Osteopontin.Org
Molecular SIBLINGs in Health and Disease

During normal human development, BSP is produced by osteoblasts, osteoclasts, osteocytes, and hypertrophic chondrocytes [1] and through its RGD sequence binds to the integrin, alphaVbeta3. OPN (also known as Secreted Phosphoprotein 1, 2ar, early T-lymphocyte activation 1, and transformation-associated phosphoprotein) is expressed in multiple tissue types and can bind to alphaVbeta3 [2-4] as well as CD44 [5, 6]. DMP1 expression has been found in teeth and bone [7, 8] and is similar to OPN in that it can interact with both alphaVbeta3 as well as CD44 [9]. OPN and BSP are also produced by trophoblasts [1, 10]. Dentin sialophosphoprotein (DSPP) has also been localized to the 4q21 region [7, 8, 11, 12] and its expression pattern has been primarily reported in teeth and bone [7, 11]. A fifth family member, termed MEPE for matrix extracellular phosphoglycoprotein, has been described which shares the RGD sequence motif, a casein kinase II phosphorylation site, common gene structure and maps to 4q21. The normal expression pattern is primarily in bone marrow with low level expression in lung, kidney and human placenta [13].

 

1.         Bianco P, Fisher LW, Young MF, Termine JD, Robey PG. Expression of bone sialoprotein (BSP) in developing human tissues. Calcif Tissue Int. 1991;49(6):421-6. PubMed PMID: 1818768.

2.         Wu Y, Denhardt DT, Rittling SR. Osteopontin is required for full expression of the transformed phenotype by the ras oncogene. Br J Cancer. 2000;83(2):156-63. PubMed PMID: 10901364.

3.         Takano S, Tsuboi K, Tomono Y, Mitsui Y, Nose T. Tissue factor, osteopontin, alphavbeta3 integrin expression in microvasculature of gliomas associated with vascular endothelial growth factor expression. Br J Cancer. 2000;82(12):1967-73. PubMed PMID: 10864205.

4.         Tuck AB, Elliott BE, Hota C, Tremblay E, Chambers AF. Osteopontin-induced, integrin-dependent migration of human mammary epithelial cells involves activation of the hepatocyte growth factor receptor (Met). J Cell Biochem. 2000;78(3):465-75. PubMed PMID: 10861844.

5.         Ue T, Yokozaki H, Kitadai Y, Yamamoto S, Yasui W, Ishikawa T, Tahara E. Co-expression of osteopontin and CD44v9 in gastric cancer. Int J Cancer. 1998;79(2):127-32. PubMed PMID: 9583725.

6.         Zohar R, Suzuki N, Suzuki K, Arora P, Glogauer M, McCulloch CA, Sodek J. Intracellular osteopontin is an integral component of the CD44-ERM complex involved in cell migration. J Cell Physiol. 2000;184(1):118-30. PubMed PMID: 10825241.

7.         MacDougall M, Gu TT, Simmons D. Dentin matrix protein-1, a candidate gene for dentinogenesis imperfecta. Connect Tissue Res. 1996;35(1-4):267-72.

8.         MacDougall M. Refined mapping of the human dentin sialophosphoprotein (DSPP) gene within the critical dentinogenesis imperfecta type II and dentin dysplasia type II loci. Eur J Oral Sci. 1998;106 Suppl 1:227-33.

9.         Jain A, Karadag A, Fohr B, Fisher LW, Fedarko NS. Three SIBLINGs (small integrin-binding ligand, N-linked glycoproteins) enhance factor H's cofactor activity enabling MCP-like cellular evasion of complement-mediated attack. J Biol Chem. 2002;277(16):13700-8. PubMed PMID: 11825898.

10.       Omigbodun A, Daiter E, Walinsky D, Fisher L, Young M, Hoyer J, Coutifaris C. Regulated expression of osteopontin in human trophoblasts. Ann N Y Acad Sci. 1995;760:346-9.

11.       D'Souza RN, Cavender A, Sunavala G, Alvarez J, Ohshima T, Kulkarni AB, MacDougall M. Gene expression patterns of murine dentin matrix protein 1 (Dmp1) and dentin sialophosphoprotein (DSPP) suggest distinct developmental functions in vivo. J Bone Miner Res. 1997;12(12):2040-9.

12.       Gu K, Chang S, Ritchie HH, Clarkson BH, Rutherford RB. Molecular cloning of a human dentin sialophosphoprotein gene. Eur J Oral Sci. 2000;108(1):35-42.

13.       Rowe PS, de Zoysa PA, Dong R, Wang HR, White KE, Econs MJ, Oudet CL. MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia. Genomics. 2000;67(1):54-68. PubMed PMID: 10945470.