Involvement Of Osteopontin Research Articles

Serum Osteopontin as a Potential Marker for Metastasis and Prognosis in Primary Osteogenic Sarcoma: A Systematic Review.

Osteosarcoma (OS), a primary malignant bone tumor, poses significant challenges in diagnosis and prognosis. It is a painful medical burden, and treating it is still a difficult issue. Osteopontin (OPN), a multifunctional extracellular matrix protein, has emerged as a promising biomarker in this context. This systematic review explores the role of OPN as a diagnostic and prognostic marker in OS, highlighting its potential in enhancing early detection, monitoring disease progression, and predicting patient outcomes. Various studies have demonstrated elevated levels of OPN in OS patients, correlating with tumor aggressiveness, metastatic potential, and poor prognosis. In addition, OPN's involvement in tumor microenvironment regulation and metastatic processes underscores its clinical relevance as a biomarker. For this systematic review, comprehensive literature searches were conducted in the PubMed databases for researchpublished between the database's establishment and November 11, 2022. Out of the nine studies that were available for analysis, a higher level of OPN in primary osteogenic sarcoma patients indicates a poorer prognosis and higher incidence of metastasis. OS has not shown commensurable progress with concerns to treatment approches and survical outcomes. However, the discovery of a biological marker that can predict metastasis and severity will be a groundbreaking development for advancements in OS diagnosis and treatment. Therefore, understanding the intricate interplay between OPN and OS pathogenesis holds promise for improving patient management and developing targeted therapeutic strategies.

Involvement of osteopontin, EpCAM, estrogen receptor-alpha, and carbonic anhydrase IX protein in managing lung cancer via Berberine-loaded liquid crystalline nanoparticles

Involvement of osteopontin, EpCAM, estrogen receptor-alpha, and carbonic anhydrase IX protein in managing lung cancer via Berberine-loaded liquid crystalline nanoparticles

Diacerein protects against renal ischemia/reperfusion-induced kidney and lung injuries: involvement of osteopontin and Nrf-2/HO-1 pathway.

Diacerein protects against renal ischemia/reperfusion-induced kidney and lung injuries: involvement of osteopontin and Nrf-2/HO-1 pathway.

Pathophysiology-based treatment of urolithiasis.

Urolithiasis, a complex multifactorial disease, results from interactions between environmental and genetic factors. Epidemiological studies have shown the association of urolithiasis with a number of lifestyle-related diseases, including cardiovascular diseases, hypertension, chronic kidney disease, diabetes and metabolic syndrome. Elucidation of the mechanisms underlying urinary stone formation will enable development of new preventive treatments. The present article reviews the epidemiology, pathophysiology and potential treatment of urolithiasis. Recent literature has shown that oxidative stress and reactive oxygen species could be one such mechanistic pathway. Calcium oxalate crystals adhering to renal tubular cells are incorporated into the cells through the involvement of osteopontin. Stimulation of crystal-cell adhesion impairs acceleration of the mitochondrial permeability transition pore in tubular cells, resulting in mitochondrial collapse, oxidative stress and activation of the apoptotic pathway in the initial steps of renal calcium crystallization. With regard to genetic factors, studies show that single nucleotide polymorphisms in genes encoding calcium-sensing receptor, vitamin D receptor and osteopontin are correlated with urolithiasis. Genome-wide association studies have shown that CLDN14 and NPT2 are associated with urolithiasis in Caucasian and Japanese populations, respectively. Thus, single nucleotide polymorphism analysis would aid in the prediction of urolithiasis risk and recurrence. New diagnostic methods and preventive approaches, along with complete removal of stones, will improve the management of urolithiasis.

The involvement of osteopontin and matrix metalloproteinase- 9 in the migration of endometrial epithelial cells in patients with endometriosis.

