Metformin reverses the deleterious effects of high glucose on osteoblast function

Zhen, Donghu; Chen, Yirong; Tang, Xulei

doi:10.1016/j.jdiacomp.2009.05.002

Cited by 151 publications

(122 citation statements)

References 34 publications

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“…High dose metformin can inhibit the growth of tumor cells (He et al 2015). In contrast, low dose metformin (0.64 μM) can increase the proliferation of rat primary osteoblasts (Zhen et al 2010). In the present study, our data clearly showed that low dose (0.05 mM) metformin exerted no noticeable effects on the proliferation of human CV-MSCs.…”

Section: Discussioncontrasting

confidence: 39%

Metformin Enhances Osteogenesis and Suppresses Adipogenesis of Human Chorionic Villous Mesenchymal Stem Cells

Yang

et al. 2017

Tohoku J. Exp. Med.

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Metformin is the first-line anti-hyperglycemic drugs commonly used to treat type 2 diabetes. Recent studies have shown that metformin can enhance bone formation through induction of endothelial nitric oxide synthase (eNOS). Human chorionic villous mesenchymal stem cells (CV-MSCs) are promising candidates for regenerative medicine. The present study aimed to investigate the effects of metformin on the osteogenic and adipocytic differentiation of human CV-MSCs, and to elucidate the underlying mechanism. CV-MSCs, prepared from human term placentae, were cultured with different concentrations of metformin. Treatment for 72 hours with 0.05 mM metformin had no noticeable effect on the proliferation of CV-MSCs. Consequently, CV-MSCs were cultured for seven or 14 days in the osteogenic medium supplemented with 0.05 mM metformin. Treatment for seven days with metformin increased the expression levels of osteogenic protein mRNAs, including alkaline phosphatase, runt-related transcription factor 2, and osteopontin. Metformin also enhanced the mineralization of CV-MSCs. Furthermore, metformin induced the expression of eNOS in CV-MSCs during osteogenic differentiation. By contrast, when CV-MSCs were cultured for 14 days in the adipogenic medium, 0.05 mM metformin inhibited the expression of adipogenic protein mRNAs, including proliferators-activated receptor-γ and CCAAT/enhancer binding protein-α. The lipid droplet accumulation was also reduced on 28 days after metformin treatment. These findings indicate that metformin can enhance osteogenic differentiation of CV-MSCs and reduce adipocyte formation. The effect of metformin on osteogenic differentiation of CV-MSCs may be associated with eNOS expression. Our findings will highlight the therapeutic potential of metformin in osteoporosis and bone fracture.

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Section: Discussioncontrasting

confidence: 39%

Metformin Enhances Osteogenesis and Suppresses Adipogenesis of Human Chorionic Villous Mesenchymal Stem Cells

Yang

et al. 2017

Tohoku J. Exp. Med.

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“…5 and 100 mM, dose-dependently stimulated bone nodule formation, while AMPK inhibitor compound C dose-dependently reduced bone formation (Shah et al 2010). In this model, metformin also markedly increased cell proliferation and ALP activity (Zhen et al 2010), while AICAR preferentially stimulated ALP activity after 14 days of culture, during the mineralizing phase (Shah et al 2010). When primary osteoblasts were co-treated with AICAR and compound C, compound C suppressed the stimulatory effect of AICAR on bone nodule formation, supporting a role for AMPK activation in bone formation.…”

Section: Effect Of Ampk Activation On Bone Cell Activities In Vitro Amentioning

confidence: 63%

“…The action of metformin on bone marrow mesenchymal cell progenitors has also been investigated and metformin similarly causes an increase in ALP activity, collagen synthesis, osteocalcin production, and extracellular calcium deposition in vitro, possibly by increasing the expression of RUNX2 (Molinuevo et al 2010). We and others (Shah et al 2010, Zhen et al 2010) have used primary osteoblasts derived from rat calvaria to study the effect of AMPK activation in an in vitro model of bone formation in which the production and the mineralization of a bone matrix, can be assessed quantitatively (Utting et al 2006). We confirmed in this model that both AICAR and metformin, at doses ranging between 0 .…”

Section: Effect Of Ampk Activation On Bone Cell Activities In Vitro Amentioning

confidence: 95%

“…In contrast, metformin induces an osteogenic effect in vivo and in vitro, possibly mediated via RUNX2 and activation of AMPK (Cortizo et al 2006, Gao et al 2010, Molinuevo et al 2010, Zhen et al 2010. Co-treatment of BMPC with metformin partially inhibits the adipogenic action of rosiglitazone (Molinuevo et al 2010).…”

Section: Ampk and The Skeletal Effects Of Antidiabetic Drugsmentioning

confidence: 99%

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AMP-activated protein kinase pathway and bone metabolism

Jeyabalan

Shah²,

Viollet³

et al. 2011

Journal of Endocrinology

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There is increasing evidence that osteoporosis, similarly to obesity and diabetes, could be another disorder of energy metabolism. AMP-activated protein kinase (AMPK) has emerged over the last decade as a key sensing mechanism in the regulation of cellular energy homeostasis and is an essential mediator of the central and peripheral effects of many hormones on the metabolism of appetite, fat and glucose. Novel work demonstrates that the AMPK signaling pathway also plays a role in bone physiology. Activation of AMPK promotes bone formation in vitro and the deletion of a or b subunit of AMPK decreases bone mass in mice. Furthermore, AMPK activity in bone cells is regulated by the same hormones that regulate food intake and energy expenditure through AMPK activation in the brain and peripheral tissues. AMPK is also activated by antidiabetic drugs such as metformin and thiazolidinediones (TZDs), which also impact on skeletal metabolism. Interestingly, TZDs have detrimental skeletal side effects, causing bone loss and increasing the risk of fractures, although the role of AMPK mediation is still unclear. These data are presented in this review that also discusses the potential roles of AMPK in bone as well as the possibility for AMPK to be a future therapeutic target for intervention in osteoporosis.

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“…In bilateral ovariectomized rats, metformin was shown to improve bone mass and quality [10]. Metformin also protects osteoblasts from the deleterious effects of hyperglycemia and AGEs [11]. Furthermore, it stimulates osteoprotegerin, which prevents osteoclast activity [12].…”

Section: Introductionmentioning

confidence: 99%

Effects of Metformin Alone or in Combination With Insulin on Bone Mineral Density in Osteopenic Patients With Type 2 Diabetes

Awoniyi

2014

J Endocrinol Metab

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Metformin reverses the deleterious effects of high glucose on osteoblast function

Cited by 151 publications

References 34 publications

Metformin Enhances Osteogenesis and Suppresses Adipogenesis of Human Chorionic Villous Mesenchymal Stem Cells

Metformin Enhances Osteogenesis and Suppresses Adipogenesis of Human Chorionic Villous Mesenchymal Stem Cells

AMP-activated protein kinase pathway and bone metabolism

Effects of Metformin Alone or in Combination With Insulin on Bone Mineral Density in Osteopenic Patients With Type 2 Diabetes

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