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PubMed2006

Age-related differences in articular cartilage wound healing: a potential role for transforming growth factor beta1 in adult cartilage repair.

Objective of this study was to investigate the early wound healing reactions of immature and mature articular cartilage on experimental wound healing in the New Zealand White rabbit. The proliferation potential and glycosaminoglycan production of isolated chondrocytes of these animals was studied in an alginate culture system. A band of tissue with death chondrocytes was observed at wound edges of immature articular cartilage, whereas mature cartilage showed a significant smaller amount of dead chondrocytes. A general increase in TGFbeta1, FGF2 and IGF1 was observed throughout cartilage tissue with the exception of lesion edges. The observed immunonegative area appeared to correlate with the observed cell death in lesion edges. Repair in immature cartilage was indicated by chondrocyte proliferation in clusters and a decrease in defect size. No repair response was observed in mature articular cartilage defects. The alginate culture experiment demonstrated a higher proliferation rate of immature chondrocytes. Addition of recombinant TGFbeta1 increased proliferation rate and GAG production of mature chondrocytes. We were not able to further stimulate immature chondrocytes. These results indicate that TGFbeta1 addition may contribute to induce cartilage repair responses in mature cartilage as observed in immature, developing cartilage.

Aging↗
PubMed2005

Changing the convexity and concavity of nasal cartilages and cartilage grafts with horizontal mattress sutures: part II. Clinical results.

Horizontal mattress sutures have previously been shown to remove unwanted bulbosity and convexity of nasal tip cartilages. The purpose of this study was to extend that concept by investigating the universal applicability of the horizontal mattress suture to change and control the curvature (e.g., convexity or concavity) of a wide variety of nasal cartilages and warped cartilage grafts. The horizontal mattress suture was applied to a variety of clinical situations, including nasal tip bulbosity caused by convex lateral crura, collapsed external nasal valves, warped grafts and struts, crooked L-shaped septal struts, and collapsed internal nasal valves. Twenty-nine cases were studied over a period of 10 to 23 months. The horizontal mattress suture proved to be a simple, effective means of achieving satisfactory control of the curvature of various cartilages of the nose (including external valves, internal valves, and septum) and warped cartilage grafts. Curvature control was obtained in all cases where the cartilage was supple. Moreover, the resultant strength was increased above normal. Partial recurrence of the curvature was seen in only two cases. Clinical results indicated that the horizontal mattress suture is universally applicable to a variety of situations in which the curvature of nasal cartilage and cartilage grafts needs to be removed or modified. The mattress suture drastically reduces the need for scoring (with its inherent problems of weakness) and the need for cartilage grafting.

Cartilage↗
PubMed1978

Vitamin D and cartilage. I. In vitro metabolism of 25-hydroxycholecalciferol by cartilage.

In the present work, the capacity of cartilage to metabolize 25-hydroxycholecalciferol was investigated. Cartilage preparations from growth plate, articular surface, rib, scapula, and ear were isolated from 3-week-old normal rabbits and chickens. Each tissue was separately incubated with tritiated 25-hydroxycholecalciferol (, x 10(-9) M) for 1-24 h. Incubations of kidney and muscle were performed simultaneously for comparison. Similarly, cultured chondrocytes isolated from rabbit growth plate and articular cartilage were incubated for 1 or 20 h in medium free of fetal calf serum. After methanol-chloroform extraction of tissues, cells, and their respective media, chloroform phases were chromatographed on Sephadex LH-20 columns. The results show that kidney and cartilage are able to convert 25-hydroxycholecalciferol into a derivative which migrates in the 24,25-dihydroxycholecalciferol region. Cartilage tissue previously boiled is unable to metabolize 25-hydroxycholecalciferol. The conversion of 25-hydroxycholecalciferol occurs with all types of cartilage and is also observed in incubations of cultured chondrocytes. In the latter, the polar 25-hydroxycholecalciferol derivative is detected as early as 1 h after addition of 25-hydroxycholecalciferol. Two findings suggest that the polar derivative of 25-hydroxycholecalciferol produced by cartilage is 24,25-dihydroxycholecalciferol: 1) the cartilage derivative and 24,25-dihydroxycholecalciferol (synthetic and biosynthetic) comigrate during Sephadex LH-20 and high liquid pressure chromatography; and 2) both the cartilage derivative and 24,25-dihydroxycholecalciferol are sensitive to periodate treatment.

