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In recent decades, evidence has accumulated implicating heparan sulfate proteoglycans (HSPGs) in tumor initiation and progression. Ubiquitously present at the cell surface and in the extracellular matrix, HSPGs are composed of a protein core with covalently bound heparan sulfate (HS) chains. They present high structural complexity and heterogeneity provided by the coordinated action of several biosynthetic and HS modifying enzymes in a tissue - and cell type-specific manner. The absence of HS is incompatible with life, highlighting the critical role of HS and HSPGs in key physiological processes including cell adhesion, migration, invasion as well as cell signaling. The essential contribution of HSPGs to these processes depends on the ability of HS to bind hundreds of proteins and to modulate their activity. This unique property allows HSPGs to exert multiple functions either structural, by conferring integrity and insolubility to the extracellular matrix, or functional, by regulating bioavailability and signaling of growth factors and cytokines. Shedding of the core protein by proteases and degradation of HS by the endoglycosidase heparanase, which produce bioactive molecules, further extends and adds complexity to the biological functions of HSPGs. Altered expression or deregulated function of HSPGs, or of their biosynthetic/modifying enzymes, has been reported in several tumor types and a vast literature supports their participation in inflammation, tumor growth, angiogenesis and metastasis. Moreover, heparanase and enzymes that edit regulate the sulfation pattern of HS, endosulfatases and sulfotransferases, have emerged as players able to influence the response of tumors to therapy. HSPGs and HS modifying enzymes have attracted much interest as potential biomarkers and antitumor therapeutic targets, supported by promising preclinical studies. Several biological and pharmacological targeting approaches are under intensive investigation. Currently, however, only a few early clinical trials include HS mimetics or heparanase inhibitors, HSPG-directed monoclonal antibody and peptide vaccine, or are testing HSPGs as a candidate tumor biomarker. A deeper insight into the roles of HSPGs and related enzymes in the pathogenesis and progression of specific tumor types and sub-types is expected to favor the transilation of preclinical studies to the clinic. In this Research Topic, we collect articles highlighting the pathological role of HSPGs and HS modifying enzymes in specific tumor contexts, elucidating their pleiotropic effects and investigating their biomarker and target significance, with the aim of fully exploiting their potential value in diagnosis, prognosis and treatment using novel therapeutic approaches.

heparan sulfate proteoglycan --- heparanase --- sulfotransferase --- glypican --- cancer therapy

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Osteomodulin (OMD) is a proteoglycan of the SLRP (Small leucine-rich repeat proteoglycans) family. This protein is specifically expressed in mineralised tissue. Like other SLRPs, OMD is involved in the organisation of the ECM. Little is known about the functions of OMD and its involvement in the organisation of the bone matrix. The study of osteomodulin takes place in the context of osteoarthritis. Osteoarthritis is a complex disease which is characterised by a large number of phenotypes involving the different elements of a joint such as the articular cartilage, the subchondral bone or the synovium. The underlying molecular mechanisms of this disease are not yet well defined. The expression of OMD is reduced in osteoblasts from osteoarthritis patients and a better understanding of the activity of this protein in bone could therefore help to understand its involvement in bone-driven osteoarthritis. Studies of non-sclerotic osteoblast cultures have shown a slight increase in alkaline phosphatase activity when treated with OMD. The functions of omd have also been studied in the zebrafish. The zebrafish model is widely used to study skeletal physiology and pathology. Injection of omd mRNA develops significant ventralization and skeletal malformation phenotypes in this model. These results suggest that OMD may regulate the activity of morphogens including BMP2 in the bone and/or cartilage ECM. L’ostéomoduline (OMD) est un protéoglycane de la famille des « small leucine-rich repeat proteoglycans » (SLRPs). Cette protéine est exprimée de manière spécifique dans les tissus minéralisés. Comme les autres SLRPs, l'OMD est impliqué dans l'organisation de la matrice extracellulaire (MEC). Les fonctions de l'OMD et son implication dans l'organisation de la matrice osseuse sont peu connues. L’étude de l’ostéomoduline s’inscrit dans le contexte de l’arthrose. L’arthrose est une maladie complexe qui est caractérisée par un grand nombre de phénotypes impliquant les différents éléments d’une articulation tels que le cartilage articulaire, l’os sous-chondral ou encore la synovie. Les mécanismes moléculaires sous-jacents de cette maladie ne sont pas encore bien définis. L’expression de l’OMD est réduite dans les ostéoblastes de patients arthrosiques et une meilleure compréhension de l’activité de cette protéine dans l’os pourrait donc permettre de comprendre son implication dans l’arthrose. L’étude de cultures d’ostéoblastes non-sclérotiques a permis de montrer une légère augmentation de l’activité de l’alcaline phosphatase lorsque celles-ci sont traitées à l’OMD. L’omd a également été étudiée chez le zebrafish. Le modèle de zebrafish est largement utilisé pour étudier la physiologie et la pathologie du squelette. L’injection d’ARNm d’omd développe dans ce modèle des phénotypes de ventralisations et de malformations du squelette importantes. Ces résultats suggèrent que l’OMD pourrait être un régulateur de l’activité des morphogènes dont BMP2 au niveau de la MEC osseuse et/ou cartilagineuse.