BackgroundEndometriosis, which shares certain characteristics with cancers, may cause abnormal expression of proteins involved in cell migration. Endometrial epithelial cells (EECs) are believed to play an important role in endometriotic migration. The aim of this study was to investigate the relationship between the expression of osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) in endometriotic migration.MethodsWe performed primary culture of EECs and investigated the expression of OPN and MMP-9 in EECs regulated by 17beta-estradiol (E2). OPN-specific siRNA interference was used to down-regulate OPN and to explore the corresponding change in MMP-9 expression. Real-time RT-PCR, western blot analysis and flow cytometry were used to determine the expression levels of OPN and MMP-9. Gelatin zymography was performed to observe the enzymatic activity of MMP-9 in conditioned media. Transwell and wound scratch assays were performed to investigate the migration ability of EECs.ResultsThe expression levels of OPN and MMP-9 in normal EECs (NEECs) were inferior to those in EECs from patients with endometriosis (EEECs). The expression levels of OPN and MMP-9 from stage III/IV EEECs and secretory-phase EECs were higher than those of stage I/II EEECs or proliferative-phase EECs. The expression levels of OPN and MMP-9 in EEECs were increased by E2 treatment and remarkably decreased by siRNA interference. Active MMP-9 expression increased with E2 treatment and decreased with siRNA treatment in EEECs compared with the same treatments in NEECs. The migratory abilities of EEECs were enhanced after cells were treated with E2; in contrast, these abilities were reduced by siRNA interference. In NEECs, active MMP-9 and cellular migration abilities were only minimally influenced by E2 and siRNA treatment.ConclusionsThe present study suggests that the up-regulation of MMP-9 via activation of OPN induced by estrogen may correlate with the migration of endometrial epithelial cells in patients with endometriosis.

The involvement of osteopontin and β3 integrin in implantation and endometrial receptivity in an early mouse pregnancy model

ObjectiveTo explore the roles of osteopontin and β3 integrin in successful implantation. Study designIn this study, an early pregnant mouse model was established by peritoneal injection of pregnant mare serum gonadotropin and human chorionic gonadotropin (PMSG+hCG). The expression of osteopontin (OPN) and β3 integrin on the endometrium was measured by immunohistochemistry, RT-PCR, and western blot. The function of OPN and β3 integrin in implantation was investigated by intrauterine injection of OPN and β3 integrin antibody. ResultsWe found that PMSG+hCG injection significantly increased the number of blastocysts during implantation as well as the concentration of estradiol and progesterone in serum and endometrium tissues. OPN and β3 integrin were co-expressed in luminal epithelium and their levels dynamically changed from day 4 to day 8 of pregnancy with peak expression on day 5. The percentages of OPN and β3 integrin positive cells in the luminal epithelium were significantly higher in PMSG+hCG-stimulated mice on day 5 than in control mice. Functional blockade of OPN and β3 integrin significantly inhibited implantation. ConclusionsThis study suggests that co-expression of OPN and β3 integrin is a biological marker for good endometrial receptivity and that both proteins play a crucial role in blastocyst implantation.

Biomolecular mechanism of urinary stone formation involving osteopontin

Urinary stones consist of two phases-an inorganic (mineral) phase and an organic (matrix) phase. Studies on the organic components of kidney stones have been undertaken later than those on the inorganic components. After osteopontin was identified as one of the matrix components, the biomolecular mechanism of urinary stone formation became clearer. It also triggered the development of new preventive treatments. Osteopontin expression is sporadically observed in normal distal tubular cells and is markedly increased in stone-forming kidneys. Calcium oxalate crystals adhering to renal tubular cells are incorporated into cells by the involvement of osteopontin. Stimulation of crystal-cell adhesion impairs the opening of mitochondrial permeability transition pores (mPTP) in tubular cells and produces oxidative stress, apoptosis, and osteopontin expression. Macrophages phagocytose and digest a small amount of crystals, but many crystals aggregate into a mass containing osteopontin and epithelial cell debris and are excreted into the renal tubular lumen, becoming nuclei of urinary stones. This biomolecular mechanism is similar to atherosclerotic calcification. Based on these findings, new preventive treatments have been developed. Dietary control such as low-cholesterol intake and the ingestion of antioxidative foods and vegetables have successfully reduced the 5-year recurrence rate. Osteopontin antibodies and cyclosporine A, which blocks the opening of mPTP, have markedly inhibited the expression of osteopontin and urinary stone formation in animal models.

Osteopontin, a protein with cytokine-like properties: a possible involvement in pemphigus vulgaris

Pemphigus is an autoimmune blistering disease characterized by severe and chronic course, histopathologically characterized by infiltration of a large quantity of eosinophils, neutrophils, and activated Th1 and Th2 cells around the blister. Polarization of Th cells to Th1 or Th2 phenotypes, a critical aspect of cell-mediated immunity, is influenced by production of early cytokines, including osteopontin. To determine the involvement of osteopontin in pemphigus vulgaris patients in active stage of the disease, auto-antibodies to desmoglein-1 and desmoglein-3 and plasmatic osteopontin levels were examined by ELISA tests. In this work, significant plasmatic level of osteopontin in PV patients with active stage of disease were found particularly in those patients with both skin and oral pemphigus. OPN might drive the immune responses playing an important role in pemphigus onset.