Animals↗
PubMed2004

[Value of osteo-chondral paste autologous transplantation in experimental cartilage defects reconstruction. Part III--Microscopic analysis of reconstructed cartilage thickness and surface regularity].

INTRODUCTION: A limited ability of the cartilage to heal after trauma was the reason to start research on new methods concerning better cartilage reconstruction. The aim of the study was evaluation of repair tissue thickness and surface regularity after osteochondral paste transplantation. MATERIAL AND METHODS: Full thickness defect (IV(o)--ICRS scale) on distal rabbit femur joint surface was made. Three groups were specified: A--defect with paste graft (cartilage and contiguous bone collected from joint surface, crushed into homogenous paste; B--defect with the paste graft covered with periosteum; C--defect left unfilled. The follow-up periods were established at 4, 8, 12 weeks. Repair tissue was evaluated microscopically according to modified O'Driscoll scale. RESULTS: Newly formed tissue was well integrated with surrounding cartilage in group A (paste graft). That trait of repair tissue in group A was much better than in other groups, especially in late observations. Structural integrity of tissue filling the defect was similar to integrity of normal cartilage in groups A and C, but tissue formed in group C didn't represent a hyaline-like cartilage character. In all the examined groups reconstruction of subchondral bone exhibited similar rate. 12 weeks from the procedure, around 80% of subchondral bone was rebuilt. The obtained results indicate, that osteochondral paste autologous transplantation in cartilage defects treatment effects with forming well integrated (structurally and with surrounding cartilage) cartilage tissue, of almost complete subchondral bone rebuilding.

Animals↗
PubMed1984

[Cellular aspects of the aging of the articular cartilage. II. Condylar cartilage with fissured surface taken from normal and arthritic knees].

The authors studied the cellular density (number of cells per mm2) of cartilage taken from the femoral condyles of 46 cadavers (73 knees). In each case, the cartilage was taken from the summit of the condyle and, in 46 joints (27 subjects), a sample was also taken from the posterior surface (non weight-bearing zones). The fragments of non-calcified cartilage were sectioned with a cryostat and the sections (10 micrometers) were stained with hematein-eosin and solid red-Alcian blue. This study demonstrates: 1) a decrease in the cellular density of fissured cartilage compared to normal cartilage; this decrease appears to be proportional to the degree of fibrillation; 2) a decrease in the cellular density of apparently normal cartilage from arthrotic joints compared with normal cartilage from healthy joints; 3) with the age of the subjects, an increase in the density of the clones (number of clones per mm2) and the density of clonal cells (number of clonal cells per mm2) together with a decrease in the mean number of chondrocytes per clone. In fissured cartilage, the density of the clones, the density of the clonal cells and the number of chondrocytes per clone are slightly higher on the posterior surface of the condyles than on the summit of the condyles. These results emphasise the importance of the role that might be played by cellular phenomena in the mechanisms of deterioration of cartilage with aging and with arthrosis.

Adult↗
PubMed1998

Presence of cartilage-derived morphogenetic proteins in articular cartilage and enhancement of matrix replacement in vitro.

