Mechanisms involved in altered bone metabolism in diabetes: a narrative review

Ghodsi, Maryam; Larijani, Bagher; Keshtkar, Abbass Ali; Nasli‐Esfahani, Ensieh; Alatab, Sudabeh; Mohajeri-Tehrani, Mohammad Reza

doi:10.1186/s40200-016-0275-1

Cited by 60 publications

(48 citation statements)

References 111 publications

(144 reference statements)

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“…In vitro studies have shown that high glucose weakened osteoblast response to 1,25(OH) 2 D 3 and indirectly down-regulated VDR expression (47). Likewise, our previous study also showed that high glucose attenuated the expression of insulin receptor and VDR, whereas these adverse effects can be reversed by 1,25(OH) 2 D 3 treatment (48).…”

Section: 25(oh) 2 D 3 Promotes Bone Formation With Foxo1 Inactivationmentioning

confidence: 66%

1α,25-Dihydroxyvitamin D3 promotes bone formation by promoting nuclear exclusion of the FoxO1 transcription factor in diabetic mice

Zhang

Xin

et al. 2017

Journal of Biological Chemistry

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1α,25-Dihydroxyvitamin D (1,25(OH)D) is the active form of vitamin D, which is responsible for reducing the risk for diabetes mellitus (DM), decreasing insulin resistance, and improving insulin secretion. Previous studies have shown that 1,25(OH)D inhibited the activity of FoxO1, which has been implicated in the regulation of glucose metabolism. However, its function and mechanism of action in DM-induced energy disorders and also in bone development remains unclear. Here, using and approaches including osteoblast-specific, conditional FoxO1-knock-out mice, we demonstrate that 1,25(OH)D ameliorates abnormal osteoblast proliferation in DM-induced oxidative stress conditions and rescues the impaired glucose and bone metabolism through FoxO1 nuclear exclusion resulting from the activation of PI3K/Akt signaling. Using alizarin red staining, alkaline phosphatase assay, Western blot, and real-time qPCR techniques, we found that 1,25(OH)D promotes osteoblast differentiation and expression of osteogenic phenotypic markers ( alkaline phosphatase (1), collagen 1 (COL-1), osteocalcin (OCN), and osteopontin (OPN)) in a high-glucose environment. Moreover, 1,25(OH)D increased both total OCN secretion and levels of uncarboxylated OCN (GluOC) by phosphorylating FoxO1 and promoting its nuclear exclusion, indicated by Western blot and cell immunofluorescence analyses. Taken together, our findings confirm that FoxO1 is a key mediator involved in glucose homeostasis and indicate that 1,25(OH)D improves glucose metabolism and bone development via regulation of PI3K/Akt/FoxO1/OCN pathway.

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Section: 25(oh) 2 D 3 Promotes Bone Formation With Foxo1 Inactivationmentioning

confidence: 66%

1α,25-Dihydroxyvitamin D3 promotes bone formation by promoting nuclear exclusion of the FoxO1 transcription factor in diabetic mice

Zhang

Xin

et al. 2017

Journal of Biological Chemistry

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“…Thus Ca:Ph ratio was increased. Rise of Ca:P in diet was proposed to prevent bone damage and upsurge intestinal Ca captivation in ovx rats (Ghodsi et al 2016). Contradicting to our data, Gopalakrishnan et al (2006) showed that serum ALP activity was amplified up to threefold in diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

“…In rats with diabetes, osteocalcin and IGF-1 were significantly reduced. Studies showed that diabetes may lead to lower bone turnover index and impairment of both osteoblastic maturity and activity (Ghodsi et al 2016).…”

Section: Discussionmentioning

confidence: 99%

Phenotype of vitamin D receptor gene polymorphisms, impact of feeding flaxseed oil, and osteoporosis in ovariectomised diabetic rats

