Phosphate-dependent stimulation of MGP and OPN expression in osteoblasts via the ERK1/2 pathway is modulated by calcium

Khoshniat, Solmaz; Bourgine, Annabelle; Julien, Marion; Petit, Marc; Pilet, Paul; Rouillon, Thierry; Masson, Martial; Gatius, Maithe; Weiss, Pierre; Guicheux, Jérôme; Beck, Laurent

doi:10.1016/j.bone.2010.12.002

Cited by 109 publications

(79 citation statements)

References 50 publications

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“…COL1 plays an important functional role during osteogenesis as it augments the cell adhesion and lays a foundation for OPN, OCN and bone matrix mineralization (21,22). OPN and OCN have high affinity of hydroxyapatite and can specifically integrate with the adhesion and connection of cells and tissues (23). We previously demonstrated that BMP9 alone effectively induces the expression of these markers during osteogenic differentiation (3).…”

Section: Effect Of Tgfβ1 On the Expression Of Osteogenic Markers In Bmentioning

confidence: 99%

Biphasic effects of TGFβ1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells

Deng²,

Hu³

et al. 2012

BMB Reports

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We have found that the previously uncharacterized bone morphogenetic protein-9 (BMP9) is one of the most osteogenic factors. However, it is unclear if BMP9 cross-talks with TGFβ1 during osteogenic differentiation. Using the recombinant BMP9 adenovirus, we find that low concentration of rhTGFβ1 synergistically induces alkaline phosphatase activity in BMP9-transduced C3H10T1/2 cells and produces more pronounced matrix mineralization.

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Section: Effect Of Tgfβ1 On the Expression Of Osteogenic Markers In Bmentioning

confidence: 99%

Biphasic effects of TGFβ1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells

Deng²,

Hu³

et al. 2012

BMB Reports

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“…This has made bone a model of choice to study Pi signaling where it has been shown in early studies to regulate the programmed cell death of hypertrophic chondrocytes (10,11,13). In subsequent studies, we and others have shown that Pi could regulate skeletal mineralization by controlling the expression of the mineralization inhibitors Mgp and Opn through the activation of the ERK1/2 pathway (7,15,16,18,19). Our present study brings evidence for a role of PiT1 and PiT2 in transmitting the Pi signal to the cell by showing that the Pi-dependent upregulation of Mgp and Opn, and ERK1/2 phosphorylation were blunted in PiT1-or PiT2-depleted cells.…”

Section: Discussionmentioning

confidence: 95%

Phosphate (Pi)-regulated heterodimerization of the high-affinity sodium-dependent Pi transporters PiT1/Slc20a1 and PiT2/Slc20a2 underlies extracellular Pi sensing independently of Pi uptake

Bon

Couasnay

Bourgine

et al. 2018

Journal of Biological Chemistry

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“…Both calcium and phosphorus stimulate osteoblasts to form bone matrix and to mineralize it, thereby extracting both minerals from the extracellular fluid and lowering the calcium-phosphorus product (8,17,43,46). Furthermore, it has been shown that this mineralization and bone formation by osteoblasts are associated with an increased expression and release of FGF23 (45).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it has been shown that this mineralization and bone formation by osteoblasts are associated with an increased expression and release of FGF23 (45). It has also been demonstrated that phosphorus-dependent stimulation of the expression of mineralization-associated proteins (e.g., matrix Gla protein and osteopontin) in osteoblasts is modulated by the extracellular calcium via the extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway (17). In addition, the concomitant presence of phosphorus and calcium has been shown to form calciumphosphorus precipitates, which can stimulate ERK1/2 activity (17).…”

Section: Discussionmentioning

confidence: 99%

“…It has also been demonstrated that phosphorus-dependent stimulation of the expression of mineralization-associated proteins (e.g., matrix Gla protein and osteopontin) in osteoblasts is modulated by the extracellular calcium via the extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway (17). In addition, the concomitant presence of phosphorus and calcium has been shown to form calciumphosphorus precipitates, which can stimulate ERK1/2 activity (17). In this way, FGF23 secretion might communicate the state of "mineral balance".…”

Section: Discussionmentioning

confidence: 99%

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Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

Quinn

Thomsen

Pang

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Quinn SJ, Thomsen AR, Pang JL, Kantham L, Bräuner-Osborne H, Pollak M, Goltzman D, Brown EM. Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo. Am J Physiol Endocrinol Metab 304: E310 -E320, 2013. First published December 11, 2012; doi:10.1152/ajpendo.00460.2012.-Calcium and phosphorus homeostasis are highly interrelated and share common regulatory hormones, including FGF23. However, little is known about calcium's role in the regulation of FGF23. We sought to investigate the regulatory roles of calcium and phosphorus in FGF23 production using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR; PTHCaSR DKO). In wild-type, PTH KO, and PTH-CaSR DKO mice, elevation of either serum calcium or phosphorus by intraperitoneal injection increased serum FGF23 levels. In PTH KO and PTH-CaSR DKO mice, however, increases in serum phosphorus by dietary manipulation were accompanied by severe hypocalcemia, which appeared to blunt stimulation of FGF23 release. Increases in dietary phosphorus in PTH-CaSR DKO mice markedly decreased serum 1,25-dihydroxyvitamin D 3 [1,25(OH)2D3] despite no change in FGF23, suggesting direct regulation of 1,25(OH)2D3 synthesis by serum phosphorus. Calcium-mediated increases in serum FGF23 required a threshold level of serum phosphorus of about 5 mg/dl. Analogously, phosphorus-elicited increases in FGF23 were markedly blunted if serum calcium was less than 8 mg/dl. The best correlation between calcium and phosphorus and serum FGF23 was found between FGF23 and the calcium ϫ phosphorus product. Since calcium stimulated FGF23 production in the PTH-CaSR DKO mice, this effect cannot be mediated by the full-length CaSR. Thus the regulation of FGF23 by both calcium and phosphorus appears to be fundamentally important in coordinating the serum levels of both mineral ions and ensuring that the calcium ϫ phosphorus product remains within a physiological range. fibroblast growth factor 23; calcium ϫ phosphorus product; 1,25-dihydroxyvitamin D3; parathyroid hormone; calcium-sensing receptor CALCIUM AND PHOSPHORUS HOMEOSTASIS are highly dependent on one another, and changes in the serum level of either calcium or phosphorus will in many cases lead to secondary changes in the serum level of the other. Fibroblast growth factor 23 (FGF23) is a newly discovered hormone that is implicated in phosphorus homeostasis, and dysregulation of FGF23 may result in several disorders of phosphorus homeostasis (1,24,38). FGF23 is expressed in and released from osteoblasts and osteocytes in response to hyperphosphatemia and 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] (19, 20, 39). In the renal tubule, FGF23 binds to FGF receptors and their cofactor Klotho, causing inhibition of the expression of the sodiumdependent phosphate cotransporters Npt2a and Npt2c, thereby resulting in less renal phosphorus reabsorption (11,21,35,40,41). In addition, FGF23 inhibits expression of the 1␣-hydroxylase enzyme, l...

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Phosphate-dependent stimulation of MGP and OPN expression in osteoblasts via the ERK1/2 pathway is modulated by calcium

Cited by 109 publications

References 50 publications

Biphasic effects of TGFβ1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells

Biphasic effects of TGFβ1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells

Phosphate (Pi)-regulated heterodimerization of the high-affinity sodium-dependent Pi transporters PiT1/Slc20a1 and PiT2/Slc20a2 underlies extracellular Pi sensing independently of Pi uptake

Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

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