Vitamin D Represses Dentin Matrix Protein 1 in Cementoblasts and Osteocytes

Abstract

Calcium and phosphorus homeostasis is achieved by interplay among hormones, including 1,25(OH)₂D₃ (1,25D), parathyroid hormone, and fibroblast growth factor 23 (FGF23), and their interactions with other proteins. For example, mutations in dentin matrix protein 1 (DMP-1) result in increased FGF23 and hypophosphatemic rickets. 1,25D is reported to modulate FGF23; thus, we hypothesized that 1,25D may be involved in modulating DMP-1 in an intermediary step. Murine cementoblasts (OCCM-30) and osteocyte-like cells (MLO-Y4 and MLO-A5), known to express DMP-1, were used to analyze effects of 1,25D on DMP-1 expression in vitro. DMP-1 mRNA levels decreased by 50% (p < .05) in the presence of 1,25D in all cell types, while use of a vitamin D receptor (VDR) agonist (EB1089) and antagonist (23S,25S)-DLAM-2P confirmed that VDR pathway activation was required for this response. Further analysis showed that histone deacetylase recruitment was necessary, but neither protein kinase A nor C pathways were required. In conclusion, our results support the hypothesis that 1,25D regulates DMP-1 expression through a VDR-dependent mechanism, possibly contributing to local changes in bone/tooth mineral homeostasis.

Keywords

Vitamin D receptor phosphate homeostasis osteogenesis SIBLING family fibroblast growth factor 23 phosphate regulating endopeptidase homolog

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References

Bai

Wang

Cui

(2013). Activation of the ERK1/2 signaling pathway during the osteogenic differentiation of mesenchymal stem cells cultured on substrates modified with various chemical groups. Biomed Res Int 2013:361906.

Barthel

Mathern

Whitfield

Haussler

Hopper

4th Hsieh

. (2007). 1,25-Dihydroxyvitamin D3/VDR-mediated induction of FGF23 as well as transcriptional control of other bone anabolic and catabolic genes that orchestrate the regulation of phosphate and calcium mineral metabolism. J Steroid Biochem Mol Biol 103:381-388.

David

Martin

Hedge

Drezner

Rowe

(2011). ASARM peptides: PHEX-dependent and -independent regulation of serum phosphate. Am J Physiol Renal Physiol 300:F783-F791.

D’Errico

Berry

Ouyang

Strayhorn

Windle

Somerman

(2000). Employing a transgenic animal model to obtain cementoblasts in vitro. J Periodontol 71:63-72.

Ecarot

Desbarats

(1999). 1,25-(OH)2D3 down-regulates expression of Phex, a marker of the mature osteoblast. Endocrinology 140:1192-1199.

Farrow

Davis

Ward

Summers

Bubbear

Keen

. (2009). Molecular analysis of DMP1 mutants causing autosomal recessive hypophosphatemic rickets. Bone 44:287-294.

Haussler

Whitfield

Kaneko

Forster

Saini

Hsieh

. (2012). The role of vitamin D in the FGF23, klotho, and phosphate bone-kidney endocrine axis. Rev Endocr Metab Disord 13:57-69.

Hines

Kolek

Jones

Serey

Sirjani

Kiela

. (2004). 1,25-Dihydroxyvitamin D3 down-regulation of PHEX gene expression is mediated by apparent repression of a 110 kDa transfactor that binds to a polyadenine element in the promoter. J Biol Chem 279:46406-46414.

Huang

Maciejewska

Sun

Peng

Qin

. (2008). Identification of full-length dentin matrix protein 1 in dentin and bone. Calcif Tissue Int 82:401-410.

10.

Ishizuka

Kurihara

Hiruma

Miura

Namekawa

Tamura

. (2008). 1alpha,25-Dihydroxyvitamin D(3)-26,23-lactam analogues function as vitamin D receptor antagonists in human and rodent cells. J Steroid Biochem Mol Biol 110:269-277.

11.

Ito

Findlay

Anderson

Bonewald

Atkins

(2013). Extracellular phosphate modulates the effect of 1α,25-dihydroxy vitamin D3 (1,25D) on osteocyte like cells. J Steroid Biochem Mol Biol 136:183-186.

12.

