title: Sirt1 is involved in decreased bone formation in aged apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Geriatrics, Huadong Hospital, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China.|Department of Bone Metabolism, Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai 200040, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hong
authors.affiliation: Department of Bone Metabolism, Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Xiao-ya
authors.initials: XY
authors.lastname: Xu
authors.affiliation: Department of Geriatrics, Huadong Hospital, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China.
authors.forename: Zhao-hui
authors.initials: ZH
authors.lastname: Qiu
authors.affiliation: Department of Bone Metabolism, Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Jian-jun
authors.initials: JJ
authors.lastname: Gao
authors.affiliation: Department of Osteoporosis and Related Bone Disease, Shanghai 6th People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China.
authors.forename: Zhan-ying
authors.initials: ZY
authors.lastname: Wei
authors.affiliation: Laboratory Animal Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhen
authors.affiliation: Department of Nephrology, Huadong Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Huadong Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Zhi-bing
authors.initials: ZB
authors.lastname: Ye
mesh_terms: D000375:Aging; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D015519:Bone Density; D002478:Cells, Cultured; D015536:Down-Regulation; D017353:Gene Deletion; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis; D056564:Sirtuin 1 / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1