Prolonged incubation with Metformin decreased angiogenic potential in human bone marrow mesenchymal stem cells

Montazersaheb, Soheila; Kabiri, Fahimeh; Saliani, Negar; Nourazarian, Alireza; Avci, Çığır Biray; Rahbarghazi‬, Reza; Charoudeh, Hojjatollah Nozad

doi:10.1016/j.biopha.2018.09.135

Cited by 25 publications

(10 citation statements)

References 23 publications

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“…Studies show decreased osteoclastogenesis in murine-derived preosteoclasts using supra-pharmacological concentrations of metformin [196,197,198]. However, some in vitro studies have shown MSC apoptosis following transplantation and decreased angiogenic potential of human MSCs treated with metformin [199,200]. In human-induced pluripotent MSCs, metformin enhanced osteoblastic activity by increasing ALP activity and mineralized nodule formation, which was partly mediated by the LKB1/AMPK pathway [201].…”

Section: Effects Of Insulin and Anti-diabetic Drugsmentioning

confidence: 99%

Impact of Diabetes Mellitus on Bone Health

Murray

Coleman

2019

IJMS

159

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Long-term exposure to a diabetic environment leads to changes in bone metabolism and impaired bone micro-architecture through a variety of mechanisms on molecular and structural levels. These changes predispose the bone to an increased fracture risk and impaired osseus healing. In a clinical practice, adequate control of diabetes mellitus is essential for preventing detrimental effects on bone health. Alternative fracture risk assessment tools may be needed to accurately determine fracture risk in patients living with diabetes mellitus. Currently, there is no conclusive model explaining the mechanism of action of diabetes mellitus on bone health, particularly in view of progenitor cells. In this review, the best available literature on the impact of diabetes mellitus on bone health in vitro and in vivo is summarised with an emphasis on future translational research opportunities in this field.

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Section: Effects Of Insulin and Anti-diabetic Drugsmentioning

confidence: 99%

Impact of Diabetes Mellitus on Bone Health

Murray

Coleman

2019

IJMS

159

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“…Metformin may also play a role in the immunomodulatory potential of MSCs and in their differentiation properties (Gao et al, 2008;Gu et al, 2017). In addition to these positive effects, metformin may promote the apoptosis of MSCs and decrease their angiogenic capacity (Montazersaheb et al, 2018;He et al, 2019). The present study endeavored to combine this piecemeal information in a more comprehensive way.…”

Section: Discussionmentioning

confidence: 99%

Proteomic and Biological Analysis of the Effects of Metformin Senomorphics on the Mesenchymal Stromal Cells

Acar

Ayaz-Güner

Gunaydin

et al. 2021

Front. Bioeng. Biotechnol.

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Senotherapeutics are new drugs that can modulate senescence phenomena within tissues and reduce the onset of age-related pathologies. Senotherapeutics are divided into senolytics and senomorphics. The senolytics selectively kill senescent cells, while the senomorphics delay or block the onset of senescence. Metformin has been used to treat diabetes for several decades. Recently, it has been proposed that metformin may have anti-aging properties as it prevents DNA damage and inflammation. We evaluated the senomorphic effect of 6 weeks of therapeutic metformin treatment on the biology of human adipose mesenchymal stromal cells (MSCs). The study was combined with a proteome analysis of changes occurring in MSCs’ intracellular and secretome protein composition in order to identify molecular pathways associated with the observed biological phenomena. The metformin reduced the replicative senescence and cell death phenomena associated with prolonged in vitro cultivation. The continuous metformin supplementation delayed and/or reduced the impairment of MSC functions as evidenced by the presence of three specific pathways in metformin-treated samples: 1) the alpha-adrenergic signaling, which contributes to regulation of MSCs physiological secretory activity, 2) the signaling pathway associated with MSCs detoxification activity, and 3) the aspartate degradation pathway for optimal energy production. The senomorphic function of metformin seemed related to its reactive oxygen species (ROS) scavenging activity. In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS.

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“…Using the RT2 Pro ler PCR Array, we monitored the expression of 86 genes participating in the atherosclerosis signaling pathway. Raw data were processed using the 2 −ΔΔCT method to determine statistical signi cance between the groups [20].…”

Section: Pcr Arraymentioning

confidence: 99%

Effect of docosahexaenoic acid plus insulin on atherosclerotic human endothelial cells

Abriz

Rahbarghazi‬

Nourazarian

et al. 2020

Preprint

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Background: Atherosclerosis is touted as one of the most critical consequences of diabetes mellitus indicated by local inflammation of endothelial cells. The Effect of Omega 3 fatty acids, mainly docosahexaenoic acid (DHA), has been investigated in cells after exposure to high doses of lipids. The current experiment aimed to address the modulatory effects of docosahexaenoic acid and insulin in palmitic-treated human endothelial cells. Methods: Human umbilical vein endothelial cells were treated with 1mM palmitic acid, 50μM insulin, 50μM docosahexaenoic acid, and their combination for 48 hours. Cell survival rate and apoptosis were measured using MTT and flow cytometry assays. The Griess assay detected NO levels. Protein levels of TNF-α, IL-6, and NF-κB were studied using ELISA and immunofluorescence imaging. The expression of genes participating in atherosclerosis was monitored using PCR array analysis. Results: Oil Red O staining showed the inhibitory effect of DHA and insulin to reduce the intracellular accumulation of palmitic acid. Both DHA and Insulin blunted palmitic acid detrimental effects on HUVECs indicated by an increased survival rate (p<0.05). The percent of apoptotic cells was decreased in palmitic-treated cells received insulin and DHA compared to palmitic-treated group (p<0.05). Based on our data, DHA and Insulin diminished the production of all inflammatory cytokines, TNF-α, IL-6, and NF-κB, in palmitic-treated cells (p<0.05). Similar to these data, NO production was also decreased in all groups treated with insulin and DHA compared to the palmitic-treated cells (p<0.05). PCR array analysis revealed the modulatory effect of DHA and insulin on the expression of atherosclerosis-related genes pre-treated with palmitic acid compared to the control group (p<0.05). Conclusion: DHA and Insulin could alter the dynamic growth and dysfunctional activity of human endothelial cells after treatment with palmitic acid. Taken together, Omega 3 fatty acids, along with insulin, could dictate specific cell behavior in endothelial cells in vitro

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Prolonged incubation with Metformin decreased angiogenic potential in human bone marrow mesenchymal stem cells

Cited by 25 publications

References 23 publications

Impact of Diabetes Mellitus on Bone Health

Impact of Diabetes Mellitus on Bone Health

Proteomic and Biological Analysis of the Effects of Metformin Senomorphics on the Mesenchymal Stromal Cells

Effect of docosahexaenoic acid plus insulin on atherosclerotic human endothelial cells

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