scholarly journals Expression of a Truncated, Kinase-Defective TGF-β Type II Receptor in Mouse Skeletal Tissue Promotes Terminal Chondrocyte Differentiation and Osteoarthritis

1997 ◽  
Vol 139 (2) ◽  
pp. 541-552 ◽  
Author(s):  
Rosa Serra ◽  
Mahlon Johnson ◽  
Ellen H. Filvaroff ◽  
James LaBorde ◽  
Daniel M. Sheehan ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Transgenic Mice ◽  
Growth Plate ◽  
Dominant Negative Mutant ◽  
Type I ◽  
Type Ii ◽  
Type X Collagen ◽  
Skeletal Tissue ◽  
Hypertrophic Cartilage ◽  
Growth Plate Cartilage

Members of the TGF-β superfamily are important regulators of skeletal development. TGF-βs signal through heteromeric type I and type II receptor serine/threonine kinases. When over-expressed, a cytoplasmically truncated type II receptor can compete with the endogenous receptors for complex formation, thereby acting as a dominant-negative mutant (DNIIR). To determine the role of TGF-βs in the development and maintenance of the skeleton, we have generated transgenic mice (MT-DNIIR-4 and -27) that express the DNIIR in skeletal tissue. DNIIR mRNA expression was localized to the periosteum/perichondrium, syno-vium, and articular cartilage. Lower levels of DNIIR mRNA were detected in growth plate cartilage. Transgenic mice frequently showed bifurcation of the xiphoid process and sternum. They also developed progressive skeletal degeneration, resulting by 4 to 8 mo of age in kyphoscoliosis and stiff and torqued joints. The histology of affected joints strongly resembled human osteo-arthritis. The articular surface was replaced by bone or hypertrophic cartilage as judged by the expression of type X collagen, a marker of hypertrophic cartilage normally absent from articular cartilage. The synovium was hyperplastic, and cartilaginous metaplasia was observed in the joint space. We then tested the hypothesis that TGF-β is required for normal differentiation of cartilage in vivo. By 4 and 8 wk of age, the level of type X collagen was increased in growth plate cartilage of transgenic mice relative to wild-type controls. Less proteoglycan staining was detected in the growth plate and articular cartilage matrix of transgenic mice. Mice that express DNIIR in skeletal tissue also demonstrated increased Indian hedgehog (IHH) expression. IHH is a secreted protein that is expressed in chondrocytes that are committed to becoming hypertrophic. It is thought to be involved in a feedback loop that signals through the periosteum/ perichondrium to inhibit cartilage differentiation. The data suggest that TGF-β may be critical for multifaceted maintenance of synovial joints. Loss of responsiveness to TGF-β promotes chondrocyte terminal differentiation and results in development of degenerative joint disease resembling osteoarthritis in humans.

Characterisation of articular and growth plate cartilage collagens in porcine osteochondrosis

1994 ◽  
Vol 107 (1) ◽  
pp. 47-59 ◽  
Author(s):  
R.J. Wardale ◽  
V.C. Duance
Keyword(s):  
Articular Cartilage ◽  
Growth Plate ◽  
Normal Tissue ◽  
Collagen Type ◽  
Hypertrophic Chondrocytes ◽  
Type I ◽  
Type X Collagen ◽  
Growth Plate Cartilage ◽  
Cartilage Lesions ◽  
Articular Cartilage Lesions

The articular and growth plate cartilages of osteochondrotic pigs were examined and compared with those from clinically normal animals. Both types of osteochondrotic cartilage showed considerable localised thickening apparently due to a lack of ossification. Histological examination of cartilage lesions demonstrated a breakdown in the normal pattern of chondrocyte maturation. Articular cartilage lesions lacked mature clones of chondrocytes in the calcifying region. Growth plate cartilage showed an accumulation of disorganised hypertrophic chondrocytes rather than the well-defined columns seen in normal tissue. The overall percentages of collagen in osteochondrotic lesions from both articular and growth plate cartilage were significantly reduced compared with levels in unaffected cartilage. There were substantial increases in the proportion of type I collagen in lesions from both osteochondrotic articular and growth plate cartilages and a reduction in the proportion of type II collagen. Type X collagen was detected in osteochondrotic but not normal articular cartilage. The proportion of type X collagen was unchanged in osteochondrotic growth plate cartilage. The levels of the collagen cross-links, hydroxylysylpyridinoline, hydroxylysyl-ketonorleucine and dehydrohydroxylysinonorleucine were radically reduced in samples from osteochondrotic growth-plate cartilage lesions when compared with normal tissue. Less dramatic changes were observed in articular cartilage although there was a significant decrease in the level of hydroxylysylketonorleucine in osteochondrotic lesions. Immunofluorescence examination of osteochondrotic lesions showed a considerable disruption of the organisation of the collagenous components within both articular and growth-plate cartilages. Normal patterns of staining of types I and VI collagen seen at the articular surface in unaffected tissue were replaced by a disorganised, uneven stain in osteochondrotic articular cartilage lesions. Incomplete removal of cartilage at the ossification front of osteochondrotic growth plate was demonstrated by immunofluorescence staining of type IX collagen. Type X collagen was produced in the matrix of the calcifying region of osteochondrotic articular cartilage by small groups of hypertrophic chondrocytes, but was not detected in normal articular cartilage. The distribution of type X collagen was unchanged in osteochondrotic growth plate cartilage.

