Immunolocation analysis of glycosaminoglycans in the human growth plate.

Byers, Sharon; Caterson, Bruce; Hopwood, John J.; Foster, Bruce K.

doi:10.1177/40.2.1372629

Cited by 46 publications

(31 citation statements)

References 5 publications

(6 reference statements)

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“…Within the growth plate, the hypertrophic zone is the most active region of aggrecan resorption. Aggrecan synthesized by hypertrophic chondrocytes has structural features that distinguish it from aggrecan synthesized in the proliferative and reserve zones (7,59). It has an increased hydrodynamic size due to increased glycosaminoglycan chain length, as well as an increased incidence of the G3 domain, indicative of a newly synthesized, full-length core protein (51).…”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinases Are Not Essential for Aggrecan Turnover during Normal Skeletal Growth and Development

Little

Meeker

Hembry

et al. 2005

Molecular and Cellular Biology

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The growth plate is a transitional region of cartilage and highly diversified chondrocytes that controls long bone formation. The composition of growth plate cartilage changes markedly from the epiphysis to the metaphysis, notably with the loss of type II collagen, concomitant with an increase in MMP-13; type X collagen; and the C-propeptide of type II collagen. In contrast, the fate of aggrecan in the growth plate is not clear: there is biosynthesis and loss of aggrecan from hypertrophic cartilage, but the mechanism of loss is unknown. All matrix metalloproteinases (MMPs) cleave aggrecan between amino acids N 341 and F 342 in the proteinase-sensitive interglobular domain (IGD), and MMPs in the growth plate are thought to have a role in aggrecanolysis. We have generated mice with aggrecan resistant to proteolysis by MMPs in the IGD and found that the mice develop normally with no skeletal deformities. The mutant mice do not accumulate aggrecan, and there is no significant compensatory proteolysis occurring at alternate sites in the IGD. Our studies reveal that MMP cleavage in this key region is not a predominant mechanism for removing aggrecan from growth plate cartilage.Endochondral ossification is the process by which bone is formed upon a cartilage template. It occurs in skeletal development, in fracture healing, and during bone growth at the growth plates and involves the transition from avascular cartilage, rich in type II collagen and aggrecan, to highly vascular bone, rich in type I collagen and mineral. During endochondral bone formation, prechondrogenic mesenchymal cells differentiate into chondrocytes, which proliferate and then mature into hypertrophic chondrocytes. The hypertrophic cartilage begins to calcify, the cartilage matrix is degraded and is invaded by blood vessels, the terminal hypertrophic chondrocytes apoptose, and bone matrix is deposited on the calcified cartilage trabeculae. This is a busy schedule of events in the growth plate, and their precise timing in relation to each other has not been clearly defined.The growth plate is a striking remodeling unit both anatomically and biochemically. Anatomically, it is bordered by the secondary center of ossification and epiphysis at one end and the bony metaphysis at the other. It comprises reserve, proliferative, prehypertrophic, and hypertrophic zones. Chondrocytes in the reserve zone are rounded and sparsely distributed, whereas chondrocytes in the proliferative zone are flattened and occupy approximately one-quarter of the tissue volume. Cells of the proliferative zone divide and arrange themselves into ordered columns separated by longitudinal septa. At the same time, they increase their secretion of matrix molecules so that around 75% of the tissue volume is cartilage matrix. In the hypertrophic zones, the cells retain their columnar organization and increase their metabolic activity. They enlarge by as much as 10-fold (28) so that matrix volume is reduced to approximately 40%, with cells occupying 60% of the tissue volume (5). Calcificat...

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Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinases Are Not Essential for Aggrecan Turnover during Normal Skeletal Growth and Development

Little

Meeker

Hembry

et al. 2005

Molecular and Cellular Biology

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“…Like changes in background fluorescence, collagen denaturation products were first detected in the upper mid region of the cartilage and The association of the proteoglycan epitopes 7D4 and 3B3-with activation of an immature chondrocyte phenotype in OA cartilage has been controversial. The immunodetection of these proteoglycan epitopes has been shown to be enhanced in immature articular cartilage [14] and growth cartilage [6,14] and also in OA articular cartilage [29] and in animal models of OA [7,30]. However, a recent chemical analysis of the 3B3-epitope failed to detect any substantial change in OA cartilage [26] and suggested instead that immunodetection of the 3B3-epitope is influenced by clustering or unmasking of existing proteoglycan structures.…”

Section: Discussionmentioning

confidence: 99%

“…Monoclonal antibody 7D4 recognizes a native glycosaminoglycan epitope that is composed of an as yet incompletely characterized disaccharide sequence [30,31]. The epitope appears to be concentrated near the Iinkage region of the chondroitin sulfate to the core protein of some aggrecan molecules [16,27,30] and is prominent in immature cartilage [6,14]. Monoclonal antibody 3B3 is an IgM that recognizes a disaccharide containing terminal unsaturated hexuronate adjacent to Nacetylgalactosamine 6 sulfate generated by chondroitinase digestion [8].…”

