Enhanced Expression of the Inorganic Phosphate Transporter Pit-1 Is Involved in BMP-2–Induced Matrix Mineralization in Osteoblast-Like Cells

Oxford University Press (OUP) - Tập 21 Số 5 - Trang 674-683 - 2006
Atsushi Suzuki1, Chafik Ghayor2, Jérôme Guicheux3, David Magne3, S. Quillard3, Ayako Kakita4, Yuka Ono1, Yoshitaka Miura4, Yutaka Oiso4, Mitsuyasu Itoh1, Joseph Caverzasio2
1Division of Endocrinology, Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Japan.
2Service of Bone Diseases, Department of Rehabilitation and Geriatrics, University Hospital of Geneva, Geneva, Switzerland
3INSERM EM 99-03, School of Dental Surgery, Nantes, France
4Department of Metabolic Diseases, Nagoya University Graduate School of Medicine, Nagoya, Japan

Tóm tắt

Abstract Pi handling by osteogenic cells is important for bone mineralization. The role of Pi transport in BMP-2–induced matrix calcification was studied. BMP-2 enhances Pit-1 Pi transporters in osteogenic cells. Experimental analysis suggest that this response is required for bone matrix calcification. Introduction: Bone morphogenetic proteins (BMPs) are produced by osteogenic cells and play an important role in bone formation. Inorganic phosphate (Pi) is a fundamental constituent of hydroxyapatite, and its transport by osteogenic cells is an important function for primary calcification of the bone matrix. In this study, we investigated the role of Pi transport in BMP-2–induced matrix mineralization. Materials and Methods: Confluent MC3T3-E1 osteoblast-like cells were exposed to BMP-2 for various time periods. Pi and alanine transport was determined using radiolabeled substrate, Pit-1 and Pit-2 expression by Northern blot analysis, cell differentiation by alkaline phosphatase activity, matrix mineralization by alizarin red staining, and the characteristics of mineral deposited in the matrix by transmission electron microscopy, electron diffraction analysis, and Fourier transformed infrared resolution (FTIR). Results: BMP-2 time- and dose-dependently stimulated Na-dependent Pi transport in MC3T3-E1 cells by increasing the Vmax of the transport system. This effect was preceded by an increase in mRNA encoding Pit-1 but not Pit-2. BMP-2 also dose-dependently enhanced extracellular matrix mineralization, an effect blunted by either phosphonoformic acid or expression of antisense Pit-1. Enhanced Pi transport and matrix mineralization induced by BMP-2 were blunted by a specific inhibitor of the c-Jun-N-terminal kinase (JNK) pathway. Conclusions: Results presented in this study indicate that, in addition to its well-known effect on several markers of the differentiation of osteoblastic cells, BMP-2 also stimulates Pi transport activity through a selective increase in expression of type III Pi transporters Pit-1. In MC3T3-E1 cells, this effect is mediated by the JNK pathway and plays an essential role in bone matrix calcification induced by BMP-2.

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Tài liệu tham khảo

Caverzasio, 1996, Characteristics and regulation of Pi transport in osteogenic cells for bone metabolism, Kidney Int, 49, 975, 10.1038/ki.1996.138

Caverzasio, 1996, Functional role of Pi transport in osteogenic cells, News Physiol Sci, 11, 119

Caverzasio, 1988, Characteristics of phosphate transport in osteoblastlike cells, Calcif Tissue Int, 43, 83, 10.1007/BF02555151

Montessuit, 1991, Characterization of a Pi transport system in cartilage matrix vesicles. Potential role in the calcification process, J Biol Chem, 266, 17791, 10.1016/S0021-9258(18)55196-6

Palmer, 1997, Expression of a newly identified phosphate transporter/retrovirus receptor in human SaOS-2 osteoblast-like cells and its regulation by insulin-like growth factor I, Endocrinology, 138, 5202, 10.1210/endo.138.12.5561

Palmer, 1999, In vivo expression of transcripts encoding the Glvr-1 phosphate transporter/retrovirus receptor during bone development, Bone, 24, 1, 10.1016/S8756-3282(98)00151-3

Giachelli, 2005, Regulation of vascular calcification: Roles of phosphate and osteopontin, Circ Res, 96, 717, 10.1161/01.RES.0000161997.24797.c0

Cecil, 2005, Role of interleukin-8 in PiT-1 expression and CXCR1-mediated inorganic phosphate uptake in chondrocytes, Arthritis Rheum, 52, 144, 10.1002/art.20748

Caverzasio, 2003, Biology & Diseases

Montessuit, 1994, Pi transport regulation by chicken growth plate chondrocytes, Am J Physiol, 267, E24

Selz, 1989, Regulation of Na-dependent Pi transport by parathyroid hormone in osteoblast-like cells, Am J Physiol, 256, E93

