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Open AccessCommunication

Prevention of Initial Bacterial Attachment by Osteopontin and Other Bioactive Milk Proteins

by Mathilde Frost Kristensen, Esben Skipper Sørensen, Yumi Chokyu Del Rey and Sebastian Schlafer

Biomedicines 2022, 10(8), 1922; https://doi.org/10.3390/biomedicines10081922 - 09 Aug 2022

Cited by 3 | Viewed by 1770

A considerable body of work has studied the involvement of osteopontin (OPN) in human physiology and pathology, but comparably little is known about the interaction of OPN with prokaryotic cells. Recently, bovine milk OPN has been proposed as a therapeutic agent to prevent [...] Read more.

A considerable body of work has studied the involvement of osteopontin (OPN) in human physiology and pathology, but comparably little is known about the interaction of OPN with prokaryotic cells. Recently, bovine milk OPN has been proposed as a therapeutic agent to prevent the build-up of dental biofilms, which are responsible for the development of caries lesions. Bioactive milk proteins are among the most exciting resources for caries control, as they hamper bacterial attachment to teeth without affecting microbial homeostasis in the mouth. The present work investigated the ability of OPN to prevent the adhesion of three dental biofilm-forming bacteria to saliva-coated surfaces under shear-controlled flow conditions in comparison with the major milk proteins α-lactalbumin, β-lactoglobulin, αs1-casein, β-casein and κ-casein, as well as crude milk protein. OPN was the most effective single protein to reduce the adhesion of Actinomyces naeslundii, Lactobacillus paracasei subsp. paracasei and Streptococcus mitis. β-casein and crude milk protein also had a pronounced effect on all three species, which suggests binding to different microbial surface structures rather than the blocking of a specific bacterial adhesin. Bioactive milk proteins show potential to delay harmful biofilm formation on teeth and hence the onset of biofilm-related oral disease. Full article

(This article belongs to the Special Issue 30 Years of OPN Milestones and Future Avenues)

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15 pages, 2389 KiB

Open AccessArticle

Osteopontin—A Potential Biomarker for IgA Nephropathy: Machine Learning Application

by Barbara Moszczuk, Natalia Krata, Witold Rudnicki, Bartosz Foroncewicz, Dominik Cysewski, Leszek Pączek, Beata Kaleta and Krzysztof Mucha

Biomedicines 2022, 10(4), 734; https://doi.org/10.3390/biomedicines10040734 - 22 Mar 2022

Cited by 1 | Viewed by 2281

Abstract

Many potential biomarkers in nephrology have been studied, but few are currently used in clinical practice. One is osteopontin (OPN). We compared urinary OPN concentrations in 80 participants: 67 patients with various biopsy-proven glomerulopathies (GNs)—immunoglobulin A nephropathy (IgAN, 29), membranous nephropathy (MN, 20) [...] Read more.

Many potential biomarkers in nephrology have been studied, but few are currently used in clinical practice. One is osteopontin (OPN). We compared urinary OPN concentrations in 80 participants: 67 patients with various biopsy-proven glomerulopathies (GNs)—immunoglobulin A nephropathy (IgAN, 29), membranous nephropathy (MN, 20) and lupus nephritis (LN, 18) and 13 with no GN. Follow-up included 48 participants. Machine learning was used to correlate OPN with other factors to classify patients by GN type. The resulting algorithm had an accuracy of 87% in differentiating IgAN from other GNs using urinary OPN levels only. A lesser effect for discriminating MN and LN was observed. However, the lower number of patients and the phenotypic heterogeneity of MN and LN might have affected those results. OPN was significantly higher in IgAN at baseline than in other GNs and therefore might be useful for identifying patients with IgAN. That observation did not apply to either patients with IgAN at follow-up or to patients with other GNs. OPN seems to be a valuable biomarker and should be validated in future studies. Machine learning is a powerful tool that, compared with traditional statistical methods, can be also applied to smaller datasets. Full article

(This article belongs to the Special Issue 30 Years of OPN Milestones and Future Avenues)

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16 pages, 2624 KiB

Open AccessArticle

Inducible T-Cell Costimulator Ligand Plays a Dual Role in Melanoma Metastasis upon Binding to Osteopontin or Inducible T-Cell Costimulator

by Davide Raineri, Giuseppe Cappellano, Beatrice Vilardo, Federica Maione, Nausicaa Clemente, Elena Canciani, Elena Boggio, Casimiro Luca Gigliotti, Chiara Monge, Chiara Dianzani, Renzo Boldorini, Umberto Dianzani and Annalisa Chiocchetti

