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

Hong, Wei; Xu, Xiang; Qiu, Zhaohui; Gao, Jianjun; Wei, Zhanying; Li, Zhen; Zhang, Xiaoli; Ye, Zhi-bing

doi:10.1038/aps.2015.95

Cited by 16 publications

(22 citation statements)

References 52 publications

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“…Cellular lipoprotein uptake is dependent on the interaction of their protein moieties, such as apolipoprotein E (ApoE), a 34 kDa glycoprotein, which plays a central role in lipoprotein metabolism, with endocytotic cell surface lipoprotein receptors. Over the last few decades, numerous studies have confirmed apoE regulated bone metabolism in mice (10)(11)(12)(13), but the mechanism is still undefined. One possible molecular explanation was provided by a series of experiments that characterized the role of apoE in the uptake of triglyceride-rich lipoproteins (TRL) and TRL-associated vitamin K into osteoblasts (10).…”

Section: Introductionmentioning

confidence: 99%

Multifarious effects of 17-β-estradiol on apolipoprotein E receptors gene expression during osteoblast differentiation <i>in vitro </i>

Gui

Duan

Tang

et al. 2016

BST

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Section: Introductionmentioning

confidence: 99%

Multifarious effects of 17-β-estradiol on apolipoprotein E receptors gene expression during osteoblast differentiation <i>in vitro </i>

Gui

Duan

Tang

et al. 2016

BST

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“…This may have contributed to the bone loss in the aged apoE −/− mice seen in our previous study [29]. Statins have been proven to have a preventive effect on ageing through intervention with Sirt1 [49].…”

Section: Discussionmentioning

confidence: 61%

“…All samples were collected, and the Western blot was conducted as previously described [29]. The primary antibodies used were rabbit anti-Sirt1 (Cat.No:13161-1-AP;1:2000; Proteintech, Rosemont,USA), mouse anti-Runx2 (Cat.No:ab54868;1:1000; Abcam, CA, USA), and mouse anti-GAPDH (Cat.No:KC-5G4;1:10,000;…”

Section: Western Blot Analysismentioning

confidence: 99%

Atorvastatin Promotes Bone Formation in Aged apoE–/– Mice through the Sirt1–Runx2 Axis

Hong

Wei

Qiu

et al. 2020

Preprint

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Abstract Background Statins are the most widely used drugs in elderly patients, the most common clinical application of statins is in aged hyperlipemia patients. There are few studies on the effects and mechanisms of statins on bone in elderly mice with hyperlipemia. The study is to examine the effects of atorvastatin on bone phenotypes and metabolism in aged apolipoprotein E-deficient (apoE –/– ) mice, and the possible mechanisms involved in these changes. Methods Twenty-four 60-week-old apoE –/– mice were randomly allocated to two groups. Twelve mice were orally gavaged with atorvastatin (10 mg/kg body weight/day) for 12 weeks; the others served as the control group. Bone mass and skeletal microarchitecture were determined using micro-CT. Bone metabolism was assessed by serum analyses, qRT-PCR, and Western blot. Bone marrow-derived mesenchymal stem cells (BMSCs) from apoE –/– mice were differentiated into osteoblasts and treated with atorvastatin and Sirt1 inhibitor EX-527. Results The results showed that long-term administration of atorvastatin increases bone mass and improves bone microarchitecture in trabecular bone but not in cortical bone. Furthermore, the serum bone formation marker osteocalcin (OCN) was ameliorated by atorvastatin, whereas the bone resorption marker tartrate-resistant acid phosphatase 5b (Trap5b) did not appear to be impacted by atorvastatin treatment. The mRNA expression of Sirt1, runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and OCN in bone tissue were increased after atorvastatin administration. Western blot showed same trend in Sirt1 and Runx2. The in vitro study showed that when BMSCs from apoE –/– mice were pretreated with EX527, the higher expression of Runx2, ALP and OCN activated by atorvastatin decreased significantly or showed no difference compared with the control. The protein expression of Runx2 showed same trend. Conclusions Accordingly, the current study validates the hypothesis that atorvastatin can increase bone mass and promote osteogenesis in aged apoE −/− mice by regulating the Sirt1–Runx2 axis.

