Summary: Non-collagenous, calcium-binding glycoprotein of developing bone. It links collagen to mineral in the bone matrix. In the synonym SPARC glycoprotein, the acronym stands for Secreted Protein, Acidic and Rich in Cysteine.

Top Publications

  1. Kapinas K, Kessler C, Delany A. miR-29 suppression of osteonectin in osteoblasts: regulation during differentiation and by canonical Wnt signaling. J Cell Biochem. 2009;108:216-24 pubmed publisher
    The matricellular protein osteonectin, secreted protein acidic and rich in cysteine (SPARC, BM-40), is the most abundant non-collagenous matrix protein in bone...
  2. Golembieski W, Thomas S, Schultz C, Yunker C, McClung H, Lemke N, et al. HSP27 mediates SPARC-induced changes in glioma morphology, migration, and invasion. Glia. 2008;56:1061-75 pubmed publisher
    ..As such, it is a potential therapeutic target to inhibit SPARC-induced glioma invasion. ..
  3. Llera A, Girotti M, Benedetti L, Podhajcer O. Matricellular proteins and inflammatory cells: a task force to promote or defeat cancer?. Cytokine Growth Factor Rev. 2010;21:67-76 pubmed publisher
    ..In this review we discuss the evidence available up to date that relates matricellular proteins with the regulation of the inflammatory response and tumor progression. ..
  4. Kos K, Wilding J. SPARC: a key player in the pathologies associated with obesity and diabetes. Nat Rev Endocrinol. 2010;6:225-35 pubmed publisher
    SPARC (secreted protein acidic and rich in cysteine, also known as osteonectin or BM-40) is a widely expressed profibrotic protein with pleiotropic roles, which have been studied in a variety of conditions...
  5. Schellings M, Vanhoutte D, Swinnen M, Cleutjens J, Debets J, van Leeuwen R, et al. Absence of SPARC results in increased cardiac rupture and dysfunction after acute myocardial infarction. J Exp Med. 2009;206:113-23 pubmed publisher
    The matricellular protein SPARC (secreted protein, acidic and rich in cysteine, also known as osteonectin) mediates cell-matrix interactions during wound healing and regulates the production and/or assembly of the extracellular matrix (..
  6. Bhoopathi P, Chetty C, Gujrati M, Dinh D, Rao J, Lakka S. The role of MMP-9 in the anti-angiogenic effect of secreted protein acidic and rich in cysteine. Br J Cancer. 2010;102:530-40 pubmed publisher
    ..Overexpression of SPARC decreases angiogenesis, which leads to decreased tumour growth. Further, the role of MMP-9 could be attributed to the anti-angiogenic effect of SPARC. ..
  7. Horie K, Tsuchihara M, Nakatsura T. Silencing of secreted protein acidic and rich in cysteine inhibits the growth of human melanoma cells with G arrest induction. Cancer Sci. 2010;101:913-9 pubmed publisher
    ..Our findings suggest that SPARC contributes to cell growth and could be a potential target molecule for melanoma therapy. ..
  8. Wong S, Crowley D, Bronson R, Hynes R. Analyses of the role of endogenous SPARC in mouse models of prostate and breast cancer. Clin Exp Metastasis. 2008;25:109-18 pubmed
    Secreted protein, acidic and rich in cysteine (SPARC, also known as osteonectin or BM-40) is a glycoprotein component of the extracellular matrix that has been reported to be involved with a variety of cellular processes...
  9. Nagai M, Gerhard R, Fregnani J, Nonogaki S, Rierger R, Netto M, et al. Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients. Breast Cancer Res Treat. 2011;126:1-14 pubmed publisher
    ..These data indicate that NDRG1 over-expression and SPARC down-regulation could play important roles in breast cancer progression and serve as useful biomarkers to better define breast cancer prognosis. ..

More Information


  1. Zhivkova Galunska M, Adwan H, Eyol E, Kleeff J, Kolb A, Bergmann F, et al. Osteopontin but not osteonectin favors the metastatic growth of pancreatic cancer cell lines. Cancer Biol Ther. 2010;10:54-64 pubmed
    ..b>Osteonectin and osteopontin, two proteins of the extracellular matrix, have been found to be upregulated in PDAC...
