Methionine synthase reductase polymorphisms are associated with serum osteocalcin levels in postmenopausal women

Kim, Duk Jae; Park, Byung Lae; Koh, Jung‐Min; Kim, Ghi Su; Kim, Lyoung Hyo; Cheong, H. S.; Shin, Hyoung Doo; Hong, Jin Woo; Kim, Sang Woo; Shin, Hong‐In; Park, Eui Kyun; Kim, Shin‐Yoon

doi:10.1038/emm.2006.61

Cited by 18 publications

(10 citation statements)

References 31 publications

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“…Since miRNAs usually inhibit their target gene, this up-regulation of miR-143 is consistent with the downregulation of the Smad4 gene. Since, Mtrr has been found to have a significant correlation with osteocalcin levels and bone turnover, 105 it is interesting that we found a 2.4-fold decrease in fracture healing of alcohol-consuming animals.…”

Section: Developmentmentioning

confidence: 85%

Alcohol induced epigenetic perturbations during the inflammatory stage of fracture healing

Sampson

Chaput²,

J³

et al. 2011

Exp Biol Med (Maywood)

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It is well recognized by orthopedic surgeons that fractures of alcoholics are more difficult to heal successfully and have a higher incidence of non-union, but the mechanism of alcohol's effect on fracture healing is unknown. In order to give direction for the study of the effects of alcohol on fracture healing, we propose to identify gene expression and microRNA changes during the early stages of fracture healing that might be attributable to alcohol consumption. As the inflammatory stage appears to be the most critical for successful fracture healing, this paper focuses on the events at day three following fracture or the stage of inflammation. Sprague-Dawley rats were placed on an ethanol-containing or pair-fed Lieber and DeCarli diet for four weeks prior to surgical fracture. Following insertion of a medullary pin, a closed mid-diaphyseal fracture was induced using a Bonnarens and Einhorn fracture device. At three days' post-fracture, the region of the fracture calluses was harvested from the right hind-limb. RNA was extracted and microarray analysis was conducted against the entire rat genome. There were 35 genes that demonstrated significant increased expression due to alcohol consumption and 20 that decreased due to alcohol. In addition, the expression of 20 microRNAs was increased and six decreased. In summary, while it is recognized that mRNA levels may or may not represent protein levels successfully produced by the cell, these studies reveal changes in gene expression that support the hypothesis that alcohol consumption affects events involved with inflammation. MicroRNAs are known to modulate mRNA and these findings were consistent with much of what was seen with mRNA microarray analysis, especially the involvement of smad4 which was demonstrated by mRNA microarray, microRNA and polymerase chain reaction.

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Section: Developmentmentioning

confidence: 85%

Alcohol induced epigenetic perturbations during the inflammatory stage of fracture healing

Sampson

Chaput²,

J³

et al. 2011

Exp Biol Med (Maywood)

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“…In addition, hyperhomocysteinemia results in increasing production of oxidation products, homocysteine thiolactone and homocysteine mixed disulphides 4,5 , which could directly or indirectly damage bone. Some authors found that hyperhomocysteinemia was associated with serum osteocalcin levels in postmenopausal women 20 . However, the link was not evident in our participants (men and premenopausal women with type 2 diabetes).…”

Section: Discussionmentioning

confidence: 99%

Fracture is additionally attributed to hyperhomocysteinemia in men and premenopausal women with type 2 diabetes

Zhang

Lü

et al. 2013

J of Diabetes Invest

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Aims/Introduction: Data on hyperhomocysteinemia in relation to fractures in diabetes are limited. We aimed to explore the relationship between plasma total homocysteine concentrations and fractures in men and premenopausal women with type 2 diabetes. Materials and Methods: Diabetic and control participants (n = 292) were enrolled in a cross-sectional hospital-based study. Bone mineral density and fractures were documented by dual energy X-ray absorptiometry and X-ray film, respectively. Plasma total homocysteine concentrations were measured using fluorescence polarization immunoassay. Risk factors for low bone mineral density or fractures and determinants of homocysteine were obtained from blood samples and the interviewer questionnaire. Results: Plasma total homocysteine levels were higher in diabetic participants with fractures than without (8.6 [2.1] lmol/L vs 10.3 [3.0] lmol/L, P = 0.000). Diabetic participants with fractures had similar bone mineral densities as control participants. The association of homocysteine with the fracture was independent of possible risk factors for fractures (e.g., age, duration of diabetes, glycated hemoglobin, body mass index, thiazolidenediones and retinopathy) and determinants of homocysteine concentration (e.g., age, sex, serum folate and vitamin B 12 , renal status and biguanide use; odds ratio 1.41, 95% confidence interval 1.05-2.03, P = 0.020). Furthermore, per increase of 5.0 lmol/L plasma homocysteine was related to the fracture, after controlling for per unit increase of other factors (odds ratio 1.42, 95% confidence interval 1.12-1.78, P = 0.013). Conclusions: Plasma total homocysteine concentration is independently associated with occurrence of fractures in men and premenopausal women with type 2 diabetes. Future prospective studies are warranted to clarify the relationship.

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“…Because of contradictory results with the studies, more studies are required to come to a final conclusion. The Hcy-induced fracture risk could be assessed by analyzing bone metabolism markers which are divided into bone formation (alkaline phosphatase, pro-collagen type I N and C-terminal peptides, osteocalcin) [15, 25, 29–31], and bone resorption (collagen I, beta-crosslaps, urinary deoxypyridinoline crosslinks, tartrate resistant acid phosphatase 5b) [30, 32, 33]. However, metabolism anomalies arise after disturbance of normal axis between bone formation and resorption.…”

Section: Historical Perspective and Effect Of Homocystinuria On Bonementioning

confidence: 99%

Mitochondrial epigenetics in bone remodeling during hyperhomocysteinemia

et al. 2014

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Elevated levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), is an independent risk factor of various diseases. Clinical studies report that people born with severe HHcy develop skeletal malformations with weaker bone. Studies also report that altered mitochondrial dynamics and altered epigenetics contribute to weaker bones and bone diseases. Although Hcy-induced mitochondrial dysfunction has been shown to affect bone metabolism, the role of mitochondrial epigenetics (mito-epigenetics) has not been studied in bones. The epigenetics in mitochondria is interesting as the mitochondrial genome size is small (16 kb) with fewer CpG, and without histones and introns. Recently, fascinating works on epigenetics along with the discovery of histone-like proteins in mitochondria are giving exciting areas for novel studies on mitochondria epigenetics. There are mutual cause and effect relationships between bone, mitochondria, Hcy, and epigenetics but unfortunately, studies are lacking which describe the involvement of all these together in bone disease progression. This review describes the reciprocal relationships and mechanisms of Hcy-bone-mitochondria-epigenetics along with a short discussion of techniques which could be employed to assess Hcy-induced anomaly in bone, mediated through alterations in mitochondrial epigenetics.

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Methionine synthase reductase polymorphisms are associated with serum osteocalcin levels in postmenopausal women

Cited by 18 publications

References 31 publications

Alcohol induced epigenetic perturbations during the inflammatory stage of fracture healing

Alcohol induced epigenetic perturbations during the inflammatory stage of fracture healing

Fracture is additionally attributed to hyperhomocysteinemia in men and premenopausal women with type 2 diabetes

Mitochondrial epigenetics in bone remodeling during hyperhomocysteinemia

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