OBJECTIVE: To investigate the effects of the cartilage-derived morphogenetic proteins (CDMPs) in an in vitro cartilage explant model that mimics the chondrocytic response to matrix depletion, and to demonstrate their presence in articular cartilage. METHODS: Adult bovine articular cartilage and postmortem specimens from adult human donors with and without osteoarthritic (OA) lesions were stained by immunohistochemistry using polyclonal antibodies specific for CDMP-1 and CDMP-2. Extracts of bovine articular cartilage were analyzed by Western blotting for the presence of the CDMPs. Bovine articular cartilage explants were depleted of their matrix by trypsin digestion, followed by a 7-day culture period in a chemically defined serum-free basal medium (BM), with or without recombinant CDMPs 1 and 2. The metabolic activity of chondrocytes was measured by 35S-sulfate incorporation into macromolecules. Newly synthesized proteoglycans (PGs) were analyzed using Sephacryl S-500 HR gel chromatography. The expression levels of the messenger RNA (mRNA) for chondrogenic markers were investigated by Northern analysis. RESULTS: CDMP-1 and CDMP-2 were detected in both bovine and human healthy and OA articular cartilage. Treatment of matrix-depleted cartilage explants with CDMPs 1 and 2 increased equally the incorporation of 35S-sulfate into PGs compared with tissue maintained in BM. Gel chromatography analysis indicated that aggrecan was the predominant PG species. Northern blot analysis showed that the expression of link protein, type II collagen, and aggrecan mRNA transcripts was not modulated by CDMP treatment. CONCLUSION: This study shows the presence of CDMP-1 and CDMP-2 in adult bovine and human articular cartilage. In addition, our in vitro data indicate that CDMPs 1 and 2 stimulate the metabolic activity of articular chondrocytes. Therefore, these signaling molecules may be contributing to the maintenance of the integrity of the joint surface.

Animals↗
PubMed2000

Effects of harvest and selected cartilage repair procedures on the physical and biochemical properties of articular cartilage in the canine knee.

This study utilizes a canine model to quantify changes in articular cartilage 15-18 weeks after a knee joint is subjected to surgical treatment of isolated chondral defects. Clinical and experimental treatment of articular cartilage defects may include implantation of matrix materials or cells, or both. Three cartilage repair methods were evaluated: microfracture, microfracture and implantation of a type-II collagen matrix, and implantation of an autologous chondrocyte-seeded collagen matrix. The properties of articular cartilage in other knee joints subjected to harvest of articular cartilage from the trochlear ridge (to obtain cells for the cell-seeded procedure) were also evaluated. Physical properties (thickness, equilibrium compressive modulus, dynamic compressive stiffness, and streaming potential) and biochemical composition (hydration, glycosaminoglycan content, and DNA content) of the cartilage from sites distant to the surgical treatment were compared with values measured for site-matched controls in untreated knee joints. No significant differences were seen in joints subjected to any of the three cartilage repair procedures. However, a number of changes were induced by the harvest operation. The largest changes (displaying up to 3-fold increases) were seen in dynamic stiffness and streaming potential of patellar groove cartilage from joints subjected to the harvest procedure. Whether the changes reported will lead to osteoarthritic degeneration is unknown, but this study provides evidence that the harvest procedure associated with autologous cell transplantation for treatment of chondral defects may result in changes in the articular cartilage in the joint.

Animals↗
PubMed1999

Immunohistochemical localization of fibroblast growth factor receptors in the rat mandibular condylar cartilage and tibial cartilage.

The fibroblast growth factor receptors (FGFRs), members of the tyrosine-kinase receptor family, are known to play a crucial role in the growth and development of cartilaginous tissues. The mandibular condylar cartilage has been suggested to have a characteristic growth pattern compared with the tibial growth plate cartilage, e.g., cell alignment, mode of proliferation and differentiation, and response to humoral and mechanical factors. To examine the mRNA expression and localization of fibroblast growth factor receptor (FGFR)-1, -2, and -3 in the condylar and tibial growth plate cartilages, reversed transcribed polymerase chain reaction (RT-PCR) assay and immunohistochemistry were carried out using growing rats. The enzymatically isolated rat condylar and tibial chondrocytes expressed mRNA of aggrecan and type II collagen, which are together known as the major cartilaginous extracellular matrices. Both types of cells expressed mRNA of FGFR-1, -2, and -3 by RT-PCR. In the neonatal rat, immunolocalization of FGFR-1, -2, and -3 was found in the middle of the condylar cartilage, mainly in the hypertrophic zone of the tibial cartilage. At 3 weeks old, the three FGFRs were broadly observed in both cartilages. At 8 weeks old, localization of FGFR-3 was absent in the hypertrophic cell layer of the condyle, whereas it was still broadly observed in the tibial growth plate cartilage. In the same stage, FGFR-1 and FGFR-2 showed similar localization in both cartilages to that at 3 weeks of age. All these observations suggest that FGFRs play an important role in the differential growth pattern of the condylar cartilage.

