Perlecan Immunolocalizes to Perichondrial Vessels and Canals in Human Fetal Cartilaginous Primordia in Early Vascular and Matrix Remodeling Events Associated with Diarthrodial Joint Development

Melrose, James; Smith, Susan; Whitelock, John M.

doi:10.1369/jhc.4a6261.2004

Cited by 29 publications

(33 citation statements)

References 62 publications

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“…This implies that at the metaphyseal COJ, essentially no barriers for exiting endothelial lumina based on molecular size exist, or if they exist, they reside in the macromolecular structure and composition of the growth plate extracellular matrix. Second, recent experiments indicate that perlecan is found in epiphyseal and perichondrial vessels of growing long bones, but not in metaphyseal vessels (Melrose et al, 2004). This provides evidence supporting unique structural differences of metaphyseal vessels, compared to vessels of either the perichondrium or the epiphysis, which may have a role in the differential selective permeability of these vessel systems to molecules of different sizes.…”

Section: Biomolecular Size Exclusion Of Dextrans Equal To or Greater mentioning

confidence: 86%

In vivo delivery of fluoresceinated dextrans to the murine growth plate: Imaging of three vascular routes by multiphoton microscopy

et al. 2005

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Bone elongation by endochondral ossification occurs through the differentiation cascade of chondrocytes of cartilaginous growth plates. Molecules from the systemic vasculature reach the growth plate from three different directions: epiphyseal, metaphyseal, and a ring vessel and plexus associated with the perichondrium. This study is an analysis of the real-time dynamics of entrance of fluoresceinated tracers of different molecular weights into the growth plate from the systemic vasculature and tests the hypothesis that molecular weight is a key variable in the determination of both the directionality and the extent of tracer movement into the growth plate. Multiphoton microscopy was used for direct in vivo imaging of the murine proximal tibial growth plate in anesthetized 4-to 5-week-old transgenic mice with green fluorescent protein linked to the collagen II promoter. Mice were given an intracardiac injection of either fluorescein (332.3 Da) or fluoresceinated dextrans of 3, 10, 40, 70 kDa, singly or sequentially. For each tracer, directionality and rate of arrival, together with extent of movement within the growth plate, were imaged in real time. For small molecules (up to 10 kDa), vascular access from all three directions was observed and entrance was equally permissive from the metaphyseal and the epiphyseal sides. Within our detection limit (a few percent of vascular concentration), 40 kDa and larger dextrans did not enter. These results have implications both for understanding systemic and paracrine regulation of growth plate chondrocytic differentiation, as well as variables associated with effective drug delivery to growth plate chondrocytes. Key words: growth plate; vasculature; multiphoton microscopy; endochondral ossificationBone elongation in children occurs by endochondral ossification in cartilaginous growth plates at the ends of long bones. Chondrocytic differentiation in the growth plate begins with clonal expansion of stem cells, continues during cellular proliferation, and ends with cellular enlargement, followed by death and replacement by bone. The kinetics of chondrocytic activity in each stage and of the regulatory transitions between them determine the rate of bone elongation achieved. As in any cellular growth system, nutrients are required to sustain the process, and multiple endocrine and paracrine inputs regulate at each stage. For growth plate cartilage, the role of the extracellular matrix also must be considered, not only as a substantive contributor to elongation per se, but through its potential role as a communication link among chondrocytes of the growth plate, and between growth plate chondrocytes and cells of surrounding tissues such as the peri-

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Section: Biomolecular Size Exclusion Of Dextrans Equal To or Greater mentioning

confidence: 86%

In vivo delivery of fluoresceinated dextrans to the murine growth plate: Imaging of three vascular routes by multiphoton microscopy

et al. 2005

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“…(45) F: Total anionic proteoglycan (toluidine blue stain) in a 12-week foetal human elbow cartilaginous rudiment. G: Perlecan expression evident in the rudiment and associated vessel networks in the presumptive articulating surface regions of the elbow joint.…”

