osteonectin

SPARC
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1BMO, 1NUB, 1SRA, 2V53
Identifiers
Aliases	SPARC, BM-40, ON, OI17, secreted protein acidic and cysteine rich
External IDs	OMIM: 182120 MGI: 98373 HomoloGene: 31132 GeneCards: 6678
Gene ontology
Molecular function	• calcium ion binding; • collagen binding; • extracellular matrix binding; • metal ion binding; • protein binding;
Cellular component	• cytoplasm; • platelet alpha granule; • endocytic vesicle lumen; • nuclear matrix; • proteinaceous extracellular matrix; • plasma membrane; • intracellular; • extracellular space; • extracellular region; • basement membrane; • cell surface; • platelet alpha granule membrane; • membrane-bounded vesicle; • mitochondrion; • platelet alpha granule lumen; • nucleus;
Biological process	• response to cytokine; • response to cadmium ion; • ossification; • lung development; • cellular response to growth factor stimulus; • response to peptide hormone; • platelet degranulation; • extracellular matrix organization; • blood coagulation; • response to L-ascorbic acid; • response to glucocorticoid; • wound healing; • receptor-mediated endocytosis; • negative regulation of endothelial cell proliferation; • positive regulation of endothelial cell migration; • platelet activation; • response to calcium ion; • response to gravity; • heart development; • response to lipopolysaccharide; • response to lead ion; • regulation of cell proliferation; • negative regulation of angiogenesis; • inner ear development; • regulation of cell morphogenesis; • response to cAMP; • response to ethanol; • bone development; • signal transduction;
	Sources:Amigo / QuickGO
RNA expression pattern
	; ;
	More reference expression data
Orthologs
	6678
	20692
	ENSG00000113140
	ENSMUSG00000018593
	P09486
	P07214
	NM_003118; NM_001309443; NM_001309444
	NM_009242; NM_001290817
	NP_003109.1; NP_001296372.1; NP_001296373.1
	NP_033268.1
	Wikidata
View/Edit Human	View/Edit Mouse

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/07/06 11:42:47」(JST)

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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

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

Structure

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

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

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 to 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

*Sparc* knockout mouse phenotype
Characteristic	Phenotype
Homozygote viability	Normal
Homozygous Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Abnormal^[6]
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Abnormal^[7]
Radiography	Abnormal^[8]
Body temperature	Normal
Eye morphology	Abnormal^[9]
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Brain histopathology	Normal
Eye Histopathology	Abnormal
MicroCT & Quantitative Faxitron	Abnormal
Salmonella infection	Normal^[10]
Citrobacter infection	Normal^[11]
All tests and analysis from^[12]^[13]

Model organisms have been used in the study of SPARC function. A conditional knockout mouse line, called Sparc^{tm1a(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

^ Villarreal XC, Mann KG, Long GL (Jul 1989). "Structure of human osteonectin based upon analysis of cDNA and genomic sequences". Biochemistry 28 (15): 6483–91. doi:10.1021/bi00441a049. PMID 2790009.
^ Guweidhi A, Kleeff J, Adwan H, Giese NA, Wente MN, Giese T, Büchler MW, Berger MR, Friess H (Aug 2005). "Osteonectin influences growth and invasion of pancreatic cancer cells". Annals of Surgery 242 (2): 224–34. doi:10.1097/01.sla.0000171866.45848.68. PMC 1357728. PMID 16041213.
^ Wasi S, Otsuka K, Yao KL, Tung PS, Aubin JE, Sodek J, Termine JD (Jun 1984). "An osteonectinlike protein in porcine periodontal ligament and its synthesis by periodontal ligament fibroblasts". Canadian Journal of Biochemistry and Cell Biology 62 (6): 470–8. doi:10.1139/o84-064. PMID 6380686.
^ Young MF, Kerr JM, Ibaraki K, Heegaard AM, Robey PG (Aug 1992). "Structure, expression, and regulation of the major noncollagenous matrix proteins of bone". Clinical Orthopaedics and Related Research (281): 275–94. doi:10.1097/00003086-199208000-00042. PMID 1499220.
^ Lane TF, Sage EH (Feb 1994). "The biology of SPARC, a protein that modulates cell-matrix interactions". FASEB Journal 8 (2): 163–73. PMID 8119487.
^ "Dysmorphology data for Sparc". Wellcome Trust Sanger Institute.
^ "DEXA data for Sparc". Wellcome Trust Sanger Institute.
^ "Radiography data for Sparc". Wellcome Trust Sanger Institute.
^ "Eye morphology data for Sparc". Wellcome Trust Sanger Institute.
^ "Salmonella infection data for Sparc". Wellcome Trust Sanger Institute.
^ "Citrobacter infection data for Sparc". Wellcome Trust Sanger Institute.
^ ^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.
^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
^ "International Knockout Mouse Consortium".
^ "Mouse Genome Informatics".
^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

External links

Osteonectin at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. Biology of vascular calcification in chronic kidney disease
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English Journal

Osteoblastic differentiation of stem cells from human exfoliated deciduous teeth induced by thermosensitive hydrogels with strontium phosphate.