  2. Millecamps M, Tajerian M, Sage E, Stone L. Behavioral signs of chronic back pain in the SPARC-null mouse. Spine (Phila Pa 1976). 2011;36:95-102 pubmed publisher
    ..We hypothesize that the SPARC-null mouse is useful as a model of chronic back pain due to degenerative disc disease. ..
  3. Nagaraju G, Sharma D. Anti-cancer role of SPARC, an inhibitor of adipogenesis. Cancer Treat Rev. 2011;37:559-66 pubmed publisher
    ..This review focuses on the anti-cancer role of SPARC as it pertains to obesity. ..
  4. Yang E, Kang H, Koh K, Rhee H, Kim N, Kim H. Frequent inactivation of SPARC by promoter hypermethylation in colon cancers. Int J Cancer. 2007;121:567-75 pubmed
    ..79% vs. 75.83% 5-year survival rate, p = 0.0014). The results indicate that epigenetic gene silencing of SPARC is frequent in colon cancers, and that inactivation of SPARC is related to rapid progression of colon cancers. ..
  5. McClung H, Thomas S, Osenkowski P, Toth M, Menon P, Raz A, et al. SPARC upregulates MT1-MMP expression, MMP-2 activation, and the secretion and cleavage of galectin-3 in U87MG glioma cells. Neurosci Lett. 2007;419:172-7 pubmed
    ..Our results suggest that their upregulation and activation may be a consequence of increased SPARC expression. These data provide a provisional mechanism whereby SPARC contributes to brain tumor invasion. ..
  6. Nie J, Bradshaw A, Delany A, Sage E. Inactivation of SPARC enhances high-fat diet-induced obesity in mice. Connect Tissue Res. 2011;52:99-108 pubmed publisher
    ..In the absence of SPARC, mice show enhanced DIO. In adult animals, SPARC functions in the production and remodeling of adipose tissue, as well as in the regulation of preadipocyte differentiation. ..
  7. Bradshaw A, Baicu C, Rentz T, Van Laer A, Bonnema D, Zile M. Age-dependent alterations in fibrillar collagen content and myocardial diastolic function: role of SPARC in post-synthetic procollagen processing. Am J Physiol Heart Circ Physiol. 2010;298:H614-22 pubmed publisher
    ..These data support the hypothesis that SPARC plays a key role in post-synthetic procollagen processing and contributes to the increase in collagen content found in the aged myocardium. ..
  8. Atorrasagasti C, Malvicini M, Aquino J, Alaniz L, Garcia M, Bolontrade M, et al. Overexpression of SPARC obliterates the in vivo tumorigenicity of human hepatocellular carcinoma cells. Int J Cancer. 2010;126:2726-40 pubmed publisher
    ..These evidences point to SPARC as a novel target for HCC treatment. ..
  9. Zhang J, Zhang Q, Zhang Q, Liu X, Li C, Guo Z. Expression and clinical significance of SPARC in clinical stage II tongue squamous cell carcinoma. Ai Zheng. 2009;28:68-71 pubmed
    ..46, p < 0.001) and recurrence (r < 0.595, p < 0.001). SPARC is highly expressed in stage II tongue squamous cell carcinoma, and positively correlated to survival, occult lymph node metastasis and recurrence. ..
  10. Hartmann U, Hülsmann H, Seul J, Röll S, Midani H, Breloy I, et al. Testican-3: a brain-specific proteoglycan member of the BM-40/SPARC/osteonectin family. J Neurochem. 2013;125:399-409 pubmed publisher
    ..of secreted proteoglycans structurally related to the BM-40/secreted protein acidic and rich in cystein (SPARC) osteonectin family of extracellular calcium-binding proteins...
  11. Machado do Reis L, Kessler C, Adams D, Lorenzo J, Jorgetti V, Delany A. Accentuated osteoclastic response to parathyroid hormone undermines bone mass acquisition in osteonectin-null mice. Bone. 2008;43:264-73 pubmed publisher
    ..proteins play a unique role in the skeleton as regulators of bone remodeling, and the matricellular protein osteonectin (SPARC, BM-40) is the most abundant non-collagenous protein in bone...