Zebrafish --- Osteomodulin --- Osteoblast --- Proteoglycan --- Bone --- Cartilage --- Ostéomoduline --- Os --- Cartilage --- Ostéoblaste --- Zebrafish --- Protéoglycane --- Sciences de la santé humaine > Rhumatologie

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L’arthrose est la pathologie dégénérative articulaire la plus fréquente. Elle touche à ce jour dix à quinze pour cent de la population adulte mondiale. Cette maladie, par sa prévalence en constante augmentation et l’absence de biomarqueur validé en routine, est classée par l’OMS parmi les pathologies prioritaires.
Précédemment, il a été mis en évidence une expression différentielle de l’ostéomoduline (OMD), une petite protéoglycane riche en leucines (SLRP), entre les ostéoblastes sains et les ostéoblastes dérivés d’os sclérotique en faisant ainsi un candidat biomarqueur pour le diagnostic et le suivi de la maladie.
Le but de ce mémoire était, d’une part, d’étudier, in vitro, les effets de l’OMD sur la capacité de minéralisation d’ostéoblastes dérivés d’os sous-chondral sclérotique et, d’autre part, d’évaluer les effets de la molécule sur le développement de l’arthrose chez la souris.
Il n’a pas été possible de mettre en évidence un effet de l’OMD sur la capacité de minéralisation des ostéoblastes. Cependant, les paramètres de démarche des souris transgéniques n’exprimant pas l’OMD étaient altérés, suggérant la présence de douleur lors de la marche.
Des investigations complémentaires, histologiques, permettront de déterminer si ces altérations sont la conséquence de la dégradation articulaire. Osteoarthritis is the most common degenerative joint disease. It currently affects ten to fifteen per cent of the adult population worldwide. Due to its constantly increasing prevalence and the absence of a validated routine biomarker, this condition is classified by the WHO as a priority disease.
Previously, differential expression of osteomodulin (OMD), a small leucine-rich proteoglycan (SLRP), between healthy and sclerotic bone-derived osteoblasts has been demonstrated, making it a candidate biomarker for the diagnosis and monitoring of the disease.
The aim of this master thesis was to study the effects of OMD on the mineralisation capacity of sclerotic subchondral bone-derived osteoblasts in vitro and to assess the effects of the molecule on the development of osteoarthritis in mice.
It was not possible to demonstrate an effect of OMD on the mineralisation capacity of osteoblasts. However, the gait parameters of transgenic mice not expressing OMD were impaired, suggesting the existence of pain during locomotion.
Further histological examinations will determine whether these alterations are the consequence of joint degradation.