et al. 2018

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Background:The vitamin D is involved in a wide variety of biological processes including bone metabolism, regulation of cell proliferation and differentiation. Variations in this endocrine system have, thus, been linked to several common diseases, including osteoporosis, diabetes. The aim of study was to evaluate the effect of flaxseed oil on bone homeostasis and whether changes in the levels of the bone formation markers are related to vitamin D receptor (VDR) gene polymorphisms i.e. Bsm1 and Fok1 which have been studied by the restriction fragment length polymorphism (RFLP) technique. Results:The study included rats were classified in groups as control, diabetic, diabetic received flaxseed oil in the diet, ovariectomised (ovx), and ovx-diabetic received flaxseed oil in the diet. Insulin growth factor-1 (IGF-1) urinary deoxypyridinoline (DPD), and osteocalcin were increased (1.470 ± 88.1), (160 ± 7.11), (21.25 ± 2.33) respectively in ovx. and have significantly positive correlation (p < 0.05): their lowest levels were detected. Upon adding flaxseed oil. Bone mineral density (BMD) and content (BMC) were reduced (0.061 ± 0. 0046), (0.041 ± .0048) in all groups and increased (0.070 ± 0.0046), (0.063 ± 0.0045) upon adding flaxseed oil which have a ratio of 13.90 ± 0.01:21.10 ± 0.40 and there is correlation between bone marker and gene polymorphism after receiving flaxseed oil.Conclusion: Diabetes has more pronounced effect on bone health than ovariectomy, and there was effect of gene and flaxseed oil has beneficial effect on the prevention of osteoporosis.

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“…Anyhow, in our study IGF-1 levels correlated with osteocalcin, suggesting a promoting action on osteoblast production. IGF-1 and OC show parallel patterns in different models in literature [28,29], however, studies about skeletal maturation suggest a triggering action on OC synthesis [30].…”

Section: Discussionmentioning

confidence: 99%

Relationships Between Thyroid Hormones, Insulin-Like Growth Factor-1 and Antioxidant Levels in Hypothalamic Amenorrhea and Impact on Bone Metabolism

et al. 2019

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Supplementary Material for this article is available online at http://www.thieme-connect.de/products ABStR AC tReduced bone mineral density (BMD) in Functional Hypothalamic Amenorrhea (FHA) is mainly related to hypoestrogenism, but other hormonal derangement (reduced conversion of T4-T3 and GH resistance) can play a role. These hormones are involved in antioxidant systems regulation. We evaluated the impact of hormonal alterations, with special focus on low T3 and IGF-1 levels, on antioxidant systems as a link with osteoporosis in FHA. Forty-three FHA patients, 15-34 years, with BMI range 17.3-23.4 kg/m 2 , were divided in 2 groups according to fT3 levels; group A (n = 22), low fT3 ( < 2.4 pg/ml) and group B (n = 21), normal fT3 (≥ 2.4 pg/ml). We evaluated hormonal parameters (fT3, fT4, TSH, IGF-1, FSH, LH, estradiol, DHEAS, testosterone, cortisol), bone metabolism (calcium, phosphorus, 25-OH Vitamin D, PTH, β-crosslaps, bone alkaline phosphatase) and total antioxidant capacity (TAC), expressed as LAG (latency time in radical species appearance using spectrophotometric method). BMD was assessed by DEXA. Group A patients exhibited significantly lower levels of .05 ± 15.25 ng/ml) and osteocalcin (17.51 ± 1.14 vs. 21.49 ± 1.56 ng/ml); LAG values were significantly higher in A (66.33 ± 1.74 s) vs. B (54.62 ± 1.74 s). A significant direct correlation was found between both IGF-1 and fT3 with osteocalcin (r² = 0.22, p = 0.0049 and r² = 0.34, p = 0.0001, respectively). No difference in LAG between groups according to IGF-1 were found. These data show a correlation between altered bone turnover and low fT3, which is highly prevalent in FHA. Low fT3 levels may contribute to reduced BMD. Oxidative stress could be the link underlying different bone turnover pattern and endocrine dysfunction in FHA.

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Mechanisms involved in altered bone metabolism in diabetes: a narrative review

Cited by 60 publications

References 111 publications

1α,25-Dihydroxyvitamin D3 promotes bone formation by promoting nuclear exclusion of the FoxO1 transcription factor in diabetic mice

1α,25-Dihydroxyvitamin D3 promotes bone formation by promoting nuclear exclusion of the FoxO1 transcription factor in diabetic mice

Phenotype of vitamin D receptor gene polymorphisms, impact of feeding flaxseed oil, and osteoporosis in ovariectomised diabetic rats

Relationships Between Thyroid Hormones, Insulin-Like Growth Factor-1 and Antioxidant Levels in Hypothalamic Amenorrhea and Impact on Bone Metabolism

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