Biomedicines 2022, 10(1), 51; https://doi.org/10.3390/biomedicines10010051 - 27 Dec 2021

Cited by 7 | Viewed by 2631

Abstract

Recently, we demonstrated that inducible T-cell costimulator (ICOS) shares its unique ligand (ICOSL) with osteopontin (OPN), and OPN/ICOSL binding promotes tumor metastasis and angiogenesis in the 4T1 breast cancer model. Literature showed that OPN promotes melanoma metastasis by suppressing T-cell activation and recruiting [...] Read more.

Recently, we demonstrated that inducible T-cell costimulator (ICOS) shares its unique ligand (ICOSL) with osteopontin (OPN), and OPN/ICOSL binding promotes tumor metastasis and angiogenesis in the 4T1 breast cancer model. Literature showed that OPN promotes melanoma metastasis by suppressing T-cell activation and recruiting myeloid suppressor cells (MDSC). On the opposite, ICOS/ICOSL interaction usually sustains an antitumor response. Here, we engineered murine B16F10 melanoma cells, by transfecting or silencing ICOSL. In vitro data showed that loss of ICOSL favors anchorage-independent growth and induces more metastases in vivo, compared to ICOSL expressing cells. To dissect individual roles of the three molecules, we compared data from C57BL/6 with those from OPN-KO, ICOS-KO, and ICOSL-KO mice, missing one partner at a time. We found that OPN produced by the tumor microenvironment (TME) favors the metastasis by interacting with stromal ICOSL. This activity is dominantly inhibited by ICOS expressed on TME by promoting Treg expansion. Importantly, we also show that OPN and ICOSL highly interact in human melanoma metastases compared to primary tumors. Interfering with this binding may be explored in immunotherapy either for nonresponding or patients resistant to conventional therapies. Full article

(This article belongs to the Special Issue 30 Years of OPN Milestones and Future Avenues)

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13 pages, 858 KiB

Open AccessArticle

Osteopontin Gene Polymorphisms Are Associated with Cardiovascular Risk Factors in Patients with Premature Coronary Artery Disease

by Nonanzit Pérez-Hernández, Rosalinda Posadas-Sánchez, Gilberto Vargas-Alarcón, Lizet Paola Hernández-Germán, Verónica Marusa Borgonio-Cuadra and José Manuel Rodríguez-Pérez

Biomedicines 2021, 9(11), 1600; https://doi.org/10.3390/biomedicines9111600 - 02 Nov 2021

Cited by 1 | Viewed by 1560

Abstract

Osteopontin (OPN) is considered a clinical predictor of cardiovascular disease. We aimed to evaluate the association of the OPN gene polymorphisms rs2728127 and rs11730582 with the development of premature coronary artery disease (pCAD), cardiovascular risk factors, and cardiometabolic parameters. We evaluated [...] Read more.

Osteopontin (OPN) is considered a clinical predictor of cardiovascular disease. We aimed to evaluate the association of the OPN gene polymorphisms rs2728127 and rs11730582 with the development of premature coronary artery disease (pCAD), cardiovascular risk factors, and cardiometabolic parameters. We evaluated 1142 patients with pCAD and 1073 controls. Both polymorphisms were determined by Taqman assays. Similar allele and genotype frequencies were observed in both groups; additionally, an association of these polymorphisms with CAD and cardiometabolic parameters was observed in both groups. In patients with pCAD, the rs11730582 was associated with a high risk of hypoadiponectinemia (OR = 1.300, P _additive = 0.003), low risk of hypertension (OR = 0.709, P _{codominant 1} = 0.030), and low risk of having high non-HDL cholesterol (OR = 0.637, P _additive = 0.038). In the control group, the rs2728127 was associated with a low risk of fatty liver (OR = 0.766, P _additive = 0.038); while the rs11730582 was associated with a low risk of hypoadiponectinemia (OR = 0.728, P _dominant = 0.022), and risk of having elevated apolipoprotein B (OR = 1.400, P _dominant = 0.031). Our results suggest that in Mexican individuals, the rs11730582 and rs2728127 OPN gene polymorphisms are associated with some abnormal metabolic variables in patients with pCAD and controls. Full article