  12. Pellagatti A, Jadersten M, Forsblom A, Cattan H, Christensson B, Emanuelsson E, et al. Lenalidomide inhibits the malignant clone and up-regulates the SPARC gene mapping to the commonly deleted region in 5q- syndrome patients. Proc Natl Acad Sci U S A. 2007;104:11406-11 pubmed
    ..SPARC may play a role in the pathogenesis of the 5q- syndrome. ..
  13. Rotllant J, Liu D, Yan Y, Postlethwait J, Westerfield M, Du S. Sparc (Osteonectin) functions in morphogenesis of the pharyngeal skeleton and inner ear. Matrix Biol. 2008;27:561-72 pubmed publisher
    Sparc (Osteonectin), a matricellular glycoprotein expressed by many differentiated cells, is a major non-collagenous constituent of vertebrate bones...
  14. Bhoopathi P, Gondi C, Gujrati M, Dinh D, Lakka S. SPARC mediates Src-induced disruption of actin cytoskeleton via inactivation of small GTPases Rho-Rac-Cdc42. Cell Signal. 2011;23:1978-87 pubmed publisher
    ..Taken together, these results establish SPARC as an effector of Src-induced cytoskeleton disruption in Daoy medulloblastoma cells, which subsequently led to decreased migration and invasion. ..
  15. Rivera L, Brekken R. SPARC promotes pericyte recruitment via inhibition of endoglin-dependent TGF-?1 activity. J Cell Biol. 2011;193:1305-19 pubmed publisher
    ..These results demonstrate that SPARC promotes pericyte migration by diminishing TGF-? activity and identify a novel function for endoglin in controlling pericyte behavior. ..
  16. Abouzeid H, Boisset G, Favez T, Youssef M, Marzouk I, Shakankiry N, et al. Mutations in the SPARC-related modular calcium-binding protein 1 gene, SMOC1, cause waardenburg anophthalmia syndrome. Am J Hum Genet. 2011;88:92-8 pubmed publisher
    ..Knockdown experiments of the zebrafish smoc1 revealed that smoc1 is important in eye development and that it is expressed in many organs, including brain and somites. ..
  17. Smit D, Gardiner B, Sturm R. Osteonectin downregulates E-cadherin, induces osteopontin and focal adhesion kinase activity stimulating an invasive melanoma phenotype. Int J Cancer. 2007;121:2653-60 pubmed
    b>Osteonectin is recognised as a marker of metastasis progression in melanoma and has been implicated in the transition from radial to vertical growth phase...
  18. Bozkurt S, Ayan E, Bolukbasi F, Elmaci I, Pamir N, Sav A. Immunohistochemical expression of SPARC is correlated with recurrence, survival and malignant potential in meningiomas. APMIS. 2009;117:651-9 pubmed publisher
    ..SPARC (secreted protein, acidic and rich in cysteine) (osteonectin) is a matricellular glycoprotein that regulates cell function by interacting with different extracellular ..
  19. Nie J, Sage E. SPARC inhibits adipogenesis by its enhancement of beta-catenin signaling. J Biol Chem. 2009;284:1279-90 pubmed publisher
    ..These findings demonstrate a role for SPARC in adipocyte morphogenesis and in signaling processes leading to terminal differentiation. ..
  20. Sage E. Purification of SPARC/osteonectin. Curr Protoc Cell Biol. 2003;Chapter 10:Unit 10.11 pubmed publisher
    ..This unit describes the purification of SPARC, also termed osteonectin and BM/40, from cultured mammalian cells...
  21. Seet L, Su R, Barathi V, Lee W, Poh R, Heng Y, et al. SPARC deficiency results in improved surgical survival in a novel mouse model of glaucoma filtration surgery. PLoS ONE. 2010;5:e9415 pubmed publisher
    ..The evidence presented in this report is strongly supportive for the targeting of SPARC to increase the success of glaucoma filtration surgery. ..