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“…Therefore, the stimulation of the BMP–Smad1/5/8–Runx2 signalling axis promotes osteogenic differentiation and bone remodelling in age‐related diseases (Chen et al., ). Previous studies suggest that SIRT1 and 6 promote osteogenic differentiation and bone formation via modulating the BMP signalling pathway in mesenchymal stem cells (Chen et al., ; Hong et al., ; Zhang et al., ). Our data also indicate that the expression of SIRT1 and 6 was significantly increased by IR and CR in RANKL‐treated BMMs.…”

Section: Discussionmentioning

confidence: 98%

Interval running training improves age‐related skeletal muscle wasting and bone loss: Experiments with ovariectomized rats

Kim

Jeon

et al. 2019

Experimental Physiology

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New Findings What is the central question of this study?What is the effect and mechanism of interval running training on age‐related muscle wasting and bone loss in an ovariectomized rat model? What is the main finding and its importance?Interval running training improved muscle growth and osteogenic differentiation by enhancing the expression of bone morphogenic proteins and sirtuins in ageing‐induced ovariectomized rats. Therefore, the repetition of low and high intensities within a single exercise bout, such as interval running training, may be recommended as a practical intervention to prevent skeletal muscle wasting and bone loss in the elderly. Abstract Effective prophylactic strategies are needed for the suppression of age‐related muscle wasting and bone loss after menopause. Exercise training is attractive due to its potential for improving energy metabolism, as well as age‐related muscle wasting and bone loss. In particular, interval running (IR) training involves a repetition of low and high intensities within a single exercise bout. Therefore, this study elucidated the effect of interval training on muscle and bone health, as well as anti‐ageing, in ovariectomized (OVX) rats. The anti‐ageing effect of IR on muscle and bone was tested using western blotting and micro‐computed tomography analysis, tartrate‐resistant acid phosphatase and immunohistochemical staining. IR significantly inhibited the expression of inflammatory molecules, and improved antioxidant activity via down‐regulation of mitogen‐activated protein kinases (MAPKs) in the ageing‐induced OVX rats skeletal muscle. IR compared with continuous running (CR) improved muscle mass and growth in OVX rats by the promotion of muscle growth‐related factors including MyoD, myogenin, phospho‐mechanistic target of rapamycin (p‐mTOR), sirtuins (SIRTs), and bone morphogenic proteins (BMPs). IR also effectively recovered OVX‐induced bone loss via the down‐regulation of bone resorption and osteoclast formation in receptor activator of nuclear factor κB ligand (RANKL)‐treated bone marrowmacrophages (BMMs). In particular, IR led to high expression of SIRT1 and 6, which promoted osteogenic differentiation and bone formation via modulating the BMP signalling pathway compared with CR training. The in vivo effect of IR was confirmed by immunohistochemical staining with the improvement of bone formation molecules such as BMPs and SIRTs. These results suggested that IR training affected myogenic and osteogenic formation. So, IR training may be considered for prevention of muscle wasting and bone loss for the elderly.

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

Abstract: 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.

Cited by 16 publications

References 52 publications

Multifarious effects of 17-β-estradiol on apolipoprotein E receptors gene expression during osteoblast differentiation <i>in vitro </i>

Multifarious effects of 17-β-estradiol on apolipoprotein E receptors gene expression during osteoblast differentiation <i>in vitro </i>

Atorvastatin Promotes Bone Formation in Aged apoE–/– Mice through the Sirt1–Runx2 Axis

Interval running training improves age‐related skeletal muscle wasting and bone loss: Experiments with ovariectomized rats

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