(This article belongs to the Special Issue 30 Years of OPN Milestones and Future Avenues)

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9 pages, 522 KiB

Open AccessArticle

Strong Associations between Plasma Osteopontin and Several Inflammatory Chemokines, Cytokines, and Growth Factors

by Anders Larsson, Johanna Helmersson-Karlqvist, Lars Lind, Johan Ärnlöv and Tobias Rudholm Feldreich

Biomedicines 2021, 9(8), 908; https://doi.org/10.3390/biomedicines9080908 - 28 Jul 2021

Cited by 1 | Viewed by 1630

Abstract

Osteopontin is a member of the proinflammatory cytokine network, a complex system that involves many chemokines, cytokines, and growth factors. The aim of the present study was to study the associations between osteopontin and a large number of chemokines, cytokines, and growth factors. [...] Read more.

Osteopontin is a member of the proinflammatory cytokine network, a complex system that involves many chemokines, cytokines, and growth factors. The aim of the present study was to study the associations between osteopontin and a large number of chemokines, cytokines, and growth factors. We analyzed plasma and urine osteopontin in 652 men from the Uppsala Longitudinal Study of Adult Men (ULSAM) study cohort and compared the levels with the levels of eighty-five chemokines, cytokines, and growth factors. We found significant associations between plasma osteopontin and 37 plasma biomarkers in a model adjusted for age, and 28 of those plasma biomarkers were significant in a model also adjusting for cardiovascular risk factors. There were no significant associations after Bonferroni adjustment between urine osteopontin and any of the studied plasma cytokine biomarkers. This study shows that circulating osteopontin participates in a protein–protein interaction network of chemokines, cytokines, and growth factors. The network contains responses, pathways, and receptor binding interactions relating to cytokines, regulation of the immune system, and also regulation of apoptosis and intracellular signal transduction. Full article

(This article belongs to the Special Issue 30 Years of OPN Milestones and Future Avenues)

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Review

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31 pages, 4172 KiB

Open AccessEditor’s ChoiceReview

The Role of Osteopontin in Microglia Biology: Current Concepts and Future Perspectives

by Dennis-Dominik Rosmus, Clemens Lange, Franziska Ludwig, Bahareh Ajami and Peter Wieghofer

Biomedicines 2022, 10(4), 840; https://doi.org/10.3390/biomedicines10040840 - 03 Apr 2022

Cited by 26 | Viewed by 10743

Abstract

The innate immune landscape of the central nervous system (CNS), including the brain and the retina, consists of different myeloid cell populations with distinct tasks to fulfill. Whereas the CNS borders harbor extraparenchymal CNS-associated macrophages whose main duty is to build up a [...] Read more.

The innate immune landscape of the central nervous system (CNS), including the brain and the retina, consists of different myeloid cell populations with distinct tasks to fulfill. Whereas the CNS borders harbor extraparenchymal CNS-associated macrophages whose main duty is to build up a defense against invading pathogens and other damaging factors from the periphery, the resident immune cells of the CNS parenchyma and the retina, microglia, are highly dynamic cells with a plethora of functions during homeostasis and disease. Therefore, microglia are constantly sensing their environment and closely interacting with surrounding cells, which is in part mediated by soluble factors. One of these factors is Osteopontin (OPN), a multifunctional protein that is produced by different cell types in the CNS, including microglia, and is upregulated in neurodegenerative and neuroinflammatory conditions. In this review, we discuss the current literature about the interaction between microglia and OPN in homeostasis and several disease entities, including multiple sclerosis (MS), Alzheimer’s and cerebrovascular diseases (AD, CVD), amyotrophic lateral sclerosis (ALS), age-related macular degeneration (AMD) and diabetic retinopathy (DR), in the context of the molecular pathways involved in OPN signaling shaping the function of microglia. As nearly all CNS diseases are characterized by pathological alterations in microglial cells, accompanied by the disturbance of the homeostatic microglia phenotype, the emergence of disease-associated microglia (DAM) states and their interplay with factors shaping the DAM-signature, such as OPN, is of great interest for therapeutical interventions in the future. Full article

(This article belongs to the Special Issue 30 Years of OPN Milestones and Future Avenues)