  22. Haber C, Gottifredi V, Llera A, Salvatierra E, Prada F, Alonso L, et al. SPARC modulates the proliferation of stromal but not melanoma cells unless endogenous SPARC expression is downregulated. Int J Cancer. 2008;122:1465-75 pubmed
    ..Thus, malignant cells expressing or not expressing SPARC developed alternative mechanisms that, in contrary to stromal cells, rendered them SPARC-insensitive. ..
  23. Gotoh N, Perdue N, Matsushima H, Sage E, Yan Q, Clark J. An in vitro model of posterior capsular opacity: SPARC and TGF-beta2 minimize epithelial-to-mesenchymal transition in lens epithelium. Invest Ophthalmol Vis Sci. 2007;48:4679-87 pubmed
    ..The results indicate a functional intersection between pathways activated by TGF-beta2 and SPARC in the formation of PCO. ..
  24. Chlenski A, Guerrero L, Peddinti R, Spitz J, Leonhardt P, Yang Q, et al. Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors. Mol Cancer. 2010;9:138 pubmed publisher
    ..Its simple structure and ease of production indicate that it may have clinical utility in the treatment of high-risk neuroblastoma and other types of pediatric and adult cancers, which depend on angiogenesis. ..
  25. Socha M, Manhiani M, Said N, Imig J, Motamed K. Secreted protein acidic and rich in cysteine deficiency ameliorates renal inflammation and fibrosis in angiotensin hypertension. Am J Pathol. 2007;171:1104-12 pubmed
    ..These results identify SPARC as an effector of ANG II signaling and suggest an important role for SPARC in mediating ANG II-induced oxidative stress, inflammation, and fibrosis. ..
  26. Fenouille N, Puissant A, Tichet M, Zimniak G, Abbe P, Mallavialle A, et al. SPARC functions as an anti-stress factor by inactivating p53 through Akt-mediated MDM2 phosphorylation to promote melanoma cell survival. Oncogene. 2011;30:4887-900 pubmed publisher
    Aberrant expression of Secreted Protein Acidic and Rich in Cysteine (SPARC)/osteonectin has been associated with an invasive tumor cell phenotype and poor outcome in human melanomas...
  27. Podhajcer O, Benedetti L, Girotti M, Prada F, Salvatierra E, Llera A. The role of the matricellular protein SPARC in the dynamic interaction between the tumor and the host. Cancer Metastasis Rev. 2008;27:523-37 pubmed publisher
    ..Its relevance as a potential target in cancer therapy is also discussed. ..
  28. Chlenski A, Cohn S. Modulation of matrix remodeling by SPARC in neoplastic progression. Semin Cell Dev Biol. 2010;21:55-65 pubmed publisher
    ..Understanding the mechanism of matrix remodeling and its regulation by SPARC is essential for the development of new treatment strategies for highly aggressive cancers. ..
  29. Zhao Z, Wang Y, Chu Y, Ye Z, Tao H. SPARC is associated with gastric cancer progression and poor survival of patients. Clin Cancer Res. 2010;16:260-8 pubmed publisher
    ..SPARC, intergrin beta1, and MMP-2 protein could be useful markers to predict tumor progression. ..
  30. Rentz T, Poobalarahi F, Bornstein P, Sage E, Bradshaw A. SPARC regulates processing of procollagen I and collagen fibrillogenesis in dermal fibroblasts. J Biol Chem. 2007;282:22062-71 pubmed
    ..We conclude that SPARC mediates the association of procollagen I with cells, as well as its processing and incorporation into the extracellular matrix. ..
  31. Seno T, Harada H, Kohno S, Teraoka M, Inoue A, Ohnishi T. Downregulation of SPARC expression inhibits cell migration and invasion in malignant gliomas. Int J Oncol. 2009;34:707-15 pubmed
    ..These results suggest that SPARC plays an essential role in the invasive activity of human glioma cells, under hypoxic conditions. Downregulation of SPARC may be a novel anti-invasion therapeutic strategy for malignant gliomas. ..
  32. Huynh M, Zhu S, Kollara A, Brown T, Winklbauer R, Ringuette M. Knockdown of SPARC leads to decreased cell-cell adhesion and lens cataracts during post-gastrula development in Xenopus laevis. Dev Genes Evol. 2011;220:315-27 pubmed publisher
    ..The combined data suggest a critical requirement for SPARC during post-gastrula development in Xenopus embryos and that SPARC, directly or indirectly, promotes cell-cell adhesion in vivo...