Su WT1, Chou WL2, Chou CM3.
Materials science & engineering. C, Materials for biological applications.Mater Sci Eng C Mater Biol Appl.2015 Jul 1;52:46-53. doi: 10.1016/j.msec.2015.03.025. Epub 2015 Mar 24.
Stem cells from human exfoliated deciduous teeth (SHEDs) are a novel source of multi-potential stem cells for tissue engineering because of their potential to differentiate into multiple cell lineages. Strontium exhibits an important function in bone remodeling because it can simulate bone formation
PMID 25953539

Osteogenic cell fractions isolated from mouse tongue muscle.

Harada K1, Harada T1, Ferdous T1, Takenawa T1, Ueyama Y1.
Molecular medicine reports.Mol Med Rep.2015 Jul;12(1):31-6. doi: 10.3892/mmr.2015.3350. Epub 2015 Feb 13.
The use of stem cells represents a promising approach for the treatment of bone defects. However, successful treatments rely upon the availability of cells that are easily obtained and that appropriately differentiate into osteoblasts. The tongue potentially represents a source of autologous cells f
PMID 25684092

Effect of Oxidized Low Density Lipoprotein on the Expression of Runx2 and SPARC Genes in Vascular Smooth Muscle Cells.

Farrokhi E1, Ghatreh Samani K2, Hashemzadeh Chaleshtori M3, Tabatabaiefar MA4.
Iranian biomedical journal.Iran Biomed J.2015 May 30.Pii-IBJ-A-10-1308-1. [Epub ahead of print]
BACKGROUND: Vascular calcification is an important stage in atherosclerosis. During this stage, vascular smooth muscle cells (VSMC) synthesize many osteogenic factors such as osteonectin (encoded by SPARC). Oxidative stress plays a critical role in atherosclerosis progression, and its accumulation i
PMID 26025968

Japanese Journal

Behavioral Signs of Chronic Back Pain in the SPARC-Null Mouse

MILLECAMPS Magali,TAJERIAN Maral,HELENE SAGE E.,STONE Laura S.
Spine 36(2), 95-102, 2011-01-15
NAID 10027964355

半導体レーザー照射後のラット臼歯における非コラーゲンタンパクの遺伝子発現

重谷佳見,大倉直人,吉羽邦彦,吉羽永子,大島勇人,興地隆史
日本歯科保存学雑誌 53(5), 495-501, 2010-10-31
… ーザー装置(オサダライトサージ3000)を用いて,出力1.5W,60秒3回の条件でレーザー照射を行った.なお,非照射の上顎臼歯を対照とした.照射1,3,7日後に抜歯を行い,歯冠部よりmRNAを抽出した後,RT-PCR法にてosteopontin,osteonectin,osteocalcin,dentin sialophosphoprotein,dentin matrix protein 1,およびbone sialoproteinのmRNA発現解析を行った.また,歯髄の反応を組織学的に観察した.その結果,すべてのタンパクのmRNA発現が3日後までに増加を示すとともに,こ …
NAID 110008006920

Related Pictures

[pmid2790009-1] Villarreal XC, Mann KG, Long GL (Jul 1989). "Structure of human osteonectin based upon analysis of cDNA and genomic sequences". Biochemistry 28 (15): 6483–91. doi:10.1021/bi00441a049. PMID 2790009.

[pmid16041213-2] Guweidhi A, Kleeff J, Adwan H, Giese NA, Wente MN, Giese T, Büchler MW, Berger MR, Friess H (Aug 2005). "Osteonectin influences growth and invasion of pancreatic cancer cells". Annals of Surgery 242 (2): 224–34. doi:10.1097/01.sla.0000171866.45848.68. PMC 1357728. PMID 16041213.

[pmid6380686-3] Wasi S, Otsuka K, Yao KL, Tung PS, Aubin JE, Sodek J, Termine JD (Jun 1984). "An osteonectinlike protein in porcine periodontal ligament and its synthesis by periodontal ligament fibroblasts". Canadian Journal of Biochemistry and Cell Biology 62 (6): 470–8. doi:10.1139/o84-064. PMID 6380686.

[pmid1499220-4] Young MF, Kerr JM, Ibaraki K, Heegaard AM, Robey PG (Aug 1992). "Structure, expression, and regulation of the major noncollagenous matrix proteins of bone". Clinical Orthopaedics and Related Research (281): 275–94. doi:10.1097/00003086-199208000-00042. PMID 1499220.

[pmid8119487-5] Lane TF, Sage EH (Feb 1994). "The biology of SPARC, a protein that modulates cell-matrix interactions". FASEB Journal 8 (2): 163–73. PMID 8119487.

[Dysmorphology-6] "Dysmorphology data for Sparc". Wellcome Trust Sanger Institute.

[DEXA-7] "DEXA data for Sparc". Wellcome Trust Sanger Institute.

[Radiography-8] "Radiography data for Sparc". Wellcome Trust Sanger Institute.

[Eye_morphology-9] "Eye morphology data for Sparc". Wellcome Trust Sanger Institute.

[.27.27Salmonella.27.27_infection-10] "Salmonella infection data for Sparc". Wellcome Trust Sanger Institute.

[.27.27Citrobacter.27.27_infection-11] "Citrobacter infection data for Sparc". Wellcome Trust Sanger Institute.

[mgp_reference-12] 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.

[allele_ref-14] "International Knockout Mouse Consortium".

[mgi_allele_ref-15] "Mouse Genome Informatics".

[pmid21677750-16] Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.

[mouse_library-17] Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-18] Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.

[pmid21722353-19] van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

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