The synthesis of type X collagen by bovine and human growth-plate chondrocytes

1991 ◽  
Vol 99 (3) ◽  
pp. 641-649 ◽  
Author(s):  
A. Marriott ◽  
S. Ayad ◽  
M.E. Grant
Keyword(s):  
Growth Plate ◽  
Type I Collagen ◽  
Polyacrylamide Gel Electrophoresis ◽  
Human Growth ◽  
Type I ◽  
Collagen Gels ◽  
Type X Collagen ◽  
Growth Plate Chondrocytes ◽  
Growth Plate Cartilage ◽  
Disulphide Bonds

Chondrocytes were isolated from bovine growth-plate cartilage and cultured within type I collagen gels. A major collagen with chains of Mr 59,000, decreasing to 47,000 on pepsinization, was synthesized and identified as type X collagen. This collagen was cleaved at two sites by mammalian collagenase, resulting in a major triple-helical fragment with chains of Mr 32,000. The species of Mr 59,000, 47,000 and 32,000 were not detected by SDS-polyacrylamide gel electrophoresis before reduction, indicating the presence of disulphide bonds within the triple helix. In contrast, similar biosynthetic studies with human growth-plate cartilage in organ culture, indicated that human type X collagen does not contain disulphide bonds. A polyclonal antiserum was raised to bovine type X collagen and used in immunolocalization studies to provide direct evidence for the association of type X collagen with the hypertrophic chondrocytes in both bovine and human growth plates during development.

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

2005 ◽  
Vol 25 (8) ◽  
pp. 3388-3399 ◽  
Author(s):  
Christopher B. Little ◽  
Clare T. Meeker ◽  
Rosalind M. Hembry ◽  
Natalie A. Sims ◽  
Kate E. Lawlor ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Growth Plate ◽  
Growth And Development ◽  
Type Ii Collagen ◽  
Skeletal Growth ◽  
Long Bone ◽  
Transitional Region ◽  
Type Ii ◽  
Hypertrophic Cartilage ◽  
Growth Plate Cartilage

ABSTRACT 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 N341 and F342 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.

Collagen expression in chicken tibial dyschondroplasia

1996 ◽  
Vol 109 (5) ◽  
pp. 1119-1131
Author(s):  
R.J. Wardale ◽  
V.C. Duance
Keyword(s):  
Growth Plate ◽  
Type I Collagen ◽  
Normal Growth ◽  
Type I ◽  
Type X Collagen ◽  
Growth Plate Chondrocytes ◽  
Growth Plate Cartilage ◽  
Tibial Dyschondroplasia ◽  
Collagen Expression

Collagen expression in growth plate cartilage derived from broiler chickens with tibial dyschondroplasia was studied and compared with samples from unaffected birds. Normal growth plate contains 12% collagen (dry weight) and dyschondroplastic growth plate 19% collagen compared with articular cartilage, which contains 55%. Dyschondroplastic growth plate collagens were more resistant to extraction by pepsin treatment than were those from unaffected growth plate. Normal and dyschondroplastic growth plate cartilages contain similar amounts of type I collagen (5% of the total collagen) but dyschondroplastic growth plate cartilage contains slightly less type II and type XI collagens, and significantly more type X collagen (25% as compared to 11%) than in normal growth plate. The levels of the mature collagen cross-link, hydroxylysyl-pyridinoline, are very low in normal growth plate but are six times higher in dyschondroplastic lesions. Immunolocalisation studies show that there is little change to the normal patterns of collagen organisation in dyschondroplastic growth plate. Investigation of metalloproteinase activity showed there to be a reduction in MMP-2 levels in dyschondroplastic growth plate compared to normal growth plate. In vitro studies on articular, normal growth plate and dyschondroplastic growth plate chondrocytes cultured in alginate or on plastic revealed differences between the cell types. When plated on plastic, articular chondrocytes rapidly assume a fibroblastic morphology. In contrast, normal growth plate chondrocytes retain their polygonal morphology whereas chondrocytes derived from dyschondroplastic cartilage initially exhibit both fibroblastic and polygonal phenotypes but gradually change to totally fibroblastic. These morphological changes are reflected by the collagen synthesis in vitro. Chondrocytes derived from normal articular cartilage synthesised collagen types I, II and X when cultured in alginate but type X synthesis was lost when cultured on plastic. Chondrocytes derived from normal growth plate cartilage synthesised predominantly type X collagen when cultured in either system. Chondrocytes derived from dyschondroplastic growth plate exhibited a similar phenotype to normal growth plate chondrocytes when cultured in alginate beads, but showed signs of dedifferentiation with reduced type X collagen and increased type I collagen when plated on plastic. These results suggest that the chondrocytes in dyschondroplastic growth plate cartilage are at a different stage of maturity than normal resulting in a cartilage that is failing to turn over at a normal rate.