Animals↗
PubMed1995

Cartilage morphogenesis: role of bone and cartilage morphogenetic proteins, homeobox genes and extracellular matrix.

Cartilage morphogenesis is one of the central topics in skeletal development. Cartilage geometry determines the future architecture of bones, joints and associated ligaments and tendons. Recent progress in this area has come from purification, cloning and expression of genes encoding bone and cartilage morphogenetic proteins (BMPs and CDMPs). BMPs initiate de novo cartilage and bone differentiation. BMPs are a family of pleiotropic signals for progenitor cell migration by chemotaxis, proliferation, and differentiation. Very recently another class of related morphogenetic proteins, CDMPs have been isolated and cloned. CDMPs may be critical for mesenchymal condensation prior to overt cartilage differentiation, the first step in morphogenesis of both cartilage and bone. The cartilage morphogenetic cascade is a cellular and molecular continuum driven by regulatory signalling molecules such as BMPs and CDMPs and their receptors, homeobox genes, transcription factors, and finally the synthesis and supramolecular assembly of structural macromolecules of the extracellular matrix. BMPs and CDMPs bind to heparin, heparan sulfates, and collagens I and IV. Thus there is a symbiosis of regulatory and structural macromolecules in the morphogenesis of cartilage. An avalanche of recent advances from seemingly disparate areas bodes well for the complete elucidation of the molecular basis of morphogenesis of cartilage, the architectural blue-print for the skeleton.

Animals↗
PubMed2001

Growth factor expression in cartilage wound healing: temporal and spatial immunolocalization in a rabbit auricular cartilage wound model.

OBJECTIVE: The ability of cartilage to regenerate following injury is limited, potentially leading to osteoarthritis. Integrative cartilage repair, necessary for durable restoration of cartilage lesions, can be regarded as a wound healing process. Little is known about the effects of growth factors regulating acute cartilage wound healing in vivo. In this study the temporal expression patterns of growth factors and proteoglycan content in cartilage wound edges in vivo were studied. DESIGN: Cartilage wounds were created in rabbit ear cartilage using a 6 mm biopsy punch. Specimens were subsequently harvested 1, 3, 7, 14 and 28 days after surgery. Paraffin sections were thionin stained to visualize proteoglycan loss and replacement. Immunohistochemical staining of TGFbeta1, TGFbeta3, IGF-1, IGF-II and FGF-2 was used to define growth factor expression at the cartilage wound sites. RESULTS: Almost no effect of cartilage wounding was observed one day after surgery. A decrease of proteoglycan content, with a maximal loss at day 7, and a subsequent restoration was observed at the wound edges. Growth factor expression increased simultaneously. Maximal immunostaining for IGF1, IGFII, FGF2 and TGF-beta3 was observed at day 7, followed by a gradual decrease. Increased expression of TGFbeta1 lasted from day 3 until day 14. CONCLUSION: We have demonstrated the ability of chondrocytes to increase growth factor expression and to restore the rapid decrease in proteoglycan content in the initial phase following acute wounding. A temporal increase in intracellular growth factor expression suggests an autocrine and/or paracrine metabolic stimulation, which can be regarded a sign of chondrocytes repair capacity.

Animals↗
PubMed2006

Tissue engineered cartilage integration to live and devitalized cartilage: a study by reflectance mode confocal microscopy and standard histology.

