Osteopontin: a multifunctional molecule regulating chronic inflammation and vascular disease.

نویسندگان

  • Marta Scatena
  • Lucy Liaw
  • Cecilia M Giachelli
چکیده

Osteopontin (OPN) is a multifunctional molecule highly expressed in chronic inflammatory and autoimmune diseases, and it is specifically localized in and around inflammatory cells. OPN is a secreted adhesive molecule, and it is thought to aid in the recruitment of monocytes-macrophages and to regulate cytokine production in macrophages, dendritic cells, and T-cells. OPN has been classified as T-helper 1 cytokine and thus believed to exacerbate inflammation in several chronic inflammatory diseases, including atherosclerosis. Besides proinflammatory functions, physiologically OPN is a potent inhibitor of mineralization, it prevents ectopic calcium deposits and is a potent inducible inhibitor of vascular calcification. Clinically, OPN plasma levels have been found associated with various inflammatory diseases, including cardiovascular burden. It is thus imperative to dissect the OPN proinflammatory and anticalcific functions. OPN recruitment functions of inflammatory cells are thought to be mediated through its adhesive domains, especially the arginine-glycine-aspartate (RGD) sequence that interacts with several integrin heterodimers. However, the integrin receptors and intracellular pathways mediating OPN effects on immune cells are not well established. Furthermore, several studies show that OPN is cleaved by at least 2 classes of proteases: thrombin and matrix-metalloproteases (MMPs). Most importantly, at least in vitro, fragments generated by cleavage not only maintain OPN adhesive functions but also expose new active domains that may impart new activities. The role for OPN proteolytic fragments in vivo is almost completely unexplored. We believe that further knowledge of the effects of OPN fragments on cell responses might help in designing therapeutics targeting inflammatory and cardiovascular diseases.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

A Multifunctional Molecule Regulating Chronic Inflammation and Vascular Disease

Osteopontin (OPN) is a multifunctional molecule highly expressed in chronic inflammatory and autoimmune diseases, and it is specifically localized in and around inflammatory cells. OPN is a secreted adhesive molecule, and it is thought to aid in the recruitment of monocytes-macrophages and to regulate cytokine production in macrophages, dendritic cells, and T-cells. OPN has been classified as T...

متن کامل

Molecular mechanisms regulating immune responses in thromboangiitis obliterans: a comprehensive review

Thromboangiitis obliterans (TAO) is a thrombotic-occlusive as well as an inflammatory peripheral vascular disease with unknown etiology. Recent evidence has supported the immunopathogenesis of the disease, however, the factors contributing to the altered immune function and vascular tissue inflammation are still unclear. This review was intended to collate the more current knowledge on the regu...

متن کامل

Vitamin D receptor agonists increase klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet

Vascular calcification is common in chronic kidney disease, where cardiovascular mortality remains the leading cause of death. Patients with kidney disease are often prescribed vitamin D receptor agonists (VDRAs) that confer a survival benefit, but the underlying mechanisms remain unclear. Here we tested two VDRAs in a mouse chronic kidney disease model where dietary phosphate loading induced a...

متن کامل

Inflammation and Vascular Calcification Causing Effects of Oxidized HDL are Attenuated by Adiponectin in Human Vascular Smooth Muscle Cells

The role of oxidized high-density lipoprotein (oxHDL) and the protective effects of adiponectin in terms of vascular calcification is not well established. This study was conducted to investigate the effects of oxHDL with regards to inflammation and vascular calcification and to determine the protective role of adiponectin in attenuating the detrimental effects of oxHDL. Cell viability, mineral...

متن کامل

Synthesis and Anti-inflammatory Performance of Newly Cyclizine Derivatives on Adult Male Wistar Rats

Cyclizine (1-benzhydryl-4-methyl-piperazine, CAS 82-92-8, CYC, I), a piperazine derivative, belongs to H1 antihistamine group of drugs that shows such pharmacological properties as anti-inflammatory, anti-allergic and anti-platelet effects, similar to other H1-receptor antagonists. In this study, two new tolyl and cumene derivatives of I (1-ethyl-4-[(p-isopropylphenyl) (p-tolyl) methyl]-piperaz...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Arteriosclerosis, thrombosis, and vascular biology

دوره 27 11  شماره 

صفحات  -

تاریخ انتشار 2007