Section: Antibodiesmentioning

confidence: 99%

“…Monoclonal antibody 3B3 is an IgM that recognizes a disaccharide containing terminal unsaturated hexuronate adjacent to Nacetylgalactosamine 6 sulfate generated by chondroitinase digestion [8]. A native mimitope of this epitope (3B3-) is expressed at the nonreducing terminal of some chondroitin sulfate glycosaminoglycans on aggrecan from OA cartilage and in the hypertrophic zone of the growth plate [6,14,29]. Monoclonal antibody TI-II6B3 specific for type I1 collagen was purchased from the Developmental Studies Hybridoma Bank, (Iowa City, IA).…”

Section: Antibodiesmentioning

confidence: 99%

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Degradation of the cartilage collagen matrix associated with changes in chondrocytes in osteoarthrosis. Assessment by loss of background fluorescence and immunodetection of matrix components

Gibson

Verner

Nelson

et al. 2001

Journal Orthopaedic Research

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Articular cartilage damage and eventual loss is the primary pathological change seen in osteoarthrosis (OA). In this study we have investigated the link between turnover of the collagen matrix and changes in chondrocytes. The background fluorescence of articular cartilage, as indicated by its emission spectrum and resistance to extraction was generated by the slow non-enzymic modification of the collagen matrix by advanced glycation end products (AGES). Assessment of changes in background fluorescence in sections of articular cartilage provided a narrative of collagen degradation. Patients without OA pathology typically had a uniform strong background fluorescence throughout the depth of the cartilage. Cartilage from OA patients showed a range of changes in background fluorescence dependent on depth from the articular surface and proximity to overt lesions. Loss of background fluorescence was centered on chondrocytes, more extensive near the surface and associated with detection of the proteoglycan epitope 7D4. Expression of type X collagen was seen in articular cartilage in the region of the interface of with subchondral bone in most OA patients but was not associated with prominent, pericellular, loss of background fluorescence. These observations are consistent with progressive cartilage damage in OA, whereby collagen turnover and loss of surface integrity is associated with chondrocyte activity similar to that seen in immature articular cartilage.

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“…The long-bone growth plate provides an opportunity to investigate the sequence of events that occur during the lifespan of chondrocytes and in cartilage matrix production (5). The epiphyseal growth plate continues to form new cartilage with renewal of chondrocytes, and consequently participates in the longitudinal growth of long bones (20).…”

Section: Introductionmentioning

confidence: 99%

In vivo modulation of proliferating cell nuclear antigen in growth plate chondrocytes from normal, hypophysectomized, growth hormone-treated hypophysectomized rats: a comparative immunohistochemical study with image analysis.

Tajima¹,

Kato²,

Maruyama³

et al. 1996

J Histochem Cytochem.

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Growth hormone (GH) regulates the proliferation and maturation of chondrocytes in the epiphyseal growth plate, in which a temporal dimension is superimposed on the septal organization of the tissue. In this study we investigated the in vivo effects of hypophysectomy (Hypox) and injection of GH into Hypox animals (Hypox + GH) on the proliferative activity of the growth plate chondrocytes. We assessed the immunohistochemical expression of proliferating cell nudear antigen (PCNA) in pataffi-embedded tissues, using monoclonal antibody PC 10 against PCNA combined with immunogold-silver staining. We subjected the immunostained sections to computer-based image analysis by ACAS 570 interactive laser cytometry employing a conventional microscopic light source. Hypox was carried out on 20 rats at 8 weeks of age, half of which received a hypodermic injection of human GH at a dose of 1 IUlkg twice a day for 1 week after the operation. Another group of five rats of the same age were used as normal controls. In normal rats, a distinct PCNA immunoreaction was observed in the proliferative IntroductionThe long-bone growth plate provides an opportunity to investigate the sequence of events that occur during the lifespan of chondrocytes and in cartilage matrix production (5). The epiphyseal growth plate continues to form new cartilage with renewal of chondrocytes, and consequently participates in the longitudinal growth of long bones (20). The growth plate itself consists of several morphologi-'

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Immunolocation analysis of glycosaminoglycans in the human growth plate.

Cited by 46 publications

References 5 publications

Matrix Metalloproteinases Are Not Essential for Aggrecan Turnover during Normal Skeletal Growth and Development

Matrix Metalloproteinases Are Not Essential for Aggrecan Turnover during Normal Skeletal Growth and Development

Degradation of the cartilage collagen matrix associated with changes in chondrocytes in osteoarthrosis. Assessment by loss of background fluorescence and immunodetection of matrix components

In vivo modulation of proliferating cell nuclear antigen in growth plate chondrocytes from normal, hypophysectomized, growth hormone-treated hypophysectomized rats: a comparative immunohistochemical study with image analysis.

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