Ectopic Calcification is Caused by Elevated Levels of Serum Inorganic Phosphate in Mdx Mice

Kikkawa, Namiko; Ohno, Tomohisa; Nagata, Yoichi; Shiozuka, Masataka; Kogure, Toshihiro; Matsuda, Ryoichi

doi:10.1247/csf.08039

Cited by 28 publications

(27 citation statements)

References 41 publications

(40 reference statements)

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“…No connection between PTH and dystrophin has been established previously, but the marked difference in anabolic response to bbPTH in mdx as compared to wild type mouse trabecular bone raises the possibility that dystrophin or associated altered calcium signaling due to dystrophin deficiency could play a role in trabecular bone formation. However, surprisingly there is no difference in serum calcium concentrations between 2 month old mdx and wild type mice [44]. Because of the influence of PTH on calcium homeostasis, it will be important to quantify the effects of PTH on serum ionized calcium concentration in mdx mice in future studies.…”

Section: 1 Discussionmentioning

confidence: 99%

Black bear parathyroid hormone has greater anabolic effects on trabecular bone in dystrophin-deficient mice than in wild type mice

Gray¹,

McGee‐Lawrence²,

Sanders³

et al. 2012

Bone

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Section: 1 Discussionmentioning

confidence: 99%

Black bear parathyroid hormone has greater anabolic effects on trabecular bone in dystrophin-deficient mice than in wild type mice

Gray¹,

McGee‐Lawrence²,

Sanders³

et al. 2012

Bone

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“…56 On the other hand, in addition to being crucial for bone mineralization, Pi acts as a signaling molecule and affects bone cells' physiology and gene expression, including the expression of osteocalcin. 57,58 Thus, ENPP1, ANKH, and ALPL, the central local regulatory factors affecting bone mineralization and Pi levels, may represent one of the main nodes in the regulatory circuit connecting bone and adipose tissues by controlling osteocalcin-plasma levels via Pi concentration.…”

Section: Discussionmentioning

confidence: 99%

Morphological and biochemical features of obesity are associated with mineralization genes’ polymorphisms

et al. 2010

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Background: Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was recently extensively studied as a candidate gene for obesity phenotypes. As the human homologue of the mouse progressive ankylosis (ANKH) and alkaline phosphatase (ALPL) are known functional partners of ENPP1 in bone mineralization, we hypothesized that these genes may also be jointly involved in determining obesity features. Aim: To examine the effects of the three genes, possible gene-sex and gene-gene interactions on variability of four obesity phenotypes: the body mass index (BMI), the waist-hip ratio (WHR), the epidermal growth factor receptor (EGFR), and leptin. Subjects and methods: In all, 962 healthy individuals from 230 families were genotyped for 45 single nucleotide polymorphisms (SNPs). The association analysis was performed using two family based association tests (family based association test and pedigree disequilibrium test). The combined P-values of the two tests were estimated by Monte-Carlo simulations. Relative magnitude of the genetic and familial effects, gene-sex and gene-gene interactions were assessed using variance component models. Results: Associations were observed between ENPP1 polymorphisms and BMI (P ¼ 0.0037) and leptin (P ¼ 0.0068). ALPL markers were associated with WHR (P ¼ 0.0026) and EGFR (P ¼ 0.0001). The ANKH gene was associated with all four studied obesity-related traits (Po0.0184), and its effects were modulated by sex. Gene-gene interactions were not detected. Conclusion: The observed pattern of association signals indicates that ANKH may have a generalized effect on adipose tissue physiology, whereas ENPP1 and ALPL affect distinct obesity features. The joint analysis of related genes and integration of the results obtained by different methods used in this research should benefit other studies of similar design.

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“…For example, dKO mice feature a much shorter life span (ϳ8 wk compared with ϳ2 yr), more necrosis and fibrosis in their skeletal muscles, scoliosis/kyphosis of the spine, and severe cardiac involvement and eventual cardiac failure (14,19,20). The occurrence of FI and HO in the skeletal muscles of mdx mice has been previously described (15), and more extensive HO in dKO mice has also been recently reported by our group (21). IMCL, on the other hand, has not been studied in either mdx or dKO mice or in any other DMD animal models.…”

mentioning

confidence: 89%

RhoA mediates defective stem cell function and heterotopic ossification in dystrophic muscle of mice

Ūsas

Tang

et al. 2013

FASEB j.

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Heterotopic ossification (HO) and fatty infiltration (FI) often occur in diseased skeletal muscle and have been previously described in various animal models of Duchenne muscular dystrophy (DMD); however, the pathological mechanisms remain largely unknown. Dystrophin-deficient mdx mice and dystrophin/utrophin double-knockout (dKO) mice are mouse models of DMD; however, mdx mice display a strong muscle regeneration capacity, while dKO mice exhibit a much more severe phenotype, which is similar to patients with DMD. Our results revealed that more extensive HO, but not FI, occurred in the skeletal muscle of dKO mice versus mdx mice, and RhoA activation specifically occurred at the sites of HO. Moreover, the gene expression of RhoA, BMPs, and several inflammatory factors were significantly up-regulated in muscle stem cells isolated from dKO mice; while inactivation of RhoA in the cells with RhoA/ROCK inhibitor Y-27632 led to reduced osteogenic potential and improved myogenic potential. Finally, inactivation of RhoA signaling in the dKO mice with Y-27632 improved muscle regeneration and reduced the expression of BMPs, inflammation, HO, and intramyocellular lipid accumulation in both skeletal and cardiac muscle. Our results revealed that RhoA represents a major molecular switch in the regulation of HO and muscle regeneration in dystrophic skeletal muscle of mice.

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Ectopic Calcification is Caused by Elevated Levels of Serum Inorganic Phosphate in Mdx Mice

Cited by 28 publications

References 41 publications

Black bear parathyroid hormone has greater anabolic effects on trabecular bone in dystrophin-deficient mice than in wild type mice

Black bear parathyroid hormone has greater anabolic effects on trabecular bone in dystrophin-deficient mice than in wild type mice

Morphological and biochemical features of obesity are associated with mineralization genes’ polymorphisms

RhoA mediates defective stem cell function and heterotopic ossification in dystrophic muscle of mice

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