Involvement of osteopontin and its signaling molecule CD44 in clinicopathological features of adult T cell leukemia

We previously reported that the osteopontin (OPN) gene as well as CD44 is trans-activated by the Tax protein of HTLV-1, however the synthesis of both in adult T cell leukemia (ATL) has not been described yet. Here we showed the expression of these molecules in plasma and tissue of ATL. Significant differences were found among the normal and four subtypes of 27 ATL patients in plasma levels of OPN (p=3.6×10−6) and soluble CD44 (p<0.001) and they were significantly related to each other (p<0.002). Also they were significantly associated with the performance status, total number of involved lesions, and lactic dehydrogenase, and inversely with lymphocyte count (p<0.01). Immunohistochemical staining of lymph-nodes and skin from 7 ATL patients using anti-OPN and anti-CD44 antibodies demonstrated that both expressions were weak/moderate in ATL cells but moderate/strong in infiltrated macrophages in 6 patients. These results demonstrate that OPN and CD44 play important roles in tumor formations and their products in plasma could be markers of the severity in ATL.

Malignant Pleural Mesothelioma Prognostic Marker: A Review of Osteopontin and Soluble Mesothelin Peptides

This article is a review of a series of three studies that proved the involvement of osteopontin as a prognostic marker in malignant pleural mesothelioma (MPM) cancers. The approach used involved synthesizing and analysing the three articles. The first proves the utilization of osteopontin and mesothelin for diagnostic and prognostic assessment of MPM in patients previously exposed to asbestos and those with pleural metastasis. The second proves that immunohistochemical analysis identified osteopontin to have a prognostic role from its expression in MPM. The third uses the specificity and sensitivity of serum osteopontin to distinguish patients with plueral mesothelioma from subjects with asbestos-related non-malignant diseases. Overall, these remarkable findings are important for understanding of expression of osteopontin in malignant mesothelial cells and in patients with MPM. The use of osteopontin as a prognostic marker in MPM is promising and such fine molecular studies certainly help in bringing osteopontin closer to clinical practice. Keywords : Osteopontin, Mesothelioma, Prognostic marker Tropical Journal of Pharmaceutical Research December 2010; 9 (6): 605-613

Involvement of Osteopontin in the Matrix-Degrading and Proangiogenic Changes Mediated by Nicotine in Pancreatic Cancer Cells

BackgroundSubstantial evidence indicates that exposure to cigarette smoke is associated with an elevated risk of pancreatic ductal adenocarcinoma (PDA). However, the mechanisms underlying the effects of nicotine on the development or progression of PDA remain to be investigated. Previously, we showed that nicotine promotes the expression of osteopontin c (OPNc), an isoform of OPN protein that confers on cancer cells a migratory phenotype. In this study, we explored the potential prometastatic role of nicotine in PDA through studying its effect on the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) and evaluated the role of OPN in mediating these effects. Materials and MethodsMMP-9 and VEGF mRNA and protein were analyzed in PDA cells treated with or without nicotine (3–300 nM). Transient transfection and luciferase-labeled promoter studies evaluated the effects of OPNc and OPN protein on the transcription and translation of MMP-9 and VEGF. Real-time PCR and immunohistochemistry were used to analyze the mRNA expression levels and localization of OPN, MMP-9, and VEGF proteins in matched invasive human PDA and surrounding nonmalignant tissues. Results and DiscussionNicotine significantly enhanced the expression of MMP-9 and VEGF mRNA and protein in PDA cells. Blocking OPN with siRNA or OPN antibody prevented the nicotine-mediated increase of both MMP-9 and VEGF. Transient transfection of OPNc gene in PDA cells or their treatment with recombinant OPN protein significantly (p < 0.05) increased MMP-9 and VEGF mRNA expression levels and induced their promoter activities. In invasive PDA lesions, MMP-9 mRNA levels were significantly (p < 0.005) higher in smokers vs. nonsmokers. VEGF protein co-localized with MMP-9 and OPN in the malignant ducts and correlated well with their higher levels in invasive PDA lesions. ConclusionsOur data show for the first time that cigarette smoking and nicotine may contribute to PDA metastasis through inducing MMP-9 and VEGF and suggest that OPN plays a central role in mediating these effects. The presence of OPN as a downstream effector of nicotine that is capable of mediating its prometastatic effects in PDA cells is novel and could provide a unique therapeutic target to control pancreatic cancer aggressiveness, especially in the cigarette-smoking population.

