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The influence of a high fat diet on bone and soft tissue formation in Matrix Gla Protein knockout mice.

ABSTRACT: Studies suggest bone growth and development are influenced by maternal nutrition, during intrauterine and early postnatal life. This study assessed the role of MGP and a maternal high fat diet on vitamin K-dependent proteins' gene expression and their impact on bone formation. Knockout (KO) offspring were smaller than wild type (WT) littermates, yet possessed the same volume of intrascapular brown adipose tissue. The total proportion of body fat was reduced, but only in animals on a control diet. Lung air volume was observed to be comparable in both KO and WT animals on the same diet. The degree of aortic calcification was reduced in KO animals maintained on a HF diet. KO females on the high fat diet showed reduced cortical bone volume and thickness in the femur and tibia. Gene expression levels of GGCX and VKOR were reduced in control fed KO animals suggesting a potential link between gene expression levels of MGP, GGCX, and VKOR and total volumes of bone, calcified soft tissue, and iBAT; with implications for modulation of body length and mass. Our results confirm the important role for vitamin K in bone and calcified soft tissue, but now extend this role to include iBAT.

SUBMITTER: Lanham SA

PROVIDER: S-EPMC5827663 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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The influence of a high fat diet on bone and soft tissue formation in Matrix Gla Protein knockout mice.

Lanham S A SA Cagampang F R FR Oreffo R O C ROC

Scientific reports 20180226 1

Studies suggest bone growth and development are influenced by maternal nutrition, during intrauterine and early postnatal life. This study assessed the role of MGP and a maternal high fat diet on vitamin K-dependent proteins' gene expression and their impact on bone formation. Knockout (KO) offspring were smaller than wild type (WT) littermates, yet possessed the same volume of intrascapular brown adipose tissue. The total proportion of body fat was reduced, but only in animals on a control diet ...[more]

PMID: 29483527

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Project description:Objective: Studies suggest that matrix Gla protein (MGP) is associated with osteoporosis. However, the precise mechanism through which MGP regulates bone metabolism is not fully understood. The purpose of this study was to clarify the role of MGP in bone metabolism. Methods: The MGP gene in MG63 cell line was knocked down using shRNA. Cell Counting Kit-8 assay was used to detect the proliferation of MG63 cells. Moreover, the differentiation and mineralization of MG63 cells were measured through alkaline phosphatase staining and Alizarin Red S staining. Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to detect the protein and mRNA levels of components of the Wnt/β-catenin signaling pathway, such as Wnt3a, β-catenin, and Runx2. Transgenic (MGP+) mice were used to detect the effects of MGP in vivo. Results: The Cell Counting Kit-8 assay suggested that upregulated MGP could promote the proliferation of MG63 cells, whereas its downregulation inhibited proliferation. The alkaline phosphatase assay and Alizarin Red S staining showed that overexpressed MGP led to prominently upregulated differentiation and mineralization of MG63 cells. Conversely, knockdown of MGP decreased the levels of differentiation and mineralization. Western blotting and quantitative reverse transcription-polymerase chain reaction showed that overexpression of MGP upregulated Wnt3a, β-catenin, and Runx2. In contrast, knocking down MGP reduced their transcriptional levels. In vivo, overexpression of MGP inhibited the decrease in bone mineral density induced via ovariectomy in the femur, and significantly prevented bone volume fraction, trabecular number, BV/TV, and TbTh to decrease. In addition, it increased the levels of estradiol in sera. Conclusion: The findings of this study suggest that the promotion of osteoblast proliferation, differentiation, and mineralization by MGP may be a mechanism to prevent osteoporosis. Furthermore, the results show that MGP promoted the osteogenic effects via the Wnt/β-catenin signaling pathway.

Dataset Information

The influence of a high fat diet on bone and soft tissue formation in Matrix Gla Protein knockout mice.

Publications

The influence of a high fat diet on bone and soft tissue formation in Matrix Gla Protein knockout mice.

Similar Datasets

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