  33. Reding T, Wagner U, Silva A, Sun L, Bain M, Kim S, et al. Inflammation-dependent expression of SPARC during development of chronic pancreatitis in WBN/Kob rats and a microarray gene expression analysis. Physiol Genomics. 2009;38:196-204 pubmed publisher
    ..Inflammation dependent expression of SPARC appears to be lost during acinar-to-duct metaplasia both in rat and human pancreas. ..
  34. Ma C, Palmer A, Taylor J. Synergistic effects of osteonectin and NGF in promoting survival and neurite outgrowth of superior cervical ganglion neurons. Brain Res. 2009;1289:1-13 pubmed publisher
    ..Here we examined the effects of osteonectin (ON), a major factor secreted by SCs, on survival and neuritogenesis of mouse superior cervical ganglion (SCG) ..
  35. Derosa C, Furusato B, Shaheduzzaman S, Srikantan V, Wang Z, Chen Y, et al. Elevated osteonectin/SPARC expression in primary prostate cancer predicts metastatic progression. Prostate Cancer Prostatic Dis. 2012;15:150-6 pubmed publisher
    ..0006, AUC=0.803). In summary, we propose that evaluation of SPARC in primary CaP has potential as a prognostic marker of metastatic progression. ..
  36. Atorrasagasti C, Peixoto E, Aquino J, Kippes N, Malvicini M, Alaniz L, et al. Lack of the matricellular protein SPARC (secreted protein, acidic and rich in cysteine) attenuates liver fibrogenesis in mice. PLoS ONE. 2013;8:e54962 pubmed publisher
    ..Overall our data suggest that SPARC plays a significant role in liver fibrogenesis. Interventions to inhibit SPARC expression are suggested as promising approaches for liver fibrosis treatment. ..
  37. Bergamaschi A, Tagliabue E, Sørlie T, Naume B, Triulzi T, Orlandi R, et al. Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome. J Pathol. 2008;214:357-67 pubmed
  38. Hsiao Y, Lien H, Hwa H, Kuo W, Chang K, Hsieh F. SPARC (osteonectin) in breast tumors of different histologic types and its role in the outcome of invasive ductal carcinoma. Breast J. 2010;16:305-8 pubmed publisher
    ..Secreted protein acidic and rich in cystein may be useful as a prognostic indicator for IDC. ..
  39. Clark C, Sage E. A prototypic matricellular protein in the tumor microenvironment--where there's SPARC, there's fire. J Cell Biochem. 2008;104:721-32 pubmed publisher
  40. Tripathi R, Mishra R. Interaction of Pax6 with SPARC and p53 in brain of mice indicates Smad3 dependent auto-regulation. J Mol Neurosci. 2010;41:397-403 pubmed publisher
    ..The Pax6 probably participates with p53 to regulate neuronal survival. It indicates that the interaction of Pax6, SPARC and p53 may influence Smad3-dependent auto-regulation of Pax6. ..
  41. Capper D, Mittelbronn M, Goeppert B, Meyermann R, Schittenhelm J. Secreted protein, acidic and rich in cysteine (SPARC) expression in astrocytic tumour cells negatively correlates with proliferation, while vascular SPARC expression is associated with patient survival. Neuropathol Appl Neurobiol. 2010;36:183-97 pubmed publisher
    ..While there is no association between the level of SPARC in the tumour cells and patient survival, increased tumour vascular SPARC expression is associated with decreased patient survival. ..
  42. Liddelow S, Dziegielewska K, M llg rd K, Phoenix T, Temple S, Vandeberg J, et al. SPARC/osteonectin, an endogenous mechanism for targeting albumin to the blood-cerebrospinal fluid interface during brain development. Eur J Neurosci. 2011;34:1062-73 pubmed publisher
    ..Using a marsupial, Monodelphis domestica, we demonstrate that the albumin-binding protein SPARC (osteonectin/BM-40/culture-shock protein) is present in a subset of choroid plexus epithelial cells from its first ..
