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Special Issue "30 Years of OPN Milestones and Future Avenues 2.0"

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 August 2023 | Viewed by 3886

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Dr. Giuseppe Cappellano

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Department of Health Sciences, Center for Translational Research on Autoimmune and Allergic Disease-CAAD, Università del Piemonte Orientale, 28100 Novara, Italy
Interests: autoimmune diseases; liquid biopsy biomarkers; immunology; nanomaterial biocompatibility; flow cytometry; microvesicles
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Dear Colleagues,

This Commemorative Issue will collect all contributions pertaining the multifaceted roles of osteopontin (OPN), discovered 30 years ago. In the nineties, OPN was identified in human bone as an immobilized extracellular matrix protein, but since then, further studies have shown that OPN also acts as a soluble cytokine in body fluids, and it has been linked to various physiological and pathological processes. OPN mediates bone remodeling, macrophage response, cell migration and adhesion, inflammation and Th1 and Th17 cell differentiation. Moreover, OPN is involved in tumor angiogenesis and metastatic dissemination. To date, investigations have been based on the paradigm that molecular mediators of OPN functions are two classes of receptors, namely integrins and CD44. The recent finding of an additional cell receptor, i.e., ICOSL, opens a new scenario in which OPN may modulate the function of all of the cell types expressing ICOSL, and this interaction may be functionally modulated by ICOS.

Understanding how OPN is processed and interacts with its natural ligands is of paramount importance for elucidating the complex role that this protein plays in human diseases.

Herein, in this Commemorative Issue, authors are invited to review recent work or submit original studies in all areas of recent and current OPN research, with an emphasis on work providing molecular insight, including, but not limited to, novel physiological and pathological functions, or regulatory mechanisms.

Thus, let us stop counting OPN years and start making them count!

Dr. Giuseppe Cappellano
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

osteopontin
inflammation
autoimmunity
biomarker
cancer
therapeutics

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30 Years of OPN Milestones and Future Avenues in Biomedicines (8 articles)

Published Papers (5 papers)

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Research

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Open AccessArticle

Angiogenesis in the Outer Membrane of Chronic Subdural Hematomas through Thrombin-Cleaved Osteopontin and the Integrin α9 and Integrin β1 Signaling Pathways

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Biomedicines 2023, 11(5), 1440; https://doi.org/10.3390/biomedicines11051440 - 13 May 2023

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Abstract

Background: A chronic subdural hematoma (CSDH) is considered to be an inflammatory and angiogenic disease. The CSDH outer membrane, which contains inflammatory cells, plays an important role in CSDH development. Osteopontin (OPN) is an extracellular matrix protein that is cleaved by thrombin, generating the N-terminal half of OPN, which is prominently involved in integrin signal transduction. We explored the expression of the N-terminal half of OPN in CSDH fluid and the expression of integrins α9 and β1 and the downstream components of the angiogenic signaling pathways in the outer membrane of CSDHs. Methods: Twenty samples of CSDH fluid and eight samples of CSDH outer membrane were collected from patients suffering from CSDHs. The concentrations of the N-terminal half of OPN in CSDH fluid samples were measured using ELISA kits. The expression levels of integrins α9 and β1, vinculin, talin-1, focal adhesion kinase (FAK), paxillin, α-actin, Src and β-actin were examined by Western blot analysis. The expression levels of integrins α9 and β1, FAK and paxillin were also examined by immunohistochemistry. We investigated whether CSDH fluid could activate FAK in cultured endothelial cells in vitro. Results: The concentration of the N-terminal half of OPN in CSDH fluid was significantly higher than that in the serum. Western blot analysis confirmed the presence of these molecules. In addition, integrins α9 and β1, FAK and paxillin were localized in the endothelial cells of vessels within the CSDH outer membrane. FAK was significantly phosphorylated immediately after treatment with CSDH fluid. Conclusion: Our data suggest that the N-terminal half of OPN in CSDH fluid promotes neovascularization in endothelial cells through integrins α9 and β1. The N-terminal half of OPN, which is part of the extracellular matrix, plays a critical role in the promotion of CSDHs. Full article

(This article belongs to the Special Issue 30 Years of OPN Milestones and Future Avenues 2.0)

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Open AccessArticle

Increased Circulating Osteopontin Levels Promote Primary Tumour Growth, but Do Not Induce Metastasis in Melanoma

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Biomedicines 2023, 11(4), 1038; https://doi.org/10.3390/biomedicines11041038 - 28 Mar 2023

