Mitochondrial epigenetics in bone remodeling during hyperhomocysteinemia

Kalani, Anuradha; Kamat, Pradip K.; Voor, Michael J.; Tyagi, Suresh C.; Tyagi, Neetu

doi:10.1007/s11010-014-2114-3

Cited by 23 publications

(14 citation statements)

References 82 publications

(89 reference statements)

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“…Additionally neural tube defects, congenital heart defects, and nonsyndromic oral cleft, which appear to be related to hyperhomocysteinemia (15,70,95), might be characterized by epigenetic abnormalities. Recently a potential link between homocysteine, mitochondrial epigenetics, and bone remodeling was identified, suggesting the homocysteine synthesis could be another key regulatory point of epigenetic mechanisms (47,94). However, the mechanisms of this relationship needs to be fully understood.…”

Section: Mitochondrial Dna Methylation: New Frontier Of Cross Talkmentioning

confidence: 99%

The mitochondrial side of epigenetics

Castegna

Iacobazzi

Infantino

2015

Physiological Genomics

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The bidirectional cross talk between nuclear and mitochondrial DNA is essential for cellular homeostasis and proper functioning. Mitochondria depend on nuclear contribution for much of their functionality, but their activities have been recently recognized to control nuclear gene expression as well as cell function in many different ways. Epigenetic mechanisms, which tune gene expression in response to environmental stimuli, are key regulatory events at the interplay between mitochondrial and nuclear interactions. Emerging findings indicate that epigenetic factors can be targets or instruments of mitochondrial-nuclear cross talk. Additionally, the growing interest into mtDNA epigenetic modifications opens new avenues into the interaction mechanisms between mitochondria and nucleus. In this review we summarize the points of mitochondrial and nuclear reciprocal control involving epigenetic factors, focusing on the role of mitochondrial genome and metabolism in shaping epigenetic modulation of gene expression. The relevance of the new findings on the methylation of mtDNA is also highlighted as a new frontier in the complex scenario of mitochondrial-nuclear communication.

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Section: Mitochondrial Dna Methylation: New Frontier Of Cross Talkmentioning

confidence: 99%

The mitochondrial side of epigenetics

Castegna

Iacobazzi

Infantino

2015

Physiological Genomics

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“…MR improves health by improving insulin sensitivity and glucose metabolism with reduced accumulation of hepatic triglycerides [Perrone et al, ; Plaisance et al, ], oxidative stress [Caro et al, ; Johnson and Johnson, ], and adiposity in many of the depots in the body [Lees et al, ]. Although these are wonderful benefits, it is not clear whether all tissues will benefit from MR. Growth restriction was seen in young male rodents on MR [Ables et al, ; Huang et al, ] and mice on MR become hyperhomocysteinemic, which could lead to reduced blood flow in bone and retard growth [Tyagi et al, ; Vijayan et al, ; Kalani et al, ]. In rats and mice, MR was reported to reduce bone mass density and mineral content when compared to bones of CF mice [Ables et al, ; Huang et al, ].…”

Section: Discussionmentioning

confidence: 99%

Methionine‐Restricted Diet Increases miRNAs That Can Target RUNX2 Expression and Alters Bone Structure in Young Mice

Plummer

Park

Perodin

et al. 2016

J of Cellular Biochemistry

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Dietary methionine restriction (MR) increases longevity and improves healthspan in rodent models. Young male C57BL/6J mice were placed on MR to assess effects on bone structure and formation. Mice were fed diets containing 0.86% or 0.12% methionine for 5 weeks. Fasting blood plasma was analyzed for metabolic and bone-related biomarkers. Tibiae were analyzed by histomorphometry, while femurs were analyzed by micro-CT and biomechanically using 4-point bending. MR mice had reduced plasma glucose and insulin, while FGF21 and FGF23 increased. Plasma levels of osteocalcin and osteoprotegrin were unaffected, but sclerostin and procollagen I decreased. MR induced bone marrow fat accretion, antithetical to the reduced fat depots seen throughout the body. Cortical bone showed significant decreases in Bone Tissue Density (BTD). In trabecular bone, mice had decreased BTD, bone surface, trabecula and bone volume, and trabecular thickness. Biomechanical testing showed that on MR, bones were significantly less stiff and had reduced maximum load and total work, suggesting greater fragility. Reduced expression of RUNX2 occurred in bone marrow of MR mice. These results suggest that MR alters bone remodeling and apposition. In MR mice, miR-31 in plasma and liver, and miR-133a, miR-335-5p, and miR-204 in the bone marrow was elevated. These miRNAs were shown previously to target and regulate Osterix and RUNX2 in bone, which could inhibit osteoblast number and function. Therefore, dietary MR in young animals alters bone structure by increasing miRNAs in bone and liver that can target RUNX2.

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“…The underlying mechanisms between plasma Hcy levels and fractures are uncertain. The potential mechanisms include the regulative role of Hcy on bone tissue quality through altering the properties of collagen crosslink [ 25 ], affecting bone resorption by stimulating osteoclast formation and activity [ 26 ], and inducing mitochondrial dysfunction [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of B Vitamin (Folate, B6, and B12) Supplementation on Osteoporotic Fracture and Bone Turnover Markers: A Meta-Analysis

Ruan¹,

Gong²,

Jinsong³

et al. 2015

Med Sci Monit

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BackgroundB vitamins (including folate, B6, and B12) supplementation can effectively and easily modify high plasma homocysteine (Hcy). However, the role of Hcy in the pathogenesis of osteoporotic fracture and bone turnover is still controversial. This meta-analysis aimed to assess the impact of B vitamin supplementation on occurrence of any osteoporotic fracture and bone turnover by pooling the results of previous studies.Material/MethodsRelevant randomized controlled trials (RCTs) were searched in databases. Data integration and analysis were done by using Review Manager 5.3 (the Cochrane Collaboration). The risk ratio (RR) and corresponding 95% confidence intervals (CI) of fracture (intervention vs. control) were estimated. Changes in bone turnover indicators (continuous data), weighted mean difference (WMD), and corresponding 95% (CI) were pooled for estimation.ResultsBased on the results of 4 RCTs, this meta-analysis failed to identify a risk-reducing effect of daily supplementation of B vitamins on osteoporotic fracture in patients with vascular disease and with relatively normal plasma Hcy. In addition, we also did not find any positive effects of B vitamin supplementation on bone turnover.ConclusionsB vitamin supplementation might not be effective in preventing fracture and improving bone turnover. However, the possible benefits in selective populations, such as populations with very high plasma Hcy and from regions without B vitamin fortification should be explored in the future.

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Mitochondrial epigenetics in bone remodeling during hyperhomocysteinemia

Cited by 23 publications

References 82 publications

The mitochondrial side of epigenetics

The mitochondrial side of epigenetics

Methionine‐Restricted Diet Increases miRNAs That Can Target RUNX2 Expression and Alters Bone Structure in Young Mice

Effect of B Vitamin (Folate, B6, and B12) Supplementation on Osteoporotic Fracture and Bone Turnover Markers: A Meta-Analysis

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