Abstract
Bone matrix mineralisation plays a critical role in the determination of the overall biomechanical competence of bone. However, the molecular mechanisms of bone matrix mineralisation have not been fully elucidated. We used a proteomic approach to identify proteins and genes that may play a role in osteoblast matrix mineralisation. Proteomic differential display revealed a protein band that appeared only in mineralising mouse 7F2 osteoblasts. In-gel protein digestion and mass spectrometry proteomic analysis of this protein band identified 16 proteins. Furthermore, their corresponding transcripts were upregulated. This identification of proteins that may be associated with bone matrix mineralisation presents important new information toward a better understanding of the precise mechanisms of this process.
Similar content being viewed by others
References
Fratzl P, Gupta HS, Paschalis EP, Roschger P (2004) Structure and mechanical quality of the collagen-mineral nano-composite in bone. J Mater Chem 14:2115–2123
Buckwalter JA, Glimcher MJ, Cooper RR, Recker R (1995) Bone biology. Part I: structure, blood supply, cells, matrix, and mineralisation. J Bone Joint Surg 77-A:1256–1275
Glimcher MJ (1987) The nature of the mineral component of bone and the mechanism of calcification. In: Griffin PP (ed) AAOS Instr Course Lect XXXVI. AAOS Press, Park Ridge, IL, vol 36, pp 49–69
Stein GS, Lian JB, Stein JL, Van Wijnen AJ, Montecino M (1996) Transcriptional control of osteoblast growth and differentiation. Physiol Rev 76:593–629
Doi M, Nagano A, Nakamura Y (2002) Genome-wide screening by cDNA microarray of genes associated with matrix mineralisation by human mesenchymal stem cells in vitro. Biochem Biophys Res Commun 290:381–390
Borovecki F, Pecina-Slaus N, Vukicevic S (2007) Biological mechanisms of bone and cartilage remodelling–genomic perspective. Int Orthop 31(6):799–805
Lu P, Vogel C, Wang R, Yao X, Marcotte EM (2007) Absolute protein expression profiling estimates the relative contributions of transcriptional and translational regulation. Nat Biotechnol 25:117–124
Aguila HL, Rowe DW (2005) Skeletal development, bone remodeling, and hematopoiesis. J Bone Joint Surg 208:7–18
Hofstaetter JG, Saad FA, Samuel RE, Wunderlich L, Choi YH, Glimcher MJ (2004) Differential expression of VEGF isoforms and receptors in knee joint menisci under systemic hypoxia. Biochem Biophys Res Commun 324:667–672
Pfaffl MW, Horgan GW, Dempfle L (2002) Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30:e36
Lin P, Le-Niculescu H, Hofmeister R, McCaffery JM, Jin M, Hennemann H, McQuistan T, De Vries L, Farquhar MG (1998) The mammalian calcium-binding protein, nucleobindin (CALNUC), is a Golgi resident protein. J Cell Biol 141:1515–1527
Valencia CA, Cotten SW, Duan J, Liu R (2008) Modulation of nucleobindin-1 and nucleobindin-2 by caspases. FEBS Lett 582:286–290
Tsukumo Y, Tomida A, Kitahara O, Nakamura Y, Asada S, Mori K, Tsuruo T (2007) Nucleobindin 1 controls the unfolded protein response by inhibiting ATF6 activation. J Biol Chem 282:29264–29272
Schenk G, Duggleby RG, Nixon PF (1998) Properties and functions of the thiamin diphosphate dependent enzyme transketolase. Int J Biochem Cell Biol 30:1297–1318
Zhang AX, Yu WH, Ma BF, Yu XB, Mao FF, Liu W, Zhang JQ, Zhang XM, Li SN, Li MT, Lahn BT, Xiang AP (2007) Proteomic identification of differently expressed proteins responsible for osteoblast differentiation from human mesenchymal stem cells. Mol Cell Biochem 304:167–179
Cai L, Makhov AM, Bear JE (2007) F-actin binding is essential for coronin 1B function in vivo. J Cell Sci 120(Pt 10):1779–1790
Lucero HA, Lebeche D, Kaminer B (1998) ER calcistorin/protein-disulfide isomerase acts as a calcium storage protein in the endoplasmic reticulum of a living cell. Comparison with calreticulin and calsequestrin. J Biol Chem 273:9857–9863
Lahav J, Gofer-Dadosh N, Luboshitz J, Hess O, Shaklai M (2000) Protein disulfide isomerase mediates integrin-dependent adhesion. FEBS Lett 475:89–92
Beale EG, Harvey BJ, Forest C (2007) PCK1 and PCK2 as candidate diabetes and obesity genes. Cell Biochem Biophys 48:89–95
Modaressi S, Brechtel K, Christ B, Jungermann K (1998) Human mitochondrial phosphoenolpyruvate carboxykinase 2 gene. Structure, chromosomal localization and tissue-specific expression. Biochem J 333(Pt 2):359–366
Yeowell HN, Murad S, Pinnell SR (1991) Hydralazine differentially increases mRNAs for the alpha and beta subunits of prolyl 4-hydroxylase whereas it decreases pro alpha 1(I) collagen mRNAs in human skin fibroblasts. Arch Biochem Biophys 289:399–404
Nissi R, Böhling T, Autio-Harmainen H (2004) Immunofluorescence localization of prolyl 4-hydroxylase isoenzymes and type I and II collagens in bone tumours: type I enzyme predominates in osteosarcomas and chondrosarcomas, whereas type II enzyme predominates in their benign counterparts. Acta Histochem 106:111–121
Li Y, Chang Y, Zhang L, Feng Q, Liu Z, Zhang Y, Zuo J, Meng Y, Fang F (2005) High glucose upregulates pantothenate kinase 4 (PanK4) and thus affects M2-type pyruvate kinase (Pkm2). Mol Cell Biochem 277:117–125
Gururaj A, Barnes CJ, Vadlamudi RK, Kumar R (2004) Regulation of phosphoglucomutase 1 phosphorylation and activity by a signaling kinase. Oncogene 23:8118–8127
Plenz G, Gan Y, Raabe HM, Mueller PK (1993) Expression of vigilin in chicken cartilage and bone. Cell Tissue Res 273:381–389
Honda JY, Kobayashi I, Kiyoshima T, Yamaza H, Xie M, Takahashi K, Enoki N, Nagata K, Nakashima A, Sakai H (2008) Glycolytic enzyme Pgk1 is strongly expressed in the developing tooth germ of the mouse lower first molar. Histol Histopathol 23:423–432
Lee YN, Nechushtan H, Figov N, Razin E (2004) The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells. Immunity 20:145–151
Biswas C, Ostrovsky O, Makarewich CA, Wanderling S, Gidalevitz T, Argon Y (2007) The peptide-binding activity of GRP94 is regulated by calcium. Biochem J 405:233–241
Acknowledgments
The authors would like to thank Melvin Glimcher, Lila Graham and Patrick O’Neill for their critical reading of the manuscript and Marie Torres for her assistance in proteomic analysis. This work was supported by grants from The Peabody Foundation to Melvin J. Glimcher.
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Saad, F.A., Hofstaetter, J.G. Proteomic analysis of mineralising osteoblasts identifies novel genes related to bone matrix mineralisation. International Orthopaedics (SICOT) 35, 447–451 (2011). https://doi.org/10.1007/s00264-010-1076-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00264-010-1076-7