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Sirt1 is involved in decreased bone formation in aged apolipoprotein E-deficient mice.

Hong W, Xu XY, Qiu ZH, Gao JJ, Wei ZY, Zhen L, Zhang XL, Ye ZB - Acta Pharmacol. Sin. (2015)

Bottom Line: In contrast, aged apoE(-/-) mice showed reduced bone formation and lower bone mass relative to age-matched WT mice, accompanied by lower serum OCN levels, and markedly reduced expression levels of Sirt1, Runx2, ALP and OCN in bone tissue.After BMSCs were exposed to ox-LDL (20 μg/mL), the expression of Sirt1 and Runx2 proteins was significantly increased at 12 h, and then decreased at 72 h.Treatment with the Sirt1 inhibitor EX527 (10 μmol/L) suppressed the expression of Runx2, ALP and OCN in BMSCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Geriatrics, Huadong Hospital, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China.

ABSTRACT

Aim: Apolipoprotein E (ApoE) plays an important role in the transport and metabolism of lipids. Recent studies show that bone mass is increased in young apoE(-/-) mice. In this study we investigated the bone phenotype and metabolism in aged apoE(-/-) mice.

Methods: Femurs and tibias were collected from 18- and 72-week-old apoE(-/-) mice and their age-matched wild-type (WT) littermates, and examined using micro-CT and histological analysis. Serum levels of total cholesterol, oxidized low-density lipoprotein (ox-LDL) and bone turnover markers were measured. Cultured bone mesenchymal stem cells (BMSCs) from tibias and femurs of 18-week-old apoE(-/-) mice were used in experiments in vitro. The expression levels of Sirt1 and Runx2 in bone tissue and BMSCs were measured using RT-PCR and Western blot analysis.

Results: Compared with age-matched WT littermates, young apoE(-/-) mice exhibited high bone mass with increased bone formation, accompanied by higher serum levels of bone turnover markers OCN and TRAP5b, and higher expression levels of Sirt1, Runx2, ALP and OCN in bone tissue. In contrast, aged apoE(-/-) mice showed reduced bone formation and lower bone mass relative to age-matched WT mice, accompanied by lower serum OCN levels, and markedly reduced expression levels of Sirt1, Runx2, ALP and OCN in bone tissue. After BMSCs were exposed to ox-LDL (20 μg/mL), the expression of Sirt1 and Runx2 proteins was significantly increased at 12 h, and then decreased at 72 h. Treatment with the Sirt1 inhibitor EX527 (10 μmol/L) suppressed the expression of Runx2, ALP and OCN in BMSCs.

Conclusion: In contrast to young apoE(-/-) mice, aged apoE(-/-) mice showe lower bone mass than age-matched WT mice. Long-lasting exposure to ox-LDL decreases the expression of Sirt1 and Runx2 in BMSCs, which may explain the decreased bone formation in aged apoE(-/-) mice.

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Related in: MedlinePlus

Sirt1 induced bone formation in the bone mesenchymal stem cells (BMSCs) fromapoE−/− mice in vitro. BMSCsfrom 18-week-old apoE−/− mice were culturedwith 10 μmol/L EX-527 and the relative mRNA expression of Sirt1,Runx2, ALP and OCN (A) and protein (Western blotting) expression of Sirt1and Runx2 (B) were analyzed for the mean change relative to an untreatedcontrol. Mean±SD, n=4.bP<0.05, cP<0.01vs control.
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fig5: Sirt1 induced bone formation in the bone mesenchymal stem cells (BMSCs) fromapoE−/− mice in vitro. BMSCsfrom 18-week-old apoE−/− mice were culturedwith 10 μmol/L EX-527 and the relative mRNA expression of Sirt1,Runx2, ALP and OCN (A) and protein (Western blotting) expression of Sirt1and Runx2 (B) were analyzed for the mean change relative to an untreatedcontrol. Mean±SD, n=4.bP<0.05, cP<0.01vs control.

Mentions: To further investigate whether Sirt1 plays an active role in thedifferentiation of BMSCs, we treated BMSCs from 18-week-oldapoE−/− mice with the Sirt1 inhibitorEX527. After treatment with EX527 (10 μmol/L), the mRNA (Figure 5A) and protein levels (Figure 5B) of Runx2 decreased significantly(−23.57%, P<0.05 and −54.38%,P<0.01, respectively).