Zoidis, 2004, Regulation of phosphate (Pi) transport and NaPi-III transporter (Pit-1) mRNA in rat osteoblasts, J Endocrinol, 181, 531, 10.1677/joe.0.1810531

Suzuki, 2000, Stimulation of sodium-dependent phosphate transport and signaling mechanisms induced by basic fibroblast growth factor in MC3T3-E1 osteoblast-like cells, J Bone Miner Res, 15, 95, 10.1359/jbmr.2000.15.1.95

Schmitt, 1999, Bone morphogenetic proteins: An update on basic biology and clinical relevance, J Orthoped Res, 17, 269, 10.1002/jor.1100170217

Yamaguchi, 1995, Regulation of differentiation pathway of skeletal mesenchymal cells in cell lines by transforming growth factor-beta superfamily, Semin Cell Biol, 6, 165, 10.1006/scel.1995.0023

Hughes, 1995, The effects of bone morphogenetic protein-2, −4, and −6 on differentiation of rat osteoblast cells in vitro, Endocrinology, 136, 2671, 10.1210/endo.136.6.7750491

Hay, 1999, Effects of bone morphogenetic protein-2 on human neonatal calvaria cell differentiation, J Cell Biochem, 72, 81, 10.1002/(SICI)1097-4644(19990101)72:1<81::AID-JCB9>3.0.CO;2-N

Cheng, 2001, In vitro and in vivo induction of bone formation using a recombinant adenoviral vector carrying the human BMP-2 gene, Calcif Tissue Int, 68, 87, 10.1007/BF02678146

Zhen, 1997, Platelet-derived growth factor stimulates sodium-dependent Pi transport in osteoblastic cells via phospholipase Cgamma and phosphatidylinositol 3′ -kinase, J Bone Miner Res, 12, 36, 10.1359/jbmr.1997.12.1.36

Palmer, 2000, Transforming growth factor-beta stimulates inorganic phosphate transport and expression of the type III phosphate transporter Glvr-1 in chondrogenic ATDC5 cells, Endocrinology, 141, 2236, 10.1210/endo.141.6.7495

O'Hara, 1990, Characterization of a human gene conferring sensitivity to infection by gibbon ape leukemia virus, Cell Growth Differ, 1, 119

Miller, 1994, Cloning of the cellular receptor for amphotropic murine retroviruses reveals homology to that for gibbon ape leukemia virus, Proc Natl Acad Sci USA, 91, 78, 10.1073/pnas.91.1.78

Misell, 1987, Electron Diffraction: An Introduction for Biologists

Suzuki, 2002, Evidence for a role of p38 MAP kinase in expression of alkaline phosphatase during osteoblastic cell differentiation, Bone, 30, 91, 10.1016/S8756-3282(01)00660-3

Lowry, 1954, The quantitative histochemistry of brain. II. Enzyme measurements, J Biol Chem, 207, 19, 10.1016/S0021-9258(18)71242-8

Rey, 1995, Structural and chemical characteristics and maturation of the calcium-phosphate crystals formed during the calcification of the organic matrix synthesized by chicken osteoblasts in cell culture, J Bone Miner Res, 10, 1577, 10.1002/jbmr.5650101020

Loghman-Adham, 1987, Inhibition of Na+-Pi cotransporter in small gut brush border by phosphonocarboxylic acids, Am J Physiol, 252, G244

Wu, 2003, Effects of analogues of inorganic phosphate and sodium ion on mineralization of matrix vesicles isolated from growth plate cartilage of normal rapidly growing chickens, J Inorg Biochem, 94, 221, 10.1016/S0162-0134(03)00003-5

Gallea, 2001, Activation of mitogen-activated protein kinase cascades is involved in regulation of bone morphogenetic protein-2-induced osteoblast differentiation in pluripotent C2C12 cells, Bone, 28, 491, 10.1016/S8756-3282(01)00415-X

Guicheux, 2003, Activation of p38 mitogen-activated protein kinase and c-Jun-NH2-terminal kinase by BMP-2 and their implication in the stimulation of osteoblastic cell differentiation, J Bone Miner Res, 18, 2060, 10.1359/jbmr.2003.18.11.2060

Lemonnier, 2004, Protein kinase C-independent activation of protein kinase D is involved in BMP-2-induced activation of stress mitogen-activated protein kinases JNK and p38 and osteoblastic cell differentiation, J Biol Chem, 279, 259, 10.1074/jbc.M308665200

Hu, 2003, Activation of p38 mitogen-activated protein kinase is required for osteoblast differentiation, Endocrinology, 144, 2068, 10.1210/en.2002-220863

Werner, 1998, Na+-dependent phosphate cotransporters: The NaPi protein families, J Exp Biol, 201, 3135, 10.1242/jeb.201.23.3135

Anderson, 2005, The role of matrix vesicles in growth plate development and biomineralization, Front Biosci, 10, 822, 10.2741/1576

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Oxford University Press (OUP)

Tập 21 Số 5

674-683

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