589 Involvement of Osteopontin in the Matrix Degrading and Proangiogenic Changes Mediated by Nicotine in Pancreatic Cancer Cells

Background Substantial evidence indicates that exposure to cigarette smoke is associated with an elevated risk of pancreatic ductal adenocarcinoma (PDA). However, the mechanisms underlying the effects of nicotine on the development or progression of PDA remain to be investigated. Previously, we showed that nicotine promotes the expression of osteopontin c (OPNc), an isoform of OPN protein that confers on cancer cells a migratory phenotype. In this study, we explored the potential prometastatic role of nicotine in PDA through studying its effect on the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) and evaluated the role of OPN in mediating these effects.

Involvement of osteopontin as a core protein in craniopharyngioma calcification formation

Matrix proteins are considered to be essential for biomineralization and to be important factors in cranioharyngioma calcification. Osteopontin (OPN) is a noncollagenous, acidic bone-matrix glycoprotein, which binds tightly to hydroxyapatite and appears to form an integral part of the mineralized matrix, probably important to the integrity of cell-matrix interactions. OPN is also a ligand for a cell membrane receptor, CD44v6, which is required for efficient OPN binding. To investigate the role of OPN in craniopharyngioma calcification formation, we studied the involvement of OPN and CD44v6 in craniopharyngiomas. Immunohistochemical staining was used in human craniopharyngiomas to detect the relationship of OPN and degree of calcification, and immunogold localization of OPN was done to identify cell secretory granules. OPN expression was elevated in calcification craniopharyngioma samples. Immunohistochemical staining demonstrated that the OPN expression level was significantly correlated with the degree of calcification (chi(2) = 29.987, P < 0.001); meanwhile, immunoelectron microscopy revealed subcellular sites of OPN presenting in epithelial cells, suggesting that the OPN protein is probably synthesized and secreted by stellate reticulum-like cells and ameloblast-like cells. At the same time, OPN expression was paralleled by cell surface reactivity for CD44v6, an OPN functional receptor. These results suggest that OPN is possibly involved as a core protein in the formation of craniopharyngioma calcification.

Involvement of osteopontin as a core protein in cholesterol gallstone formation

Matrix proteins are considered to be essential for biomineralization and to be important factors in the formation and growth of gallstones. Osteopontin (Opn) is a noncollagenous, acidic bone-matrix glycoprotein, which is sialated and phosphorylated and which has a cell-binding peptide sequence of glycine-arginine-glycine-aspartate-serine (GRGDS). To investigate the role of Opn in cholesterol gallstone formation, we have studied the involvement of Opn in cholesterol gallstone formation in the human gallbladder wall, in the stones, and in the mouse gallbladder using a gallstone experimental model. Immunohistochemical staining was used in the human gallbladder wall and human gallstones and the determination of mRNA expression by reverse transcriptase-PCR was used in the mouse gallbladder of a gallstone experimental model. The epithelium of stone-laden gallbladders demonstrated high Opn reactivity, as did the core of the stones. Microscopically detected early stones without macroscopic evidence of lithiasis showed the same immunoreactivity as larger stones. Stone-laden gallbladders were infiltrated by macrophages showing intense Opn expression. In gallstone-forming mice, the expression of Opn mRNA and its protein were significantly increased in the gallbladder wall in the early phase of a lithogenic diet intake, before the initiation of inflammation. These results suggest that Opn is possibly involved as a core protein in the formation of cholesterol gallstones.

Preventive Effects of Nutritional Doses of Polyphenolic Molecules on Cardiac Fibrosis Associated with Metabolic Syndrome: Involvement of Osteopontin and Oxidative Stress

We previously showed that grape extracts enriched in different polyphenolic families were similarly able to prevent reactive oxygen species (ROS) production, although having differential effects on various features of metabolic syndrome when administered at a dose of 21 mg/kg to the fructose (60%)-fed rat (a model of metabolic syndrome). In the present work, we analyzed on the same model the effect of pure polyphenolic molecules (catechin, resveratrol, delphinidin, and gallic acid) administered at a dose of 2.1 mg/kg. Delphinidin and gallic acid prevented insulin resistance, while gallic acid prevented the elevation of blood pressure. All molecules prevented cardiac ROS overproduction and NADPH overexpression. We also showed that fructose feeding was associated with cardiac fibrosis (accumulation of collagen I) and expression of osteopontin, a factor induced by ROS and a collagen I expression inducer. Collagen I and osteopontin expressions were prevented by the administration of all polyphenolic molecules. The potential use of polyphenols in the prevention of cardiac fibrosis should be further explored.