Sirt1 is involved in decreased bone formation in aged apolipoprotein E-deficient mice.

Hong W, Xu XY, Qiu ZH, Gao JJ, Wei ZY, Zhen L, Zhang XL, Ye ZB - Acta Pharmacol. Sin. (2015)

Sirt1 induced bone formation in the bone mesenchymal stem cells (BMSCs) fromapoE−/− mice in vitro. BMSCsfrom 18-week-old apoE−/− mice were culturedwith 10 μmol/L EX-527 and the relative mRNA expression of Sirt1,Runx2, ALP and OCN (A) and protein (Western blotting) expression of Sirt1and Runx2 (B) were analyzed for the mean change relative to an untreatedcontrol. Mean±SD, n=4.bP<0.05, cP<0.01vs control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4816239&req=5

fig5: Sirt1 induced bone formation in the bone mesenchymal stem cells (BMSCs) fromapoE−/− mice in vitro. BMSCsfrom 18-week-old apoE−/− mice were culturedwith 10 μmol/L EX-527 and the relative mRNA expression of Sirt1,Runx2, ALP and OCN (A) and protein (Western blotting) expression of Sirt1and Runx2 (B) were analyzed for the mean change relative to an untreatedcontrol. Mean±SD, n=4.bP<0.05, cP<0.01vs control.
Mentions: To further investigate whether Sirt1 plays an active role in thedifferentiation of BMSCs, we treated BMSCs from 18-week-oldapoE−/− mice with the Sirt1 inhibitorEX527. After treatment with EX527 (10 μmol/L), the mRNA (Figure 5A) and protein levels (Figure 5B) of Runx2 decreased significantly(−23.57%, P<0.05 and −54.38%,P<0.01, respectively).

Bottom Line: In contrast, aged apoE(-/-) mice showed reduced bone formation and lower bone mass relative to age-matched WT mice, accompanied by lower serum OCN levels, and markedly reduced expression levels of Sirt1, Runx2, ALP and OCN in bone tissue.After BMSCs were exposed to ox-LDL (20 μg/mL), the expression of Sirt1 and Runx2 proteins was significantly increased at 12 h, and then decreased at 72 h.Treatment with the Sirt1 inhibitor EX527 (10 μmol/L) suppressed the expression of Runx2, ALP and OCN in BMSCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Geriatrics, Huadong Hospital, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China.

ABSTRACT

Aim: Apolipoprotein E (ApoE) plays an important role in the transport and metabolism of lipids. Recent studies show that bone mass is increased in young apoE(-/-) mice. In this study we investigated the bone phenotype and metabolism in aged apoE(-/-) mice.

Methods: Femurs and tibias were collected from 18- and 72-week-old apoE(-/-) mice and their age-matched wild-type (WT) littermates, and examined using micro-CT and histological analysis. Serum levels of total cholesterol, oxidized low-density lipoprotein (ox-LDL) and bone turnover markers were measured. Cultured bone mesenchymal stem cells (BMSCs) from tibias and femurs of 18-week-old apoE(-/-) mice were used in experiments in vitro. The expression levels of Sirt1 and Runx2 in bone tissue and BMSCs were measured using RT-PCR and Western blot analysis.

Results: Compared with age-matched WT littermates, young apoE(-/-) mice exhibited high bone mass with increased bone formation, accompanied by higher serum levels of bone turnover markers OCN and TRAP5b, and higher expression levels of Sirt1, Runx2, ALP and OCN in bone tissue. In contrast, aged apoE(-/-) mice showed reduced bone formation and lower bone mass relative to age-matched WT mice, accompanied by lower serum OCN levels, and markedly reduced expression levels of Sirt1, Runx2, ALP and OCN in bone tissue. After BMSCs were exposed to ox-LDL (20 μg/mL), the expression of Sirt1 and Runx2 proteins was significantly increased at 12 h, and then decreased at 72 h. Treatment with the Sirt1 inhibitor EX527 (10 μmol/L) suppressed the expression of Runx2, ALP and OCN in BMSCs.

Conclusion: In contrast to young apoE(-/-) mice, aged apoE(-/-) mice showe lower bone mass than age-matched WT mice. Long-lasting exposure to ox-LDL decreases the expression of Sirt1 and Runx2 in BMSCs, which may explain the decreased bone formation in aged apoE(-/-) mice.

Show MeSH
Related in: MedlinePlus