This study investigated the in vivo formation of engineering cartilage within living or devitalized cartilage discs using reflectance mode confocal microscopy and conventional light microscopy. Pig articular chondrocytes were suspended in fibrin glue and placed between two cartilage discs. Four experimental groups were prepared: in groups 1 and 2, the cell-hydrogel composite was placed between two live or between two devitalized cartilage discs, respectively; in groups 3 and 4, acellular fibrin glue was placed between two live or between two devitalized cartilage discs, respectively. Samples were implanted in the back of nude mice and analyzed after 2, 5, and 8 weeks. Results showed that engineered cartilage seems to grow more homogenously when the cell-seeded gel was placed between devitalized cartilages than when it was placed between live cartilage matrices. Confocal microscopy provides valuable information on the integration of tissue-engineered cartilage with native tissue and could be useful for nondestructive imaging in vivo.

Animals↗
PubMed2001

The relationship of the compressive modulus of articular cartilage with its deformation response to cyclic loading: does cartilage optimize its modulus so as to minimize the strains arising in it due to the prevalent loading regime?

AIM: To investigate the relationship of the instantaneous compressive modulus with its deformation response to cyclic loading typical of that encountered at the knee joint during level walking. METHOD: The study was performed on 24 osteochondral plugs taken from three unembalmed cadaveric knees. As the compressive modulus of cartilage has been shown to vary topographically across the knee in an established manner, the specimens were taken from specific sites on the femur and tibia of each knee. All the cartilage specimens were immersed in Hanks' salt solution at 37 degrees C and were subjected to the same cyclic loading regimen that was representative of a typical walking cycle in a specialized indentation apparatus, for over 1 h. RESULTS AND CONCLUSION: The viscous and elastic components of matrix strain, the creep rate and the cartilage compressive modulus were measured. The latter was found to be significantly related to the strain response of cartilage to cyclic loading. Elastic strain varied exponentially with the compressive modulus; specimens with a modulus less than 4 MPa experienced elastic strains in the range 0.18-0.36, whereas stiffer specimens experienced strains between 0.05 and 0.13. Viscous strain varied linearly with cartilage stiffness and was as low as 0.02 at the lower values of the compressive modulus but increased to 0.22 for a compressive modulus of 18 MN/m(2). The rate of creep under cyclic load was inversely linearly related to cartilage stiffness. The strain response of soft specimens approached steady state by 200 cycles but that of stiff specimens did not approach it until 1300 cycles. It was hypothesized that the viscous strain response of cartilage can be explained in terms of differences in permeability between specimens of different compressive modulus, stiffer cartilage having a lower permeability than soft cartilage.

Cadaver↗
PubMed1991

Cartilage canals and lesions typical of osteochondrosis in growth cartilages from the distal part of the humerus of newborn pigs.

Vessels in cartilage canals supplying the articular-epiphyseal cartilage complex and growth plate of the distal part of the humerus of pigs between on day and 15 weeks old were examined in perfused and cleared specimens, and histochemical preparations. An extensive capillary network surrounded the arterioles and venules and probably maintained the circulation of blood as the ends of the cartilage canals underwent involution. Pits and grooves were in predilection sites for osteochondrosis and osteoarthrosis and were typical of early lesions of these conditions. Some ghosts that were observed mesoscopically were chondrified cartilage canals or remnants of cartilage canals in histological sections, and were considered to be the result of a normal process. However, abnormal involution may predispose to chrondrolysis, and the presence of involuting transverse cartilage canals at predilection sites implicated damaged canals in the aetiopathogenesis of osteochondrosis and osteroarthrosis in some pigs. Cleared specimens provided the most useful demonstration of the form and distribution of cartilage canals, ghosts, and pits or grooves. The association of cartilage canals with areas of chondrolysis, and the distribution of ghosts in the predilection sites for lesions, warrant further investigation of blood vessels within cartilage canals.

Animals↗
PubMed1993

Expression of 92-kD type IV collagenase/gelatinase (gelatinase B) in osteoarthritic cartilage and its induction in normal human articular cartilage by interleukin 1.