CARTILAGE-SPECIFIC OVEREXPRESSION OF C-PROPEPTIDE OF TYPE II COLLAGEN AFFECTED MATRIX MINERALIZATION IN TRANSGENIC MICE

2003 ◽  
Vol 07 (03n04) ◽  
pp. 183-189
Author(s):  
Yoshito Matsui ◽  
Ken Nakata ◽  
Eijiro Adachi ◽  
Noriyuki Tsumaki ◽  
Tomoatsu Kimura ◽  
...  
Keyword(s):  
Bone Formation ◽  
Transgenic Mice ◽  
Growth Plate ◽  
Type Ii Collagen ◽  
Whole Body ◽  
Endochondral Bone Formation ◽  
Type Ii ◽  
Endochondral Bone ◽  
Matrix Mineralization ◽  
Growth Plate Cartilage

The C-propeptide of type II collagen (CppII) is cleaved from the procollagen molecule at the time of extracellular secretion from chondrocytes, and was reported to localize in the lower hypertrophic zone of the growth plate cartilage. In the present study, the in vivo role of CppII in the process of endochondral bone formation was investigated by cartilage-specific overexpression of CppII in transgenic mice. Two independent lines of transgenic mice were obtained and they showed mild skeletal dysplasia, as evidenced by morphometric measurement of skeletal bones. Whole body staining revealed delayed mineralization of embryonic endochondral bones, including occipital bone and vertebral bodies. Histological sections showed reduced area of mineralization and scattered chondrocyte hypertrophy in the lower part of growth plate cartilage in the embryonic long bones. Immuno-electron micrographs demonstrated that CppII co-localized with collagen fibrils in the extracellular matrix of the cartilage. Taken together, these results indicate that overexpression of CppII affected endochondral bone formation by negatively regulating the matrix mineralization.

Quantification and immunolocalisation of porcine articular and growth plate cartilage collagens

1993 ◽  
Vol 105 (4) ◽  
pp. 975-984 ◽  
Author(s):  
R.J. Wardale ◽  
V.C. Duance
Keyword(s):  
Articular Cartilage ◽  
Growth Plate ◽  
Type I Collagen ◽  
Articular Surface ◽  
Dry Weight ◽  
Type I ◽  
Collagen Types ◽  
Growth Plate Cartilage ◽  
The Matrix ◽  
Cross Links

The collagens of growth plate and articular cartilage from 5–6 month old commercial pigs were characterised. Growth plate cartilage was found to contain less total collagen than articular cartilage as a proportion of the dry weight. Collagen types I, II, VI, IX and XI are present in both growth plate and articular cartilage whereas type X is found exclusively in growth plate cartilage. Types III and V collagen could not be detected in either cartilage. Type I collagen makes up at least 10% of the collagenous component of both cartilages. There are significant differences in the ratios of the quantifiable collagen types between growth plate and articular cartilage. Collagen types I, II, and XI were less readily extracted from growth plate than from articular cartilage following pepsin treatment, although growth plate cartilage contains less of the mature collagen cross-links, hydroxylysyl-pyridinoline and lysyl-pyridinoline. Both cartilages contain significant amounts of the divalent reducible collagen cross-links, hydroxylysyl-ketonorleucine and dehydro-hydroxylysinonorleucine. Immunofluorescent localisation indicated that type I collagen is located predominantly at the surface of articular cartilage but is distributed throughout the matrix in growth plate. Types II and XI are located in the matrix of both cartilages whereas type IX is predominantly pericellular in the calcifying region of articular cartilage and the hypertrophic region of the growth plate. Collagen type VI is located primarily as a diffuse area at the articular surface.

