Osteonectin

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Secreted protein, acidic, cysteine-rich (osteonectin)
Protein SPARC PDB 1bmo.png
PDB rendering based on 1bmo.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols SPARC ; ON
External IDs OMIM182120 MGI98373 HomoloGene31132 GeneCards: SPARC Gene
RNA expression pattern
PBB GE SPARC 200665 s at tn.png
PBB GE SPARC 212667 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 6678 20692
Ensembl ENSG00000113140 ENSMUSG00000018593
UniProt P09486 P07214
RefSeq (mRNA) NM_003118 NM_009242
RefSeq (protein) NP_003109 NP_033268
Location (UCSC) Chr 5:
151.04 – 151.07 Mb
Chr 11:
55.39 – 55.42 Mb
PubMed search [1] [2]
Not to be confused with Osteocalcin or Osteopontin.

Osteonectin (ON) also known as secreted protein acidic and rich in cysteine (SPARC) or basement-membrane protein 40 (BM-40) is a protein that in humans is encoded by the SPARC gene.

Osteonectin is a glycoprotein in the bone that binds calcium. It is secreted by osteoblasts during bone formation, initiating mineralization and promoting mineral crystal formation. Osteonectin also shows affinity for collagen in addition to bone mineral calcium. A correlation between osteonectin over-expression and ampullary cancers and chronic pancreatitis has been found.

Gene[edit]

The human SPARC gene is 26.5 kb long, and contains 10 exons and 9 introns and is located on chromosome 5q31-q33.

Structure[edit]

Osteonectin is a 40 kD acidic and cysteine-rich glycoprotein consisting of a single polypeptide chain that can be broken into 4 domains: 1) a Ca++ binding domain near the glutamic acid-rich region at the amino terminus (domain I), 2) a cysteine-rich domain (II), 3) a hydrophilic region (domain III), and 4) an EF hand motif at the carboxy terminus region (domain IV).[1]

Function[edit]

Osteonectin is an acidic extracellular matrix glycoprotein that plays a vital role in bone mineralization, cell-matrix interactions, and collagen binding. Osteonectin also increases the production and activity of matrix metalloproteinases, a function important to invading cancer cells within bone. Additional functions of osteonectin beneficial to tumor cells include angiogenesis, proliferation and migration. Overexpression of osteonectin is reported in many human cancers such as breast, prostate and colon.[2]

This molecule has been implicated in several biological functions, including mineralization of bone and cartilage, inhibiting mineralization, modulation of cell proliferation, facilitation of acquisition of differentiated phenotype and promotion of cell attachment and spreading.

A number of phosphoproteins and glycoproteins are found in bone. The phosphate is bound to the protein backbone through phosphorylated serine or threonine amino acid residues. The best characterized of these bone proteins is osteonectin. It binds collagen and hydroxyapatite in separate domains, is found in relatively large amounts in immature bone, and promotes mineralization of collagen.

Tissue distribution[edit]

Fibroblasts, including periodontal fibroblasts, synthesize osteonectin.[3] This protein is synthesized by macrophages at sites of wound repair and platelet degranulation, so it may play an important role in wound healing. SPARC does not support cell attachment, and like thrombospondin and tenascin, is anti-adhesive and an inhibitor of cell spreading. It disrupts focal adhesions in fibroblasts. It also regulates the proliferation of some cells, especially endothelial cells, mediated by its ability to bind to cytokines and growth factors.[4] Osteonectin has also been found decrease DNA synthesis in cultured bone.[5]

High levels of immunodetectable osteonectin are found in active osteoblasts and marrow progenitor cells, odontoblasts, periodontal ligament and gingival cells, and some chondrocytes and hypertrophic chondrocytes. Osteonectin is also detectable in osteoid, bone matrix proper, and dentin. Osteonectin has been localized in a variety of tissues, but is found in greatest abundance in osseous tissue, tissues characterized by high turnover (such as intestinal epithelium), basement membranes, and certain neoplasms. Osteonectin is expressed by a wide variety of cells, including chondrocytes, fibroblasts, platelets, endothelial cells, epithelial cells, Leydig cells, Sertoli cells, luteal cells, adrenal cortical cells, and numerous neoplastic cell lines (such as SaOS-2 cells from human osteosarcoma).

Model organisms[edit]

Model organisms have been used in the study of SPARC function. A conditional knockout mouse line, called Sparctm1a(EUCOMM)Wtsi[14][15] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty six tests were carried out on mutant mice and six significant abnormalities were observed.[12] Homozygous mutant animals had unusually white incisors, decreased bone mineral density, abnormal lens morphology, cataracts and a decreased length of long bones.[12]

References[edit]

  1. ^ Villarreal XC, Mann KG, Long GL (July 1989). "Structure of human osteonectin based upon analysis of cDNA and genomic sequences". Biochemistry 28 (15): 6483–91. doi:10.1021/bi00441a049. PMID 2790009. 
  2. ^ Guweidhi A, Kleeff J, Adwan H, Giese NA, Wente MN, Giese T, Büchler MW, Berger MR, Friess H (August 2005). "Osteonectin influences growth and invasion of pancreatic cancer cells". Ann. Surg. 242 (2): 224–234. doi:10.1097/01.sla.0000171866.45848.68. PMC 1357728. PMID 16041213. 
  3. ^ Wasi S, Otsuka K, Yao KL, Tung PS, Aubin JE, Sodek J, Termine JD (June 1984). "An osteonectinlike protein in porcine periodontal ligament and its synthesis by periodontal ligament fibroblasts". Can. J. Biochem. Cell Biol. 62 (6): 470–8. doi:10.1139/o84-064. PMID 6380686. 
  4. ^ Young MF, Kerr JM, Ibaraki K, Heegaard AM, Robey PG (August 1992). "Structure, expression, and regulation of the major noncollagenous matrix proteins of bone". Clin. Orthop. Relat. Res. (281): 275–94. PMID 1499220. 
  5. ^ Lane TF, Sage EH (February 1994). "The biology of SPARC, a protein that modulates cell-matrix interactions". FASEB J. 8 (2): 163–73. PMID 8119487. 
  6. ^ "Dysmorphology data for Sparc". Wellcome Trust Sanger Institute. 
  7. ^ "DEXA data for Sparc". Wellcome Trust Sanger Institute. 
  8. ^ "Radiography data for Sparc". Wellcome Trust Sanger Institute. 
  9. ^ "Eye morphology data for Sparc". Wellcome Trust Sanger Institute. 
  10. ^ "Salmonella infection data for Sparc". Wellcome Trust Sanger Institute. 
  11. ^ "Citrobacter infection data for Sparc". Wellcome Trust Sanger Institute. 
  12. ^ a b c d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. 
  13. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  14. ^ "International Knockout Mouse Consortium". 
  15. ^ "Mouse Genome Informatics". 
  16. ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.  edit
  17. ^ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  18. ^ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  19. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 

Further reading[edit]

External links[edit]