Osteopontin Overview

Osteopontin is a protein, widely distributed in a variety of tissues and cells, to participate in tissue repair, metabolism and other functions.

In 1979, Senger et al. First reported a phosphorylated glycoprotein associated with malignant transformation, which contains the RGD (sperm-gly-aspartate) integrin binding domain, which is known as a transforming-associated phosphoprotein. Later Franzen et al. Isolated a phosphate protein from bone, which is similar to the phosphoprotein found by Senger et al., Because it is a product of the cell in the bone matrix and can bridge the mineral in the cell with the matrix , It will be named OPN. OPN was first found in the bone matrix and teeth, and later some scholars in the kidney, inner ear, decidua, placenta, smooth muscle, activated T cells, macrophages and other different tissues and cells also found OPN, OPN has also been (BSP-1), BSP-1, BSP-1), which are known as 44kD osteoprotegerin, PP69, osteocalcin 1, urinary protein, early T lymphocyte activity 1 (Eta-1) and secretory phosphoprotein 1SPP- KD bone phosphoprotein and 2alphaR. OPN, OPN, OPN, bovine OPN, chicken OPN and rabbit OPN cDNA have been cloned since 1986. In recent years, OPN as a new type of cytokines, in the early cellular immune response, granulomatous inflammation, tumorigenesis and metastasis in the role of much attention.

Osteopontin distribution

OPN can be expressed in various tissues of different animals, such as bone, kidney (fetal kidney and adult kidney), lung, liver, bladder, pancreas, breast, testis, brain, bone marrow and decidua. Osteoblasts, osteoclasts, chondrocytes, neurons, epithelial cells, endothelial cells, vascular smooth muscle cells (SMC), activated T cells, MФ and natural killer cells (SMCs) can also be expressed in different cell types ( NK) cell subsets; OPN also exists in normal body fluids, such as serum, milk, urine, bile. OPN expression was increased in lung cancer, breast cancer, gastric cancer, ovarian cancer, prostate cancer, thyroid cancer, skin cancer and various transformed cell lines. OPN expression was also elevated in the pathological state (immunological disease, inflammation and tumor) OPN is also present.

OPN expression in normal arterial walls was minimal or almost absent, but OPN expression was significantly increased in foam cells or at calcified sites in macrophages and smooth muscle cells of atherosclerotic plaques in atherosclerotic plaques , Endothelial cells can express OPN mRNA and synthetic OPN. The role of endothelial cells, smooth muscle cells, fibroblasts and OPN dependent on RGD and Ca2 +, anti-avβ3 antibody can partially block the migration of these cells to OPN.

The biological effects of osteopontin

1. Cell adhesion OPN binds to various integrin receptors on the cell surface, depending on the RGD sequences (αvβ1, αvβ3, αvβ5, αvβ1, α8β1) and the independent RGD sequences (α4β1, α9β1) . OPN binds to transformed JB6 cells and HL60 cells (αvβ5 and α4β1 receptors), and OPN binds to transformed fibroblasts in a non-RGD form. OPN, which is broken by thrombin, enhances OPN and APP activation and phorbol ester-activated platelets And B lymphocyte adhesion and T cell adhesion.

2. Cell recruitment In vitro: OPN is a chemotactic agent that directs the migration of fibroblasts in a dose-dependent manner (5.0-40 mg / L); it stimulates the migration of rat and bovine smooth muscle cells , Can support adhesion to human and mouse T cells, in vivo subcutaneous injection of OPN, in the vicinity of the injection site, OPN can directly induce chemotaxis and indirectly help M to other chemotactic agent movement. In addition OPN can promote osteoclast and B cell chemotaxis.

3. Cytokine expression: OPN enhanced Th1 and inhibited the expression of Th2 cytokines, it is directly induced by LPS stimulation to produce IL-12, inhibition of IL-10 expression. The effect on IL-12 is dependent on OPN phosphorylation. OPN can polarize the early Th1 cytokine response. OPN also synergistically stimulates human T cell proliferation and promotes the expression of Th1 cytokines by human mononuclear cells. Intra-articular OPNs are an inherent inhibitor of IL-1, NO and PGE2 production.

4. Signal transduction: osteopontin as a matrix of functional non-collagen protein, mainly through two mechanisms to play the role of cell signaling molecules. One is to intramolecular RGD motifs and integrins (integrin) family of molecules; the second is with the cell surface adhesion glycoprotein CD44 to non-RGD dependent manner. Both modes of action mediate cell adhesion, migration and proliferation by activating intracellular signaling pathways. OPN binds to the integrin receptor and activates the signal transduction cascade to promote the expression of NF-кB. OPN can induce the phosphorylation of FAK and Paxillin in skeletal proteins. Change, but also affect the intracellular Ca2 + concentration.

5. Tumorigenesis and metastasis: Matrix-derived tumors are usually associated with increased expression of OPN, overexpression of OPN is associated with the progression of human gastric cancer. OPN stimulates cell signal transduction to promote the malignant development of tumors and can enhance the survival of metastatic cells. OPN is a paracrine and autocrine modulator of prostate cancer growth and development, and recombinant OPNs can survive by binding to H-factor.

6. Mineralization: OPN contains an acidic domain that interacts with the mineral surface of the extracellular matrix. OPN can inhibit the calcification of cultured vascular smooth muscle cells.

7. Cellular immunity: Th1-mediated immune deficiency in OPN knockout mice and delayed-onset hypersensitivity to HSV after HSV-1 infection in the cornea, but no HSV-associated keratitis , Which encodes the OPN gene and the mouse anti-rickettsial gene (RicR). The RicR allele responsible for the early defect of OPN is associated with rickettsial infection, whereas high-level OPN mice express Rickettsia OPN plays an important role in Th1 cell-mediated granuloma formation.

8. Other: it can cause monocyte differentiation; accelerate angiogenesis; involved in tissue remodeling, such as bone resorption, angiogenesis and wound healing; induced urokinase-type plasminogen activator (UPA) expression; inhibition of endothelial cells (INOS) activity in renal tubular epithelial cells via LPS and IFN-γ; OPN is a negative feedback regulator of INOS in murine M cells. It is also associated with atherosclerosis, autoimmune diseases and other inflammatory diseases (pulmonary fibrosis).

Summary of osteopontin

In short, osteopontin as a new cytokine, plays an important role in the human body. More and more research, confirmed the importance of osteopontin, I believe that the future will find more of its magical effect, for human disease research and treatment to contribute.