Osteopontin – a multifunctional protein and its impact on an insulin resistance development


  • Katarzyna Musialik Department of Internal Diseases, Metabolic Disorders, and Hypertension, Poznan University of Medical Sciences, Poland
  • Damian Skrypnik Department of Internal Diseases, Metabolic Disorders, and Hypertension, Poznan University of Medical Sciences, Poland
  • Paweł Bogdański Department of Internal Diseases, Metabolic Disorders, and Hypertension, Poznan University of Medical Sciences, Poland
  • Monika Szulińska Department of Internal Diseases, Metabolic Disorders, and Hypertension, Poznan University of Medical Sciences, Poland




osteopontin, coronary artery disease, insulin resistance


Osteopontin (OPN) is one of the many physiological elements creating human musculoskeletal system. It is suspected that this protein is one of the most important mediators responsible for osseous tissue mass resorption, regulated by parthormon. The origin of its name comes from one of its physiological action – rebuilding of the bone mass structure (osteo – bone, pontin – bridge). Osteopontin fulfils many different actions being secreted by many different types of cells, including macrophages, lymphocytes, epithelial cells, vascular smooth muscle cells, and osteoblasts. OPN plays an important part in inflammatory process. It provokes macrophages and dendritic cells to movement into the destination where inflammatory process takes place. It also stimulates macrophages to interleukin 12 (IL12) and interferon ? (IFN ?) secretion. Increased OPN concentration in blood stream might be regarded as a novel, independent indicator of coronary artery disease. Osteopontin plays an important role in macrophage infiltration of the adipose tissue and at the same time contributes to insulin resistance. Obesity induces chronic, low-grade tissue inflammation. Positive correlation was observed between body mass index (BMI) and number of macrophages accumulated in the fat tissue. Once aroused monocytes infiltrate the adipose tissue, which leads to persisting chronic inflammation. At the same time the excreted by them cytokines may be connected with the mechanisms of obesity-induced insulin resistance.


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Senger DR, Wirth DF, Haynes RO. Transformed mammalian cells secrete specific proteins and phosphoproteins. Cell. 1979;16:885–93.

Ishii T, Ohshima S, Ishida T, Kawase I, Mima T, Tabunoki Y, et al. Mice with osteopontin deletion remain predisponed to collagen-inducedarthritris. Arthritis Rheum. 2004; 50:669–71.

Wrana JL, Zang Q, Sodek J. Full lengh cDNA sequence of porcine secreted phosphoprotein-I (Spp-I, osteopontin). Nucleic Acid Res. 1989;17:10119–23.

Craig AM, Nemir M, Mukherjee BB, Chambers AF, Denhardt DT. Identification of the major phosphoprotein secreted by many rodent cell lines as 2ar/osteopontin: enhanced expression in H-ras-transformed 3T3 cells. Biochem Biophys Res Comm. 1988;157:166–73.

Shiraga H, Min W, VanDusen WJ, Clayman MD, Miner D, Terrell CH, et al. Inhibition of calcium oxalate crystal growth in vitro by uropontin: another member of the aspartic acid-rich protein superfamily. Proc Natl Acad Sci. 1992;89:426–30.

Oldberg A, Franzen A, Heinega D. Cloning and sequence analysisof rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. Proc Natl Acad Sci. 1986;83:8819–23.

Reinholt FP, Hultenby K, Oldberg A, Heinegard D. Osteopontin – a possible anchor of osteoclasts to bone. Proc Natl Acad Sci. 1990;87:4473–5.

Ihara H, Denhardt DT, Furuya K, Yamashita T, Muguruma Y, Tsuji K, et al. Parathyroid hormone – induced bone resorption does not occur in the absence of osteopontin. J Biol Chem. 2001;276:13065–71.

Mazzali M, Kipari T, Ophascharoensuk V, Wesson J, Johnson R, Hughes J. Osteopontin – a molecule for all seasons. Q J Med. 2002;95:3–13.

Różański W, Klimek L, Jakubowski K, Miękoś E, Górkiewicz Z. Niekrystaliczne składniki kamieni moczowych. Urol Pol. 2003;56:7–10.