ostéomoduline --- ostéoadhérine --- arthrose --- biomarqueur --- catwalk --- osteoblaste --- protéoglycane --- histologie --- os sous-chondral --- os --- cartilage --- osteomodulin --- osteoadherin --- osteoarthritis --- biomarker --- catwalk --- osteoblast --- proteoglycan --- slrp --- histology --- subchondral bone --- bone --- cartilage --- Sciences de la santé humaine > Rhumatologie

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This Special Issue covers original and innovative basic research regarding the anti-inflammatory potential of several classes of secondary metabolites (i.e., polyphenols, phytosterols, proteoglycans, and polysaccharides) in manifestations of acute and chronic inflammation in both in vitro and in vivo experimental models.

laminarin --- aging --- transient cerebral ischemia --- neuroprotection --- oxidative stress --- neuroinflammation --- marine-derived fungi --- anti-inflammation --- anti-neuroinflammation --- PTP1B --- marine biocompounds --- neurodegeneration --- Alzheimer’s disease --- Parkinson’s disease --- Bacillus sp. --- proteoglycan --- macrophages --- Padina boryana --- RAW 264.7 macrophages --- Nrf2/HO-1 --- MAPK --- NF-κB --- P. oceanica --- inflammation --- pain --- CD-1 mice

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This book provides a state-of-the-art compendium on the role of proteoglycans and glycosaminoglycans during development and in cancer. It also suggests directions for novel therapeutic and biotechnological applications in stem cell biology. Proteoglycans and glycosaminoglycans, as part of the extracellular matrix, are multifunctional modulators of growth factor, cytokine, integrin and morphogen signaling, which determine both self-renewal, senescence and/or differentiation of stem cells during development. Since proteoglycans modulate cell adhesion and migration they are important organizers of the extracellular matrix within the proper stem cell niche. A malfunctioning of proteoglycans and glycosaminoglycans contributes to the cancer stem cell phenotype, which is linked to therapeutic resistance and recurrence in malignant disease. This book is essential reading for anyone interested in the extracellular matrix and its role in development. The series Biology of Extracellular Matrix is published in collaboration with the American Society for Matrix Biology.

Developmental biology. --- Cancer research. --- Human physiology. --- Analytical chemistry. --- Developmental Biology. --- Cancer Research. --- Human Physiology. --- Analytical Chemistry. --- Analysis, Chemical --- Analytic chemistry --- Chemical analysis --- Chemistry, Analytic --- Chemistry --- Human biology --- Medical sciences --- Physiology --- Human body --- Cancer research --- Development (Biology) --- Biology --- Growth --- Ontogeny --- Proteoglycans. --- Glycosaminoglycans. --- Stem cells. --- Colony-forming units (Cells) --- Mother cells --- Progenitor cells --- Cells --- Mucopolysaccharides --- Glycoproteins --- Stem Cells. --- Proteoglycans --- Proteoglycan --- Proteoglycan Type H --- Colony-Forming Unit --- Colony-Forming Units --- Mother Cells --- Progenitor Cells --- Cell, Mother --- Cell, Progenitor --- Cell, Stem --- Cells, Mother --- Cells, Progenitor --- Cells, Stem --- Colony Forming Unit --- Colony Forming Units --- Mother Cell --- Progenitor Cell --- Stem Cell --- Cell Self Renewal --- Stem Cell Research --- Glicoproteïnes --- Biomolècules --- Cèl·lules mare --- Cèl·lules --- Cèl·lules mare embrionàries --- Molècules biològiques --- Molècules --- Àcids nucleics --- Biopolímers --- Metabòlits --- Proteïnes --- Biologia molecular --- Glucoprotèids --- Glucoproteïnes --- Glicoconjugats --- Antígens CD --- Integrines --- Interferó --- Laminina --- Mucoproteïnes