 control subjects. Serum bonespecific alkaline phosphatase (BAP) of the patients was significantly higher than that of the controls in women. Serum N-terminal telopeptide of type I collagen (NTx) of the patients was significantly higher than that of the controls in both men and women. In addition, both BAP and NTx in men showed a significantly negative correlation with high density lipoprotein cholesterol (HDL-C). On the other hand, in women, both BAP and NTx showed a significantly positive correlation with total cholesterol and low density lipoprotein cholesterol (LDL-C). These results indicate increased bone turnover in hypercholesterolemic or dyslipidemic patients regardless of gender, and suggest the importance of treating hypercholesterolemia or dyslipidemia in order to prevent not only arteriosclerotic complications but also osteoporotic bone loss and subsequent fractures.

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“…Previous study reported that postmenopausal women with hypercholesterolemia had about 10% lower BMD of various skeletal sites than those with normal lipid levels (Orozco, 2004). This observation could be explained by that totalcholesterol and its metabolites played an important role for osteoblast differentiation and activities (Parhami et al, 2000(Parhami et al, , 2002. We previously reported that intake of cowpea significantly increased bone formation markers and decreased bone resorption markers (Lee et al, 2011) Effect of cowpea on lipid profile has been reported previously.…”

Section: Discussionmentioning

confidence: 78%

Effects of Legumes Consumption on the Association of Cholesterol and Bone Mineral Density in Ovariectomized Rats

Kim¹,

Jin²,

Park³

2012

Korean Journal of Medicinal Crop Science

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: Soy isoflavones have been suggested to improve bone loss and lipid profile in postmenopausal women and ovariectomized rats. In present study, we investigated the hypothesis that consumption of soybean, mung bean, cowpea and azuki bean has a beneficial effect on lipid profile which associates with bone mass in ovariectomized rats. Forty two female Sprague-Dawley rats were either sham-operated (Sham) or surgically ovariectomized (OVX). Sham and OVX groups were fed a regular AIN-93M diet, but ovariectomized rats with soybean (OS), mung bean (OM), cowpea (OC) or adzuki bean (OA) were fed AIN-93M diet replacing 35% of corn starch with powdered OS, OM, OC or OA for 10 weeks. Total-and LDL-cholesterol concentrations were significantly lower in Sham and OC groups than other OVX groups. There was significant negative association between total cholesterol concentration and bone mineral density (BMD) of tibia in only OC group. In conclusion, total-cholesterol concentration was significantly and negatively correlated with BMD in rats consumed cowpea, suggesting that the reduced cholesterol concentration may have a beneficial effect on bone mass.

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Role of the Cholesterol Biosynthetic Pathway in Osteoblastic Differentiation of Marrow Stromal Cells

Cited by 68 publications

References 48 publications

Osteogenic effects of D(+)β-3,4-dihydroxyphenyl lactic acid (salvianic acid A, SAA) on osteoblasts and bone marrow stromal cells of intact and prednisone-treated rats

Osteogenic effects of D(+)β-3,4-dihydroxyphenyl lactic acid (salvianic acid A, SAA) on osteoblasts and bone marrow stromal cells of intact and prednisone-treated rats

Increased Bone Turnover in Patients with Hypercholesterolemia

Effects of Legumes Consumption on the Association of Cholesterol and Bone Mineral Density in Ovariectomized Rats

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