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Abstract

Osteopontin (OPN) is a phosphoprotein with diverse functions in various physiological and pathological processes. OPN expression is increased in multiple cancers, and OPN within tumour tissue has been shown to promote key stages of cancer development. OPN levels are also elevated in the circulation of cancer patients, which in some cases has been correlated with enhanced metastatic propensity and poor prognosis. However, the precise impact of circulating OPN (cOPN) on tumour growth and progression remains insufficiently understood. To examine the role of cOPN, we used a melanoma model, in which we stably increased the levels of cOPN through adeno-associated virus-mediated transduction. We found that increased cOPN promoted the growth of primary tumours, but did not significantly alter the spontaneous metastasis of melanoma cells to the lymph nodes or lungs, despite an increase in the expression of multiple factors linked to tumour progression. To assess whether cOPN has a role at later stages of metastasis formation, we employed an experimental metastasis model, but again could not detect any increase in pulmonary metastasis in animals with elevated levels of cOPN. These results demonstrate that increased levels of OPN in the circulation play distinct roles during different stages of melanoma progression. Full article

(This article belongs to the Special Issue 30 Years of OPN Milestones and Future Avenues 2.0)

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Review

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Osteopontin in Pulmonary Hypertension

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Biomedicines 2023, 11(5), 1385; https://doi.org/10.3390/biomedicines11051385 - 07 May 2023

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Abstract

Pulmonary hypertension (PH) is a pathological condition with multifactorial etiology, which is characterized by elevated pulmonary arterial pressure and pulmonary vascular remodeling. The underlying pathogenetic mechanisms remain poorly understood. Accumulating clinical evidence suggests that circulating osteopontin may serve as a biomarker of PH progression, severity, and prognosis, as well as an indicator of maladaptive right ventricular remodeling and dysfunction. Moreover, preclinical studies in rodent models have implicated osteopontin in PH pathogenesis. Osteopontin modulates a plethora of cellular processes within the pulmonary vasculature, including cell proliferation, migration, apoptosis, extracellular matrix synthesis, and inflammation via binding to various receptors such as integrins and CD44. In this article, we provide a comprehensive overview of the current understanding of osteopontin regulation and its impact on pulmonary vascular remodeling, as well as consider research issues required for the development of therapeutics targeting osteopontin as a potential strategy for the management of PH. Full article

(This article belongs to the Special Issue 30 Years of OPN Milestones and Future Avenues 2.0)

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Open AccessReview

Osteopontin as a Biomarker in Chronic Kidney Disease

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Biomedicines 2023, 11(5), 1356; https://doi.org/10.3390/biomedicines11051356 - 04 May 2023

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Abstract

Osteopontin (OPN) is a ubiquitously expressed protein with a wide range of physiological functions, including roles in bone mineralization, immune regulation, and wound healing. OPN has been implicated in the pathogenesis of several forms of chronic kidney disease (CKD) where it promotes inflammation and fibrosis and regulates calcium and phosphate metabolism. OPN expression is increased in the kidneys, blood, and urine of patients with CKD, particularly in those with diabetic kidney disease and glomerulonephritis. The full-length OPN protein is cleaved by various proteases, including thrombin, matrix metalloproteinase (MMP)-3, MMP-7, cathepsin-D, and plasmin, producing N-terminal OPN (ntOPN), which may have more detrimental effects in CKD. Studies suggest that OPN may serve as a biomarker in CKD, and while more research is needed to fully evaluate and validate OPN and ntOPN as CKD biomarkers, the available evidence suggests that they are promising candidates for further investigation. Targeting OPN may be a potential treatment strategy. Several studies show that inhibition of OPN expression or activity can attenuate kidney injury and improve kidney function. In addition to its effects on kidney function, OPN has been linked to cardiovascular disease, which is a major cause of morbidity and mortality in patients with CKD. Full article

(This article belongs to the Special Issue 30 Years of OPN Milestones and Future Avenues 2.0)

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Open AccessReview

Osteopontin and Cancer: Insights into Its Role in Drug Resistance

Chengcheng Hao

Jane Lane

and

Wen G. Jiang

Biomedicines 2023, 11(1), 197; https://doi.org/10.3390/biomedicines11010197 - 12 Jan 2023

Cited by 2 | Viewed by 1049

Abstract

Cancer is one of the leading causes of mortality worldwide. Currently, drug resistance is the main obstacle in cancer treatments with the underlying mechanisms of drug resistance yet to be fully understood. Osteopontin (OPN) is a member of the integrin binding glycophosphoprotein family that is overexpressed in several tumour types. It is involved in drug transport, apoptosis, stemness, energy metabolism, and autophagy, which may contribute to drug resistance. Thus, understanding the role of OPN in cancer drug resistance could be important. This review describes the OPN-based mechanisms that might contribute to cancer drug resistance, demonstrating that OPN may be a viable target for cancer therapy to reduce drug resistance in sensitive tumours. Full article

(This article belongs to the Special Issue 30 Years of OPN Milestones and Future Avenues 2.0)

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