Gravallese EM. Osteopontin a bridge between bone and the immune system. J Clin Invest. 2003;112:147–9.

El-Tanani MK, Campbell FC, Kurisetty V, Jin D, McCann M, Rudland PS. The regulation and role of osteopontin in malignant transformation and cancer. Cytokine Growth Factor Rev. 2006;17:463–674.

Hullinger TG, Pan Q, Viswanathan HL, Somerman MJ. TGF beta and BMP-2 activation of the OPN promoter: roles of smad- and hox-binding elements. Exp Cell Res. 2001;262:69–74.

Ashkar S, Weber GF, Panoutsakopoulou V, Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science. 2000;287:860–4.

Gomez-Ambrosi J, Catalan V, Ramirez B, Rodriguez A, Colina I, Silva C, et al. Plasma osteopontin levels and expression in adipose tissue are increased in obesity. J Clin Endocrinol Metab. 2007;92:3719–27.

Guo H, Cai CQ, Schroeder RA, Kuo PC. Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages. J Immunol. 2001;166:1079–86.

Kiefer FW, Zeyda M, Todoric J, Huber J, Geyeregger R, Weichhart T, Aszmann O, Ludvik B, Silberhumer GR, Prager G, Stulnig TM. Osteopontin expression in human and murine obesity: extensive local up-regulation in adipose tissue but minimal systemic alterations. Endocrinology. 2008;149:1350–7.

Mason CK, McFarlane S, Johnston PG. Agelastatin A: a novel inhibitor of osteopontin-mediated adhesion, invasion, and colony formation. Mol Cancer Ther. 2008;7: 548–58.

Ohmori R, Momiyama Y, Taniguchi H, Takahashi R, Kusuhara M, Nakamura H, et al. Plasma osteopontin levels are associated with the presence and extent of coronary artery disease. Atherosclerosis. 2003;170:333–7.

Fitzpatrick LA, Severson A, Edwards WD, Ingram RT. Diffuse calcification in human coronary arteries. Association of osteopontin with atherosclerosis. J Clin Invest. 1994; 94:1597–604.

Bjerre M, Pedersen SH, Mogelvang R, Lindberg S, Jensen JS, Galatius S, et al. A.High osteopontin levels predict long-term outcome after STEMI and primary percutaneous coronary intervention. Eur J Prev Cardiol. 2013; 20:922–9.

Takemoto M, Yokote K, Nishimura M, Shigematsu T, Hasegawa T, Kon S, et al. Enhanced expression of osteopontin in human diabetic artery and analysis of its functional role in accelerated atherogenesis. Arterioscler Thromb Vasc Biol. 2000;20:624–8.

Nomiyama T, Perez-Tilve D, Ogawa D, Gizard F, Zhao Y, Heywood EB, et al. Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. J Clin Invest. 2007;117:2877–88.

Kiefer F, Zeyda M, Gollinger K, Pfau B, Neuhofer A, Weichhart, et al. Neutralization of Osteopontin Inhibits Obesity-Induced Inflammation and Insulin Resistance. Diabetes. 2010;59:935–46.

Samuvel DJ, Sundararaj KP, Li Y, Lopes-Virella MF, Huang Y. Interaction, Toll-like Receptor 4 Activation, and High Glucose Synergistically Up-regulate Osteopontin Expression via an Interleukin 6-mediated Mechanism J Biol Chem. 2010;285:3916–27.

Bogdański P, Musialik K. Metabolic syndrome – diagnosis and therapy. Lekarz. 2010;14:40–4.

Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003; 112:1796–08.

Ahmad R, Al-Mass A, Al-Ghawas D, Shareif N, Zghoul N, Melhem M, et al. Interaction of Osteopontin with IL-18 in Obese Individuals: Implications for Insulin Resistance. PLOS ONE 20.




How to Cite

Musialik K, Skrypnik D, Bogdański P, Szulińska M. Osteopontin – a multifunctional protein and its impact on an insulin resistance development. JMS [Internet]. 2014 Jun. 30 [cited 2024 Jun. 16];83(2):173-6. Available from: https://jms.ump.edu.pl/index.php/JMS/article/view/64



Review Papers
Received 2016-02-17
Published 2014-06-30