Kato

Windle

Koop

Mundy

Bonewald

(1997). Establishment of an osteocyte-like cell line, MLO-Y4. J Bone Miner Res 12:2014-2023.

13.

Kato

Boskey

Spevak

Dallas

Hori

Bonewald

(2001). Establishment of an osteoid preosteocyte-like cell MLO-A5 that spontaneously mineralizes in culture. J Bone Miner Res 16:1622-1633.

14.

Kolek

Hines

Jones

LeSueur

Lipko

Kiela

. (2005). 1alpha,25-Dihydroxyvitamin D3 upregulates FGF23 gene expression in bone: the final link in a renal-gastrointestinal-skeletal axis that controls phosphate transport. Am J Physiol Gastrointest Liver Physiol 289:G1036-G1042.

15.

Liu

Zhou

Tang

Menard

Feng

Quarles

(2008). Pathogenic role of Fgf23 in Dmp1-null mice. Am J Physiol Endocrinol Metab 295:E254-E261.

16.

Lochner

Moolman

(2006). The many faces of H89: a review. Cardiovasc Drug Rev 24:261-274.

17.

Martin

Liu

David

Karydis

Feng

. (2011). Bone proteins PHEX and DMP1 regulate fibroblastic growth factor Fgf23 expression in osteocytes through a common pathway involving FGF receptor (FGFR) signaling. FASEB J 25:2551-2562.

18.

Murayama

Takeyama

Kitanaka

Kodera

Hosoya

Kato

(1998). The promoter of the human 25-hydroxyvitamin D3 1 alpha-hydroxylase gene confers positive and negative responsiveness to PTH, calcitonin, and 1 alpha,25(OH)2D3. Biochem Biophys Res Commun 249:11-16.

19.

Murayama

Kim

Yanagisawa

Takeyama

Kato

(2004). Transrepression by a liganded nuclear receptor via a bHLH activator through co-regulator switching. EMBO J 23:1598-1608.

20.

Nagata

Yokota

Ohishi

Nishikawa

Shinohara

Wakano

. (1994). 1 alpha,25-dihydroxyvitamin D3 stimulation of osteopontin expression in rat clonal dental pulp cells. Arch Oral Biol 39:775-782.

21.

Narayanan

Ramachandran

Hao

Park

Cho

. (2003). Dual functional roles of dentin matrix protein 1: implications in biomineralization and gene transcription by activation of intracellular Ca2+ store. J Biol Chem 278:17500-17508.

22.

Okazaki

Nishimori

Ogata

Fujita

(2003). Vitamin D–dependent recruitment of DNA-PK to the chromatinized negative vitamin D response element in the PTHrP gene is required for gene repression by vitamin D. Biochem Biophys Res Commun 304:632-637.

23.

Pike

Meyer

Bishop

(2012). Regulation of target gene expression by the vitamin D receptor: an update on mechanisms. Rev Endocr Metab Disord 13:45-55.

24.

Shimada

Kakitani

Yamazaki

Hasegawa

Takeuchi

Fujita

. (2004). Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 113:561-568.

25.

Siyam

Wang

Qin

Mues

Stevens

D’Souza

. (2012). Nuclear localization of DMP1 proteins suggests a role in intracellular signaling. Biochem Biophys Res Commun 424:641-646.

26.

Tada

Nemoto

Foster

Somerman

Shimauchi

(2011). Phosphate increases bone morphogenetic protein-2 expression through cAMP-dependent protein kinase and ERK1/2 pathways in human dental pulp cells. Bone 48:1409-1416.

27.

Tovar Sepulveda

Falzon

(2003). Prostate cancer cell type-specific regulation of the human PTHrP gene via a negative VDRE. Mol Cell Endocrinol 204:51-64.

28.

Wu-Zhang

Newton

(2013). Protein kinase C pharmacology: refining the toolbox. Biochem J 452:195-209.

29.

Yuan

Takaiwa

Clemens

Feng

Kumar

Rowe

. (2008). Aberrant Phex function in osteoblasts and osteocytes alone underlies murine X-linked hypophosphatemia. J Clin Invest 118:722-734.

30.

Zhang

Dufau

(2003). Dual mechanisms of regulation of transcription of luteinizing hormone receptor gene by nuclear orphan receptors and histone deacetylase complexes. J Steroid Biochem Mol Biol 85:401-414.

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