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17 pages, 9038 KiB

Open AccessReview

Osteopontin Expression in Thyroid Cancer: Deciphering EMT-Related Molecular Mechanisms

by Bruna Prunes Pena Baroni Viana, Amanda Vitória Pampolha Gomes, Etel Rodrigues Pereira Gimba and Luciana Bueno Ferreira

Biomedicines 2021, 9(10), 1372; https://doi.org/10.3390/biomedicines9101372 - 01 Oct 2021

Cited by 5 | Viewed by 2035

Abstract

Thyroid cancer is the most common tumor arising from the endocrine system and generally presents good prognosis. However, its aggressive subtypes are related to therapeutic resistance and early metastasis. Epithelial–mesenchymal transition (EMT) and its reverse process, the mesenchymal–epithelial transition (MET), are key events [...] Read more.

Thyroid cancer is the most common tumor arising from the endocrine system and generally presents good prognosis. However, its aggressive subtypes are related to therapeutic resistance and early metastasis. Epithelial–mesenchymal transition (EMT) and its reverse process, the mesenchymal–epithelial transition (MET), are key events mediating cancer progression, including in thyroid cancer. The matricellular protein osteopontin (OPN) has been reported as a master regulator of EMT in many tumor types. Although high OPN expression has been described and associated with important aspects of thyroid cancer progression, there is no clear evidence regarding OPN as a regulator of EMT in thyroid cancer. Thus, taking together the known roles of OPN in the modulation of EMT in cancer and the information reporting the expression of OPN in thyroid tumor progression, this review aims at summarizing and discussing data related to EMT in thyroid cancer and its putative relation to the roles of OPN in the development of thyroid cancer. These data provide new insights into the molecular mechanisms by which OPN could potentially modulate EMT in thyroid tumors, generating evidence for future studies that may contribute to new therapeutic, prognostic and/or diagnostic tools. Full article

(This article belongs to the Special Issue 30 Years of OPN Milestones and Future Avenues)

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28 pages, 2217 KiB

Open AccessReview

Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases

by Toshio Hattori, Hiroko Iwasaki-Hozumi, Gaowa Bai, Haorile Chagan-Yasutan, Ashwnini Shete, Elizabeth Freda Telan, Atsushi Takahashi, Yugo Ashino and Takashi Matsuba

Biomedicines 2021, 9(8), 1006; https://doi.org/10.3390/biomedicines9081006 - 13 Aug 2021

Cited by 15 | Viewed by 3219

Abstract

Circulating full-length osteopontin (FL-OPN) is elevated in plasma from patients with various infectious diseases, such as adult T-cell leukemia, Mycobacterium tuberculosis (TB), hepatitis virus infection, leptospirosis, acquired immune deficiency syndrome (AIDS), AIDS/TB, and coronavirus disease 2019 (COVID-19). Proteolysis of OPN by thrombin, matrix [...] Read more.

Circulating full-length osteopontin (FL-OPN) is elevated in plasma from patients with various infectious diseases, such as adult T-cell leukemia, Mycobacterium tuberculosis (TB), hepatitis virus infection, leptospirosis, acquired immune deficiency syndrome (AIDS), AIDS/TB, and coronavirus disease 2019 (COVID-19). Proteolysis of OPN by thrombin, matrix metalloproteases, caspase 8/3, cathepsin D, plasmin, and enterokinase generates various cleaved OPNs with a variety of bioactivities by binding to different target cells. Moreover, OPN is susceptible to gradual proteolysis. During inflammation, one of the cleaved fragments, N-terminal thrombin-cleaved OPN (trOPN or OPN-Arg¹⁶⁸ [OPN-R]), induces dendritic cell (DC) adhesion. Further cleavage by carboxypeptidase B2 or carboxypeptidase N removes Arg¹⁶⁸ from OPN-R to OPN-Leu¹⁶⁷ (OPN-L). Consequently, OPN-L decreases DC adhesion. In particular, the differences in plasma level over time are observed between FL-OPN and its cleaved OPNs during inflammation. We found that the undefined OPN levels (mixture of FL-OPN and cleaved OPN) were elevated in plasma and reflected the pathology of TB and COVID-19 rather than FL-OPN. These infections are associated with elevated levels of various proteases. Inhibition of the cleavage or the activities of cleaved products may improve the outcome of the therapy. Research on the metabolism of OPN is expected to create new therapies against infectious diseases. Full article

(This article belongs to the Special Issue 30 Years of OPN Milestones and Future Avenues)

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