  43. Seet L, Su R, Toh L, Wong T. In vitro analyses of the anti-fibrotic effect of SPARC silencing in human Tenon's fibroblasts: comparisons with mitomycin C. J Cell Mol Med. 2012;16:1245-59 pubmed publisher
    ..Together, these data demonstrate that SPARC knockdown in HTFs modulates fibroblast functions important for wound fibrosis and is therefore a promising strategy in the development of anti-scarring therapeutics. ..
  44. Haddadin R, Oh D, Kang M, Filippopoulos T, Gupta M, Hart L, et al. SPARC-null mice exhibit lower intraocular pressures. Invest Ophthalmol Vis Sci. 2009;50:3771-7 pubmed publisher
    ..SPARC-null mice have lower IOPs than do their WT counterparts with equal CCTs. The rate of aqueous turnover suggests that the mechanism is enhanced outflow resistance. ..
  45. Rainger J, van Beusekom E, Ramsay J, McKie L, Al Gazali L, Pallotta R, et al. Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-acromelic (Waardenburg Anophthalmia) syndrome in humans and mice. PLoS Genet. 2011;7:e1002114 pubmed publisher
    ..Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice. ..
  46. Okada I, Hamanoue H, Terada K, Tohma T, Megarbane A, Chouery E, et al. SMOC1 is essential for ocular and limb development in humans and mice. Am J Hum Genet. 2011;88:30-41 pubmed publisher
    ..Our findings indicate that SMOC1/Smoc1 is essential for ocular and limb development in both humans and mice...
  47. Thomas J, Canelos P, Luyten F, Moos M. Xenopus SMOC-1 Inhibits bone morphogenetic protein signaling downstream of receptor binding and is essential for postgastrulation development in Xenopus. J Biol Chem. 2009;284:18994-9005 pubmed publisher
    ..These findings provide a direct link between the extracellular matrix-associated protein SMOC and a signaling pathway of general importance in anatomic patterning and cell or tissue fate specification. ..
  48. Bhoopathi P, Chetty C, Dontula R, Gujrati M, Dinh D, Rao J, et al. SPARC stimulates neuronal differentiation of medulloblastoma cells via the Notch1/STAT3 pathway. Cancer Res. 2011;71:4908-19 pubmed publisher
    ..Findings show that SPARC-induced neuronal differentiation can sensitize medulloblastoma cells for therapy. ..
  49. McCurdy S, Baicu C, Heymans S, Bradshaw A. Cardiac extracellular matrix remodeling: fibrillar collagens and Secreted Protein Acidic and Rich in Cysteine (SPARC). J Mol Cell Cardiol. 2010;48:544-9 pubmed publisher
  50. Fuller H, Man N, Lam L, Shamanin V, Androphy E, Morris G. Valproate and bone loss: iTRAQ proteomics show that valproate reduces collagens and osteonectin in SMA cells. J Proteome Res. 2010;9:4228-33 pubmed publisher
    ..The collagen-binding glycoprotein, osteonectin (SPARC, BM-40) was one of the few other proteins that were significantly reduced by valproate treatment...
  51. Podgorski I, Linebaugh B, Koblinski J, Rudy D, Herroon M, Olive M, et al. Bone marrow-derived cathepsin K cleaves SPARC in bone metastasis. Am J Pathol. 2009;175:1255-69 pubmed publisher
    ..This is the first study implicating bone marrow cathepsin K in regulation of biological activity of SPARC in bone metastasis. ..
  52. Arnold S, Mira E, Muneer S, Korpanty G, Beck A, Holloway S, et al. Forced expression of MMP9 rescues the loss of angiogenesis and abrogates metastasis of pancreatic tumors triggered by the absence of host SPARC. Exp Biol Med (Maywood). 2008;233:860-73 pubmed publisher
    ..These results suggest that SPARC and MMP9 interact to regulate many stages of tumor progression including ECM deposition, angiogenesis and metastasis. ..
  53. Delany A, McMahon D, Powell J, Greenberg D, Kurland E. Osteonectin/SPARC polymorphisms in Caucasian men with idiopathic osteoporosis. Osteoporos Int. 2008;19:969-78 pubmed
    Animal models suggest a role for osteonectin/SPARC in determination of bone mass...