Section: Perlecan and Early Cartilage Developmentmentioning

confidence: 99%

Perlecan, the “jack of all trades” proteoglycan of cartilaginous weight‐bearing connective tissues

et al. 2008

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Perlecan is a ubiquitous proteoglycan of basement membrane and vascularized tissues but is also present in articular cartilage, meniscus and intervertebral disc, which are devoid of basement membrane and predominantly avascular. It is a prominent pericellular proteoglycan in the transitory matrix of the cartilaginous rudiments that develop into components of diarthrodial joints and the axial skeleton, and it forms intricate perichondrial vessel networks that define the presumptive articulating surfaces of developing joints and line the cartilage canals in cartilaginous rudiments. Such vessels have roles in the nutrition of the expanding cell numbers in the developing joint. Perlecan sequesters a number of growth factors pericellularly (FGFs, PDGF, VEGF and CTGF) and through these promotes cell signalling, cell proliferation and differentiation. Perlecan also interacts with a diverse range of extracellular matrix proteins, stabilising and organising the ECM, and promoting collagen fibrillogenesis. Perlecan is a prominent pericellular component of mesenchymal cells from their earliest developmental stages through to maturation, forming cell-cell and cell-ECM interconnections that are suggestive of a role in mechanosensory processes important to tissue homeostasis.

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“…Incubations with primary antibodies (Table 1) were performed using a Sequenza vertical cover-plate immunostaining system [32][33][34][35][36][37]. Endogenous peroxidase activity was blocked by incubating the tissue sections with 3% H 2 O 2 for 5 min, washed in water then non-specific binding sites were blocked with a serum free protein block (Dako x0909) or 10% swine serum for 10 min.…”

Section: Immunohistologymentioning

confidence: 99%

Aggrecan, versican and type VI collagen are components of annular translamellar crossbridges in the intervertebral disc

et al. 2007

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The aim of this study was to undertake a detailed analysis of the structure of the inter and intralamellar regions of the annulus fibrosus. A total of 30 newborn to 6 year-old lumbar ovine intervertebral discs (IVDs) were fixed and decalcified en-bloc to avoid differential swelling artifacts during processing and vertical midsagittal, and horizontal 4 lm sections were cut. These were stained with toluidine blue to visualise anionic proteoglycan (PG) species, H & E for cellular morphology and picrosirius red (viewed under polarized light) to examine collagenous organization. Immunolocalisations were also undertaken using anti-PG core-protein and glycosaminoglycan (GAG) side chain antibodies to native chondroitin sulphate (CS), D C-4-S and C-6-S unsaturated stubs generated by chondroitinase ABC digestion of CS, keratan sulphate (KS), and with antibodies to type I, II, VI, IX and X collagens. Trans-lamellar cross bridges (TLCBs), discontinuities in annular lamellae's which provide transverse interconnections, stained prominently with toluidine blue in the adult IVDs but less so in the newborn IVDs. In adult discs TLCBs were evident in both the posterior and anterior AF where they extended from the outermost annular lamellae almost to the transitional zone extending across as many as eight lamellar layers displaying a characteristic circuitous, meandering, serpentine type course. There were significantly fewer TLCBs in 2 week-old compared with skeletally mature sheep and there was a further increase from 2 to 6 years. Immunolocalisation of perlecan delineated blood vessels in the TLBs of the newborn but not adult IVDs extending into the mid AF. In contrast adult but not 2 week-old TLCBs were immunpositive for C-4-S, C-6-S, KS, aggrecan, versican and type VI collagen. The change in number and matrix components of the translamellar cross bridges with skeletal maturity and ageing suggest that they represent an adaptation to the complex biomechanical forces occurring in the annulus fibrosus.

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Perlecan Immunolocalizes to Perichondrial Vessels and Canals in Human Fetal Cartilaginous Primordia in Early Vascular and Matrix Remodeling Events Associated with Diarthrodial Joint Development

Cited by 29 publications

References 62 publications

In vivo delivery of fluoresceinated dextrans to the murine growth plate: Imaging of three vascular routes by multiphoton microscopy

In vivo delivery of fluoresceinated dextrans to the murine growth plate: Imaging of three vascular routes by multiphoton microscopy

Perlecan, the “jack of all trades” proteoglycan of cartilaginous weight‐bearing connective tissues

Aggrecan, versican and type VI collagen are components of annular translamellar crossbridges in the intervertebral disc

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