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PubMed1999

The role of trabecular demineralized bone in combination with perichondrium in the generation of cartilage grafts.

The use of a composite graft of bovine trabecular demineralized bone matrix (DBM) and perichondrium has been found a reliable method for in vivo generation of cartilage. In the present study, the mechanism whereby this commercially available matrix increases cartilage formation was investigated. First, the time course of cartilage formation in vivo, in the combined implant of perichondrium and DBM in the rabbit ear was studied, with special focus on tissue reactions to DBM. DBM was colonized by macrophages from day 3 post-operatively, reaching a maximum after 2 weeks. Only a minimal number of neutrophils was found. After 3 weeks the DBM appeared to be resorbed. In the first week the DBM was invaded with chondroblasts, and chondrogenesis occurred between the first and second week of implantation. After 3 weeks, the initially formed islets of cartilage had fused. Next, the chondrogenic capacity of DBM itself was investigated by implantation of DBM without perichondrium. This never resulted in cartilage formation. Immunohistochemistry showed only a faint staining of the DBM for growth factors. This indicates a minimal chondrogenic effect of DBM alone and the requirement of perichondrium as cell provider. In order to define the conditions which cause chondrogenesis in composites of perichondrium and DBM, a series of in vitro culture experiments was performed in which the in vivo situation was mimicked step by step. The basic condition was perichondrium cultured in medium with 10% FCS. In this condition, cartilage formation was variable. Because in the in vivo situation both DBM and macrophages can release growth factors, the effect of IGF1, TGFbeta2 or OP1 added to the culture medium was tested. Neither the incidence nor the amount of cartilage formation was stimulated by addition of growth factors. Perichondrium wrapped around DBM in vitro gave cartilage formation in the perichondrium but the incidence and amount were not significantly stimulated compared to cultures of perichondrium without DBM. However, cartilage-like cells were found in the DBM suggesting an effect of DBM on perichondrium-derived cells. Finally, macrophages and/or blood were added to the composite DBM-perichondrium to mimic the in vivo situation as close as possible. However, no effect of this treatment was found. In conclusion, this study indicates that DBM itself has few chondrogenic qualities but functions merely as a spacer for cell ingrowth. The fast resorption of DBM by macrophages in vivo seems of importance for the cartilage forming process, but in vitro the presence of macrophages (in combination with blood) could not enhance chondrogenesis.

Animals↗
PubMed2000

Pretreatment with platelet derived growth factor-BB modulates the ability of costochondral resting zone chondrocytes incorporated into PLA/PGA scaffolds to form new cartilage in vivo.

Optimal repair of chondral defects is likely to require both a suitable population of chondrogenic cells and a biodegradable matrix to provide a space-filling structural support during the early stages of cartilage formation. This study examined the ability of chondrocytes to support cartilage formation when incorporated into biodegradable scaffolds constructed from copolymers (PLG) of polylactic acid (PLA) and polyglycolic acid (PGA) and implanted in the calf muscle of nude mice. Scaffolds were fabricated to be more hydrophilic (PLG-H) or were reinforced with 10% PGA fibers (PLG-FR), increasing the stiffness of the implant by 20-fold. Confluent primary cultures of rat costochondral resting zone chondrocytes (RC) were loaded into PLG-H foams and implanted intramuscularly. To determine if growth factor pretreatment could modulate the ability of the cells to form new cartilage, RC cells were pretreated with recombinant human platelet derived growth factor-BB IPDGF-BB) for 4 or 24 h prior to implantation. To assess whether scaffold material properties could affect the ability of chondrogenic cells to form cartilage, RC cells were also loaded into PLG-FR scaffolds. To determine if the scaffolds or treatment with PDGF-BB affected the rate of chondrogenesis, tissue at the implant site was harvested at four and eight weeks post-operatively, fixed, decalcified and embedded in paraffin. Sections were obtained along the transverse plane of the lower leg, stained with haematoxylin and eosin, and then assessed by morphometric analysis for area of cartilage, area of residual implant, and area of fibrous connective tissue formation (fibrosis). Whether or not the cartilage contained hypertrophic cells was also assessed. The amount of residual implant did not change with time in any of the implanted tissues. The area occupied by PLG-FR implants was greater than that occupied by PLG-H implants at both time points. All implants were surrounded by fibrous connective tissue, whether they were seeded with RC cells or not. The amount of fibrosis was reduced at eight weeks for both implant types. When RC cells were present, the amount of fibrosis was less than seen in cell-free scaffolds. Pretreatment with PDGF-BB caused a slightly greater degree of fibrosis at four weeks than was seen if untreated cells were used in the implants. However, at eight weeks, if the cells had been exposed to PDGF-BB for 24 h, fibrosis was comparable to that seen associated with cell-free scaffolds. The cells supported an equivalent area of cartilage formation in both scaffolds. PDGF-BB caused a time-dependent decrease in cartilage formation at four weeks, but at eight weeks, there was a marked increase in cartilage formation in PDGF-BB-treated cells that was greatest in cells exposed for 4 h compared to those exposed for 24 h. Moreover, PDGF-BB decreased the formation of hypertrophic cells. The results indicate that in this model, RC cells produce cartilage; pretreatment of the RC cells with PDGF-BB promotes retention of a hyaline-like chondrogenic phenotype; and the material properties of the implant do not negatively impact on the ability of the cells to support chondrogenesis.

Animals↗
PubMed2000

Experimental investigations of the use of cartilage in tympanic membrane reconstruction.

