The Biology of Small Leucine-rich Proteoglycans in Bone Pathophysiology

Nikitovic, Dragana; Aggelidakis, John; Young, Marian F.; Iozzo, Renato V.; Karamanos, Nikos K.; Tzanakakis, George N.

doi:10.1074/jbc.r112.379602

Cited by 134 publications

(131 citation statements)

References 91 publications

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“…27 Both Decorin and Biglycan belong to class I SLRPs and only differ in the number of glycosaminoglycans around the protein core where Decorin carries single chondroitin sulphate/dermatan sulphate and Biglycan carries two chondroitin sulphate/ dermatan sulphate. 28 Lumican is another member classified under class II SLRPs. It consists of four keratan sulphate bound to the LRR.…”

Section: Introductionmentioning

confidence: 99%

Altered expression of small leucine-rich proteoglycans (Decorin, Biglycan and Lumican): Plausible diagnostic marker in urothelial carcinoma of bladder

et al. 2017

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Small leucine-rich proteoglycans are components of extracellular matrix that regulates neoplastic transformation. Among small leucine rich proteoglycans, Decorin, Biglycan and Lumican are most commonly implicated markers, and their expression is well studied in various malignancies. In this novel study, we have collectively evaluated expression of these three molecules in urothelial carcinoma of bladder. Thirty patients of confirmed untreated bladder cancer, 30 healthy controls for blood and 30 controls for adjacent non-tumour tissue were enrolled. Blood was collected from all subjects and tumour/adjacent normal tissue was obtained from the patients. Circulatory levels were estimated by enzyme-linked immunosorbent assay, relative messenger RNA expression by quantitative polymerase chain reaction and protein expression by immunohistochemistry and western-blotting. Circulatory levels of Biglycan (p = 0.0038) and Lumican (p < 0.0001) were significantly elevated, and that of Decorin (p < 0.0001) was significantly reduced in patients as compared with controls. Protein expression by immunohistochemistry and western-blotting showed elevated expression of Lumican and Biglycan and lower expression of Decorin in urothelial carcinoma of bladder. Quantitative polymerase chain reaction for messenger RNA expression from tissue specimens revealed significantly higher expression of Biglycan (p = 0.0008) and Lumican (p = 0.01) and lower expression of Decorin (p < 0.0001) in urothelial carcinoma of bladder. Out of all molecules receiver operating characteristic curve showed that the 0.207 ng/ml cut-off of serum Lumican provided optimum sensitivity (90.0%) and specificity (90.0%). Significant alteration of matrix small leucine-rich proteoglycans in urothelial carcinoma of bladder was observed. Higher expression of Lumican in Bladder cancer patients with the cut-off value of highest optimum sensitivity and specificity shows its importance as a potential non-invasive marker for early detection of UBC following further validation in large patient cohort.

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Section: Introductionmentioning

confidence: 99%

Altered expression of small leucine-rich proteoglycans (Decorin, Biglycan and Lumican): Plausible diagnostic marker in urothelial carcinoma of bladder

et al. 2017

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“…DS-biglycan is expressed in early stages of bone formation, ceases during early matrix deposition and is re-expressed at the onset of mineralisation as CS-biglycan [42][43][44][45]. Decorin is expressed later in osteogenesis and is associated with early matrix deposition and the mineralisation phases of bone development [46,47]. DS-substituted decorin is associated with early bone development but the CS form predominates during mineralisation.…”

Section: Discussionmentioning

confidence: 99%

The 7D4, 4C3 and 3B3 (-) Chondroitin Sulphation Motifs are expressed at Sites of Cartilage and Bone Morphogenesis during Foetal Human Knee Joint Development

Melrose¹,

Smith²

2016

J Glycobiol

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Novel sulphation motifs within the glycosaminoglycan (GAG) chain structure of chondroitin sulphate (CS)-containing s are associated with sites of growth and differentiation in many biological systems where they function as molecular recognition sites involved in the binding, sequestration or presentation of soluble signalling molecules (e.g. growth factors, cytokines, morphogens). The specific sulphation motifs on CS identified by monoclonal antibodies 3-B-3(-), 4-C-3 and 7-D-4 are also associated with distinct cohorts of cells in areas of tissue morphogenesis in human foetal knee joint development. We hypothesize that such motifs may have roles to play in the regulation of proliferative/differentiative events during tissue morphogenesis. In the present investigation we have examined the distribution of these CS motifs within the rudiment cartilage, stromal connective tissues surrounding the rudiment cartilages and developing growth plates of the human foetal knee joint. These CS motifs had broad, overlapping distributions throughout the differentiating connective tissues undergoing morphogenesis and after joint cavitation were localised very specifically to the rudiment cartilage destined to form the permanent articular cartilage postnatally, and to the terminally differentiated chondrocytes and calcified cartilage-bone interface in the growth plate cartilages. The overlapping distributions of these molecules within the presumptive articular cartilage, prior to secondary ossification, suggests that they participate in early signalling events involved in tissue development and indicates that the cells within this zone are phenotypically distinct from those of the underlying rudiment cartilage.

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“…The hydration shell of collagen is provided by small proteoglycans SLRPs (Small Leucine-Rich Proteoglycans) that decorate the surface of collagen fibrils 61 . The precisely located, enzymatic covalent crosslinks in the collagenous scaffold confine bound water to the interfibrillar space 62 .…”

Section: Biomechanical Implications Of Inhibition and Promotion Of MImentioning

confidence: 99%

A materials science vision of extracellular matrix mineralization

et al. 2016

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From an engineering perspective, skeletal tissues are remarkable structures in that they are lightweight, stiff and tough, yet produced at ambient conditions. The biomechanical success of skeletal tissues is largely attributable to the process of biomineralization -a tightly regulated, cell-driven formation of billions of inorganic nanocrystals formed from ions found abundantly in body fluids. In this Review, we discuss nature's strategies to produce and sustain appropriate biomechanical properties in mineralizing (by promotion of mineralization) and nonmineralizing (by inhibition of mineralization) tissues. We review how perturbations of biomineralization are controlled over a continuum which spans from the desirable (or defective in disease) mineralization of the skeleton, to pathological cardiovascular mineralization, and to mineralization of bioengineered constructs. A materials science vision of mineralization is presented with an emphasis on the micro-and nanostructure of mineralized tissues recently revealed by state-of-the-art analytical methods, and on how biomineralization-inspired designs are impacting the field of synthetic materials. Web summaryComplex mechanisms are at play in the biomineralization of skeletal tissues and in patholological calcification in the cardiovascular system. In this Review, the physiochemical and biomechanical properties of mineralized tissues, both physiologic and pathophysiologic, and analytical methods to elucidate their finer structure are discussed.

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The Biology of Small Leucine-rich Proteoglycans in Bone Pathophysiology

Cited by 134 publications

References 91 publications

Altered expression of small leucine-rich proteoglycans (Decorin, Biglycan and Lumican): Plausible diagnostic marker in urothelial carcinoma of bladder

Altered expression of small leucine-rich proteoglycans (Decorin, Biglycan and Lumican): Plausible diagnostic marker in urothelial carcinoma of bladder

The 7D4, 4C3 and 3B3 (-) Chondroitin Sulphation Motifs are expressed at Sites of Cartilage and Bone Morphogenesis during Foetal Human Knee Joint Development

A materials science vision of extracellular matrix mineralization

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