Localization of type X collagen in canine growth plate and adult canine articular cartilage

1991 ◽  
Vol 9 (4) ◽  
pp. 485-494 ◽  
Author(s):  
James M. Gannon ◽  
Gordon Walker ◽  
Mark Fischer ◽  
Randy Carpenter ◽  
Roby C. Thompson ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Growth Plate ◽  
Type X Collagen

Properties of Cartilage–Subchondral Bone Junctions: A Narrative Review with Specific Focus on the Growth Plate

Cartilage ◽  
2020 ◽  
pp. 194760352092477
Author(s):  
Masumeh Kazemi ◽  
John Leicester Williams
Keyword(s):  
Mechanical Properties ◽  
Articular Cartilage ◽  
Growth Plate ◽  
Subchondral Bone ◽  
Bone Growth ◽  
Narrative Review ◽  
Bimaterial Interface ◽  
Bone Interface ◽  
Growth Plate Cartilage ◽  
Specific Focus

Objective The purpose of this narrative review is to summarize what is currently known about the structural, chemical, and mechanical properties of cartilage-bone interfaces, which provide tissue integrity across a bimaterial interface of 2 very different structural materials. Maintaining these mechanical interfaces is a key factor for normal bone growth and articular cartilage function and maintenance. Materials and Methods A comprehensive search was conducted using Google Scholar and PubMed/Medline with a specific focus on the growth plate cartilage–subchondral bone interface. All original articles, reviews in journals, and book chapters were considered. Following a review of the overall structural and functional characteristics of the physis, the literature on histological studies of both articular and growth plate chondro-osseous junctions is briefly reviewed. Next the literature on biochemical properties of these interfaces is reviewed, specifically the literature on elemental analyses across the cartilage–subchondral bone junctions. The literature on biomechanical studies of these junctions at the articular and physeal interfaces is also reviewed and compared. Results Unlike the interface between articular cartilage and bone, growth plate cartilage has 2 chondro-osseous junctions. The reserve zone of the mature growth plate is intimately connected to a plate of subchondral bone on the epiphyseal side. This interface resembles that between the subchondral bone and articular cartilage, although much less is known about its makeup and formation. Conclusion There is a notably paucity of information available on the structural and mechanical properties of reserve zone–subchondral epiphyseal bone interface. This review reveals that further studies are needed on the microstructural and mechanical properties of chondro-osseous junction with the reserve zone.

Enhanced Early Tissue Regeneration after Matrix-Assisted Autologous Mesenchymal Stem Cell Transplantation in Full Thickness Chondral Defects in a Minipig Model

2009 ◽  
Vol 18 (8) ◽  
pp. 923-932 ◽  
Author(s):  
Martin Jung ◽  
Balazs Kaszap ◽  
Anna Redöhl ◽  
Eric Steck ◽  
Steffen Breusch ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Collagen Type ◽  
Type I ◽  
Type Ii ◽  
Collagen Type Ii ◽  
Histomorphometric Analysis ◽  
Tissue Quality ◽  
Repair Tissue ◽  
Adult Mesenchymal Stem Cells ◽  
Defect Area

Adult mesenchymal stem cells (MSCs) are an attractive cell source for new treatment strategies in regenerative medicine. This study investigated the potential effect of matrix assisted MSC transplantation for articular cartilage regeneration in a large-animal model 8 weeks postoperatively. MSCs from bone marrow aspirates of eight Goettingen minipigs were isolated and expanded prior to surgery. Articular cartilage defects of 5.4 mm were created bilaterally in the medial patellar groove without penetrating the subchondral bone plate. Defects were either left empty ( n = 4), covered with a collagen type I/III membrane ( n = 6) or additionally treated with autologous MSC transplantation (2 × 106; n = 6). After 8 weeks animals were euthanized and the defect area was assessed for its gross appearance. Histomorphological analysis of the repair tissue included semiquantitative scoring (O'Driscoll score) and quantitative histomorphometric analysis for its glycosaminoglycan (GAG) and collagen type II content. All membranes were found to cover the defect area 8 weeks postoperatively. Median defect filling was 115.8% (membrane), 117.8% (empty), and 100.4% (MSC), respectively (not significant). Histomorphological scoring revealed significantly higher values in MSC-treated defects (median 16.5) when compared to membrane treatment (median 9.5) or empty defects (median 11.5; p = 0.015 and p = 0.038). Histomorphometric analysis showed larger GAG/collagen type II-positive areas in the MSC-treated group (median 24.6%/29.5% of regeneration tissue) compared to 13.6%/33.1% (empty defects) and 1.7%/6.2% (membrane group; p = 0.066). Cell distribution was more homogeneous in MSC compared to membrane-only group, where cells were found mainly near the subchondral zone. In conclusion, autologous matrix-assisted MSC transplantation significantly increased the histomorphological repair tissue quality during early articular cartilage defect repair and resulted in higher GAG/collagen type II-positive cross-sectional areas of the regenerated tissue.

Sign in / Sign up

Export Citation Format

Share Document