Osteogenic actions of the anti-diabetic drug metformin on osteoblasts in culture

Cortizo, Ana Marı́a; Sedlinsky, Claudia; McCarthy, Antonio Desmond; Blanco, Alcira; Schurman, León

doi:10.1016/j.ejphar.2006.02.030

Cited by 211 publications

(209 citation statements)

References 59 publications

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“…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%

“…It was shown that AICAR and metformin both cause a direct osteogenic effect in MC3T3-E1 cells (Cortizo et al 2006, Kanazawa et al 2007, Jang et al 2011. These actions include a dose-dependent increase in cell proliferation, type I collagen production, alkaline phosphatase (ALP) activity, and mineral deposition.…”

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

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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Section: Ampk and The Skeletal Effects Of Antidiabetic Drugsmentioning

confidence: 99%

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

confidence: 99%

AMP-activated protein kinase pathway and bone metabolism

Jeyabalan

Shah²,

Viollet³

et al. 2011

Journal of Endocrinology

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“…Several studies have indeed shown that TZDs increase fracture risk (10,11). In contrast, metformin, another widely prescribed anti-diabetic drug (12), is osteogenic in vitro (13,14) and reduces the risk of fracture in DM patients (15), as well as inhibiting the bone loss induced by ovariectomy (OVX) in rats (16,17). However, our recent studies showed no beneficial effect of metformin on bone mass and fracture healing in rodents (18).…”

Section: Introductionmentioning

confidence: 99%

Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice

Pereira

Jeyabalan

Jorgensen

et al. 2015

Bone

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“…In contrast, others reported that metformin (1 mM) had no effect on the osteogenic differentiation of MSCs when cultured in β-glycerol phosphate and ascorbic2-phosphate medium (Wu et al 2011). Cortizo et al (2006) also found that metformin had no effect on ALP activity in UMR106 rat osteosarcoma cells. At the concentration of 2 mM, metformin reduced mineralization of osteoblasts (Kasai et al 2009).…”

Section: Discussionmentioning

confidence: 82%

“…Molinuevo et al (2010) found that 10 μM metformin can increase ALP activity and mineralization in rat BM progenitor cells. Cortizo et al (2006) showed that metformin (25-100 μM) can increase type I collagen production and ALP activity in MC3T3E1 cells. Moreover, metformin can reverse rosiglitazoneinduced bone loss in rats (Sedlinsky et al 2011).…”

Section: Discussionmentioning

confidence: 99%

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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Osteogenic actions of the anti-diabetic drug metformin on osteoblasts in culture

Cited by 211 publications

References 59 publications

AMP-activated protein kinase pathway and bone metabolism

AMP-activated protein kinase pathway and bone metabolism

Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice

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

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