Abnormal modulation of serum osteocalcin by dietary phosphate and 1,25-dihydroxyvitamin D3 in the hypophosphatemic mouse

Tsuji, Hideaki; Cawthorn, C.; Ecarot, B.

doi:10.1002/jbmr.5650110907

Cited by 8 publications

(1 citation statement)

References 37 publications

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“…Importantly, uncarboxylated form of OCN promotes insulin secretion to affect glucose metabolism by means of stimulating glucagons-like peptide-1 (GLP-1) [55]. OCN circulation can be attenuated by dietary phosphorus supplementation [56], implying functions of phosphorus in regulating OCN secretion and function. Of note, our work revealed restored OCN levels and insulin levels after mineral homeostasis recovery in PUG mice, followed by restored glucose tolerance and insulin sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model

Zou

Xiong

Lai

et al. 2015

Sci. China Life Sci.

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Bone was reported as a crucial organ for regulating glucose homeostasis. In this study, we found that Phex mutant mice (PUG), a model of human X-linked hypophosphatemic rickets (XLH), displayed metabolic abnormality in addition to abnormal phosphate homeostasis, skeletal deformity and growth retardation. Glucose tolerance was elevated with enhanced insulin sensitivity in PUG, though circulating insulin level decreased. Interestingly, bone mineral density defects and glucose metabolic abnormality were both rescued by adding phosphorus-and calcium-enriched supplements in daily diet. Serum insulin level, glucose tolerance and insulin sensitivity showed no differences between PUG and wild-type mice with rescued osteocalcin (OCN) following treatment. Our study suggested that OCN is a potential mediator between mineral homeostasis and glucose metabolism. This investigation brings a new perspective on glucose metabolism regulation through skeleton triggered mineral homeostasis and provides new clues in clinical therapeutics of potential metabolic disorders in XLH patients. glucose metabolism, mineral homeostasis, bone, Phex, X-linked hypophosphatemic rickets Citation:Zou JH, Xiong XW, Lai BB, Sun M, Tu X, Gao X. Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model. [5,6]. In the past decades, bone was studied as an endocrinal organ [7,8]. Interactions between bone and energy metabolism aroused extensive interests and concerns [911]. Phex is mainly expressed in osteoblasts and odontoblasts [1214] and its mutations lead to reduced 1,25-(OH) 2 D 3 and elevated circulating FGF23 (fibroblast growth factor 23) [1517]. 1,25-(OH) 2 D 3 and its receptor could influence expression of uncoupling protein (UCP) in adipocytes [18,19]. In vitro studies demonstrate that the role of 1,25-(OH) 2 D 3 in lipid metabolism is regulator of peroxisome proliferator-activated receptor alpha (Ppara) [20]. Circulating FGF23 is also associated with fat mass and serum lipids [21]. In mouse models of XLH, like Hyp mice, decreased renal glucose reabsorption activity [22], increased glucose production in renal proximal tubules [23] and osteoblasts [24] were observed. The only known physiological substrate of PHEX protein, acidic serine aspartate-rich MEPE associated motif (ASARM peptide), could regulate glucose metabolism and insulin signaling [14]. The above findings indicate PHEXmediated association between skeletal function and energy

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Section: Discussionmentioning

confidence: 99%

Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model

Zou

Xiong

Lai

et al. 2015

Sci. China Life Sci.

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Molecular profile of osteoprogenitor cells seeded on allograft bone

Smith

Huang

et al. 2010

J Tissue Eng Regen Med

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In order to optimize and modulate bone formation it is essential to understand the expression patterns of key bone-specific growth factors, as osteoprogenitor cells undergo the processes of proliferation, differentiation and maturation. This study reports the sequential expression of bone-related growth and transcription factors when bone marrow-derived osteoprogenitor cells from C57BL mice were cultured on allograft bone discs. Mineralization and osteocalcin protein levels were used to track osteogenic differentiation and maturation. Bone-related growth factors, such as Bmp-2, Bmp-7, Ctnnb-1, Fgf-2, Igf-1, Vegf-a and Tgf-β1, and transcription factors, such as Runx-2 and osteocalcin, were examined by enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). Total density of mineralized bone was significantly increased 7.6 ± 0.7% in allografts cultured with cells, compared with a 0.5 ± 2.0% increase in the controls without cells (p < 0.01). Osteocalcin protein levels peaked at day 4. Protein expression showed peaks of BMP-2 and TGF-β1 on day 2, with VEGF peaking on day 8, and IGF-1 decreasing on day 2. mRNA for Pdgf-a peaked on day 2; Bmp-2 on days 4 and 16; Ctnnb-1 on days 8 and 20; Vegf-a, Fgf-2, Runx-2 and Igf-1 on day 12; Tgf-β1 on day 16; and Pdgf-b on day 20. Osteogenic growth factors correlated with Runx-2 and Ctnnb-1, whereas a predominant vascular growth factor, Vegf-a, did not follow this pattern. Specific bone-related genes and proteins were expressed in a time-dependent manner when osteoprogenitor cells were cultured on cortico-cancellous bone discs in vitro.

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Development and Application of a Synthetic Peptide-Based Osteocalcin Assay for the Measurement of Bone Formation in Mouse Serum

et al. 2000

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The mouse is frequently used as an animal model to study skeletal mechanisms relevant to humans. Biochemical markers of bone formation and resorption provide one of the key parameters for assessing skeletal metabolism. One biochemical marker that has proven to be useful in the studies of mouse skeletal metabolism is osteocalcin. Assay for osteocalcin is available in the mouse. The present study describes development of an osteocalcin radioimmunoassay (RIA) using a synthetic peptide. Intact osteocalcin purified from mouse bone extracts shows parallel displacement with synthetic peptide. Sensitivity of the RIA was 19 ng/ml. The average (n = 9) intra- and interassay coefficient of variation for two controls was less than 10%; the averaged recoveries were 106%. The osteocalcin concentration measured by peptide RIA shows a high correlation (r = 0.88, n = 117, P < 0.0001) with an intact osteocalcin assay. In addition, when the intact assay and peptide assays were applied to evaluate skeletal perturbation, similar results were obtained. Accordingly, osteocalcin levels measured by both intact and peptide-based RIA in 8-week C57BL/6J (n = 8) mice treated with PTH 1-34 were twofold higher compared with the vehicle-treated control group. Further studies of the application of the peptide-based RIA for osteocalcin revealed that osteocalcin levels in 4-week postovariectomized (OVX) C57BL/6N mice (n = 10) were 80% higher than the sham-operated (n = 10) mice receiving vehicle. OVX mice receiving weekly injections of estradiol (400 microg/kg body weight) were 38% lower compared with the OVX group treated with vehicle. In conclusion, the peptide-based RIA has analytical and a discriminative power similar to that of the intact osteocalcin assay but has the advantage that the resources for this assay are much easier to accrue.

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Abnormal modulation of serum osteocalcin by dietary phosphate and 1,25-dihydroxyvitamin D3 in the hypophosphatemic mouse

Cited by 8 publications

References 37 publications

Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model

Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model

Molecular profile of osteoprogenitor cells seeded on allograft bone

Development and Application of a Synthetic Peptide-Based Osteocalcin Assay for the Measurement of Bone Formation in Mouse Serum

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