The involvement of osteopontin and its receptors in multiple myeloma cell survival, migration and invasion in the murine 5T33MM model

Multiple myeloma (MM) is a malignancy characterised by the accumulation of monoclonal plasma cells in the bone marrow. Different reports indicate the expression of CD44 variant isoforms (CD44v) by MM cells. Osteopontin (OPN), which is expressed by MM cells, is known to be a ligand for CD44v6. In this study, we investigated the role of OPN with emphasis on a functional correlation between OPN and CD44v in the 5T33MM model. Our group reported the expression of CD44v by 5T33MM cells. Using this model, we have demonstrated the secretion of OPN by 5T33MM cells. OPN affected 5T33MM cell survival by increasing proliferation and inhibiting apoptosis. OPN also stimulated 5T33MM cell migration, transendothelial migration and matrix metalloproteinase-9 activity. We confirmed the proliferative and migratory effects of OPN on human MM cells. By applying inhibiting anti-CD44v6 antibodies, we found that OPN stimulated cell proliferation by engaging this isoform. Anti-CD44v antibodies and RGD peptides both inhibited cell migration, suggesting an involvement of both, CD44v isoforms and integrins. In conclusion, OPN may act as a mediator of MM cell survival by engaging CD44v. The protein is further involved in migration and invasion of MM cells through the activation of either alphavbeta3 integrin or CD44v isoforms.

Osteopontin Expression Correlates with Melanoma Invasion

Melanoma is one of the most aggressive cancers affecting humans. Although early melanomas are curable with surgical excision, metastatic melanomas are associated with high mortality. The mechanism of melanoma development, progression, and metastasis is largely unknown. In order to uncover genes unique to melanoma cells, we used high-density DNA microarrays to examine the gene expression profiles of metastatic melanoma nodules using benign nevi as controls. Over 190 genes were significantly overexpressed in metastatic melanomas compared with normal nevi by at least 2-fold. One of the most abundantly expressed genes in metastatic melanoma nodules is osteopontin (OPN). Immunohistochemistry staining on tissue microarrays and individual skin biopsies representing different stages of melanoma progression revealed that OPN expression is first acquired at the step of melanoma tissue invasion. In addition, blocking of OPN expression by RNA interference reduced melanoma cell numbers in vitro. Our observations suggest that OPN may be acquired early in melanoma development and progression, and may enhance tumor cell growth in invasive melanoma.

Osteopontin involvement in bone remodeling and its effects on in vivo osteogenic potential of bone marrow-derived osteoblasts/porous hydroxyapatite constructs

This review article will present our work regarding osteopontin (OPN) function in bone remodeling and its application to tissue engineering in bone. OPN, one of the major non-collagenous bone proteins, has an important role in bone remodeling. Our study suggested that OPN acts not only as a trigger for osteoblast early differentiation but activates osteoclast resorption. On this point of view, we proposed a model of bone remodeling via integrin α Vβ 3–OPN binding, in which OPN could act as a signal molecule between osteoblasts and osteoclasts in the process of remodeling. Moreover, OPN was shown to induce the in vivo osteogenesis of a bone marrow-derived osteoblast/porous hydroxyapatite (HA) constructs. Our application of adenovirus-mediated gene transfer of osteopontin to primary osteoblasts is also presented.

Enhanced expression of osteopontin by high glucose: Involvement of osteopontin in diabetic vascular diseases

Enhanced expression of osteopontin by high glucose: Involvement of osteopontin in diabetic vascular diseases

Enhanced expression of osteopontin by high glucose. Involvement of osteopontin in diabetic macroangiopathy.

Atherosclerotic vascular disease is a major complication of diabetic patients. Osteopontin has recently been implicated in the development of atherosclerosis. In the present study, we have investigated the effects of high glucose on expression of osteopontin in cultured rat aortic smooth muscle cells. High concentrations of glucose increased osteopontin secretion from the cells, and the increased secretion was completely inhibited by an inhibitor of protein kinase C, GF109203X. Northern blot analysis confirmed the enhanced effect of glucose on expression of osteopontin mRNA. Promoter activity of osteopontin, measured using the osteopontin promoter/luciferase expression vector system, was increased by high glucose, and the enhanced effect was completely inhibited by GF109203X. Glucosamine also increased the promoter activity of osteopontin. Azaserine, an inhibitor of glutamine:fructose-6-phosphate amidotransferase, the key enzyme of the hexosamine pathway, profoundly inhibited high glucose-mediated increase in the promoter activity. Taken together, these data indicate that high glucose enhances the expression of osteopontin at the transcriptional level possibly through the activation of protein kinase C as well as the hexosamine pathway. Our results suggest that osteopontin could play a role in the development of diabetic vascular complications.