We report here that a 92-kD gelatinolytic metalloproteinase is expressed as protein and mRNA in human osteoarthritic cartilage, but not in normal adult articular cartilage. Western immunoblotting demonstrated that the 92-kD gelatinolytic activity corresponded to 92-kD type IV collagenase/gelatinase (gelatinase B); mRNA for gelatinase B was identified by Northern blotting. Chondrocytes from normal cartilage also exhibited mRNA for 72-kD type IV collagenase/gelatinase (gelatinase A), tissue collagenase, and stromelysin-1, and these mRNAs were increased in osteoarthritic cartilage. Regional analysis of osteoarthritic cartilage samples from four individuals revealed that gelatinase B mRNA was expressed in grossly fibrillated areas; two of four nonfibrillated cartilage samples failed to exhibit the mRNA, but did have increased levels of mRNA for other neutral metalloproteinases. IL-1 alpha treatment of normal human cartilage explants or isolated chondrocytes induced increased levels of gelatinase B and increased mRNA for tissue collagenase and stromelysin-1. Under identical conditions, mRNA levels for gelatinase A were not increased indicating that regulation of this enzyme in human articular chondrocytes is distinct from that of other metalloproteinases. Our data showing expression of gelatinase B in fibrillated cartilage suggest that it is a marker of progressive articular cartilage degradation in osteoarthritis.

Adult↗
PubMedDate not supplied

Temperature requirements for altering the morphology of osteoarthritic and nonarthritic articular cartilage: in vitro thermal alteration of articular cartilage.

BACKGROUND: Radiofrequency and laser thermal chondroplasty procedures are performed to debride and smooth fibrillated, articular cartilage. HYPOTHESIS: Temperature requirements necessary to achieve morphological change will be lower in fibrillated arthritic cartilage as compared with nonarthritic articular cartilage. STUDY DESIGN: Controlled laboratory study. METHODS: A thermal cell-culture chamber was mounted on a stereoscopic microscope and coordinated with a custom temperature-control program. Nonarthritic and osteoarthritic articular cartilage specimens were sectioned into full-thickness slices. The articular sections were exposed to temperatures incrementally from 37 masculine C to 75 masculine C. Real-time, digital capture microscopy was used to visualize and analyze the morphological changes undergone by the articular cartilage specimens. RESULTS: Arthritic articular cartilage displayed morphological change at 56.5 +/- 1.7 masculine C. Loss of fibrillation was the initial morphological change visualized. Continued thermal exposure caused a shrinkage effect of the entire tissue section that was similar to the change seen in nonarthritic sections. Nonarthritic cartilage displayed morphological change at 60.9 +/- 1.9 masculine C. CONCLUSIONS: Consistent characteristic morphological changes were found at distinct temperatures in osteoarthritic and nonarthritic articular cartilage. CLINICAL RELEVANCE: This information begins to establish the thermal parameters required for morphological change of osteoarthritic articular cartilage.

Cartilage, Articular↗
PubMed1997

A new biological glue for cartilage-cartilage interfaces: tissue transglutaminase.

In this study, we used an in vitro model to test the capacity of tissue transglutaminase to increase the adhesive strength at a cartilage-cartilage interface. Full-thickness cartilage-bone cylinders were prepared from fresh adult bovine shoulder joints, and the superficial half of the hyaline cartilage was then removed to provide a plane surface. Tissue transglutaminase was applied to the freshly cut surface of one cylinder, and a calcium-chloride solution (to act as an activating agent) was applied to that of the other. The cartilage surfaces were immediately apposed, one on top of the other, and an eighty-gram weight was applied to the upper cylinder for ten minutes at 37 degrees Celsius under defined humidity conditions. A measured force was then applied transversely to the upper cylinder until it was displaced from the lower one (which was clamped in a holding device), and the force recorded at this point was taken as a measure of the adhesive strength achieved at the cartilage-cartilage interface. The adhesive strength increased linearly with an increasing concentration of tissue transglutaminase (0.25 to 2.75 milligrams per milliliter) and was enhanced by increasing the duration of incubation, but it was not influenced by the level of humidity. The adhesive strength was improved by as much as 40 per cent when the cartilage surfaces had been pretreated with chondroitinase AC or hyaluronidase to remove glycosaminoglycan chains of proteoglycans, which are largely responsible for the intrinsic anti-adhesive properties of cartilage.

Adhesiveness↗
PubMed2005

Increased type II collagen degradation and very early focal cartilage degeneration is associated with upregulation of chondrocyte differentiation related genes in early human articular cartilage lesions.

OBJECTIVE: Articular cartilage degeneration in osteoarthritis (OA) involves excessive degradation of extracellular matrix (ECM) and chondrocyte differentiation (hypertrophy). We determined the interrelationship between the extent of collagen cleavage by collagenase, cartilage degeneration, and differentiation related gene expression in patella-femoral condylar cartilages of patients bearing very early focal OA-like articular cartilage lesions. METHODS: Articular cartilage specimens with very early focal lesions and adjacent normal cartilage from 3 donors were removed at autopsy as full-depth slices cut from the femoral condyle surface that articulates with patella. Slices were divided into sections and used for Mankin grading, examination of collagenase cleavage of type II collagen by ELISA, and gene expression by RT-PCR. RESULTS: Early focal cartilage degeneration was associated with increased collagenase cleavage of type II collagen. The collagenases metalloproteinase-1 (MMP-1), MMP-14 (MT1-MMP), and aggrecanase ADAMTS-5 (a disintegrin and metalloprotease with thrombospondin motifs) (but not ADAMTS-4); cytokines interleukin 1alpha/beta and tumor necrosis factor-alpha (TNF-alpha); chondrocyte terminal differentiation-related genes COL10A1, MMP-13, MMP-9, Indian hedgehog; and caspase 3 were often upregulated in the vicinity of the lesion. Growth factors associated with growth plate chondrocyte proliferation, namely fibroblast growth factor-2, parathyroid hormone related protein, transforming growth factor (TGF)-beta1/2, as well as the matrix molecules COL2A1 and aggrecan were expressed adjacent to and remote from the lesion. Of all genes only caspase 3 and ADAMTS-5 expression was exclusively seen in association with these early lesions. Elevation of collagenase activity was associated with a frequent elevation of expression of COL10A1, caspase 3, IL-1alpha/beta, MMP-1, and ADAMTS-5, and a decreased expression of Sox-9 (SRY-type high-mobility-group box transcription factor-9), TGF-beta1, TGF-beta2, TNF-alpha, and aggrecan. Other genes showed no observable difference with changes in collagenase activity. CONCLUSION: Very early focal degeneration in knee articular cartilage is accompanied by upregulation of collagenase activity and expression of genes associated with chondrocyte terminal differentiation and matrix degradation. Thus chondrocyte differentiation may be closely related to the very early development of cartilage degeneration such as occurs in OA.

Aged↗
PubMed2006

An in situ hybridization and histochemical study of development and postnatal changes of mouse mandibular angular cartilage compared with condylar cartilage.

To investigate the origin and postnatal changes of mouse mandibular angular cartilage, in situ hybridization for cartilaginous marker proteins, histochemistry for alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP), and bromodeoxyuridine (BrDU) analyses were performed. Chondrocytes of the mandibular angular cartilage were derived from ALP-positive progenitor cells and first detected at embryonic day (E) 15.5. Newly formed chondrocytes rapidly differentiated into hypertrophic chondrocytes and hypertrophic cell zone rapidly extended in subsequent a few days. During this period, bone sialoprotein mRNA was more widely expressed than osteopontin mRNA in cartilage. Endochondral bone formation started at E 17.5 with the resorption of the bone collar by osteoclasts. These characteristics were consistent with those of the condylar cartilage, although developmental process was 0.5-1.5 day delayed relative to the condylar cartilage. During the postnatal period, contrast to the condylar cartilage, the angular cartilage constantly decreased in volume with advancing age. Reduction of proliferating activity estimated by BrDU incorporation accounts for this phenomenon. We demonstrate new structural features of the mandibular angular cartilage that may contribute to a coming research for the secondary cartilage.

Aggrecans↗