BACKGROUND: Temporalis fascia, perichondrium, and cartilage are commonly used for reconstruction of the tympanic membrane in middle ear surgery. Cartilage grafts offer the advantage of higher mechanical stability, particularly in cases of chronic tubal dysfunction, adhesive processes, or total defects of the tympanic membrane, in contrast to fascia and perichondrium, which presumably offer better acoustic quality. HYPOTHESIS: The purpose of this study was to determine the acoustic transfer characteristics of cartilage of varying thickness and its mechanical deformation when exposed to fluctuations in atmospheric pressure. METHOD: Ten pairs of cartilage specimens from the cavum conchae and the tragus were obtained from fresh human cadavers. Young's modulus was determined by mechanical tension tests and statistically evaluated using the t test. The acoustic transfer characteristics of an additional 10 specimens were measured by a laser Doppler Interferometer after stimulation with white noise in an external auditory canal--tympanic membrane model. Mechanical stability was determined by measuring displacement of the cartilage using static pressure loads of < or = 4 kPa. RESULTS: Young's modulus determinations for conchal and tragal cartilage were 3.4 N/mm2 and 2.8 N/mm2, respectively, but the difference was not significant. Acoustic testing showed a 5-dB higher vibration amplitude in the midfrequency range for conchal compared with tragal cartilage, but the difference was not significant. Reducing cartilage thickness led to an improvement of its acoustic transfer qualities, with a thickness < or = 500 microm resulting in an acceptable acoustic transfer loss compared with the tympanic membrane. CONCLUSION: Both conchal and tragal cartilage are useful for reconstruction of the tympanic membrane from the perspective of their acoustic properties. The acoustic transfer loss of cartilage can be reduced by decreasing its thickness. A thickness of 500 microm is regarded as a good compromise between sufficient mechanical stability and low acoustic transfer loss.

Acoustic Stimulation↗
PubMed1999

Nonlinear analysis of cartilage in unconfined ramp compression using a fibril reinforced poroelastic model.

OBJECTIVE: To develop a biomechanical model for cartilage which is capable of capturing experimentally observed nonlinear behaviours of cartilage and to investigate effects of collagen fibril reinforcement in cartilage. DESIGN: A sequence of 10 or 20 steps of ramp compression/relaxation applied to cartilage disks in uniaxial unconfined geometry is simulated for comparison with experimental data. BACKGROUND: Mechanical behaviours of cartilage, such as the compression-offset dependent stiffening of the transient response and the strong relaxation component, have been previously difficult to describe using the biphasic model in unconfined compression. METHODS: Cartilage is modelled as a fluid-saturated solid reinforced by an elastic fibrillar network. The latter, mainly representing collagen fibrils, is considered as a distinct constituent embedded in a biphasic component made up mainly of proteoglycan macromolecules and a fluid carrying mobile ions. The Young's modulus of the fibrillar network is taken to vary linearly with its tensile strain but to be zero for compression. Numerical computations are carried out using a finite element procedure, for which the fibrillar network is discretized into a system of spring elements. RESULTS: The nonlinear fibril reinforced poroelastic model is capable of describing the strong relaxation behaviour and compression-offset dependent stiffening of cartilage in unconfined compression. Computational results are also presented to demonstrate unique features of the model, e.g. the matrix stress in the radial direction is changed from tensile to compressive due to presence of distinct fibrils in the model. RELEVANCE: Experimentally observed nonlinear behaviours of cartilage are successfully simulated, and the roles of collagen fibrils are distinguished by using the proposed model. Thus this study may lead to a better understanding of physiological responses of individual constituents of cartilage to external loads, and of the roles of mechanical loading in cartilage remodelling and pathology.

Biomechanical Phenomena↗
PubMed1996

Fibronectin fragment mediated cartilage chondrolysis. I. Suppression by anti-oxidants.

Fibronectin fragments damage cartilage in vitro by greatly enhancing metalloproteinases and suppressing proteoglycan (PG) synthesis which results in severe cartilage PG depletion. Since reactive oxygen species (ROS) have been implicated in catabolic cytokine action and preliminary data suggested that catabolic cytokines such as TNF-alpha, IL-1 alpha, IL-1 beta and IL-6 are responsible for fibronectin fragment mediated damage, selected anti-oxidants (AOs) were tested as inhibitors of cytokine. ROS and fibronectin fragment activity. Damage was measured by depletion of cartilage PG during tissue culture. The AO, N-acetylcysteine (NAC), decreased the extent of cartilage PG depletion caused by TNF-alpha and IL-1 alpha and by the ROS, hydrogen peroxide and superoxide anion, confirming that the cytokines operate through ROS and that ROS can initiate cartilage PG depletion. NAC at 0.1 and 1 mM, totally suppressed PG depletion caused by a highly potent amino-terminal 29-kDa fibronectin fragment (Fn-f) for 14 days in culture. NAC at 10 mM totally blocked Fn-f mediated PG depletion for 21 days and increased the cartilage PG content by 30% above normal levels. Glutathione (10 microM) and DMSO (1%) were also totally effective while catalase and superoxide decreased Fn-f mediated damage only during the first week and superoxide dismutase alone caused damage after 1 wk. The AOs caused protection by reducing the major catabolic activities of the Fn-f: enhanced release of stromelysin-1 (MMP-3) and suppression of PG and protein synthesis. NAC also decreased normal rates of PG degradation and increased the half-lives of labeled PG in both control and Fn-f treated cartilage. We conclude that the Fn-f mediates cartilage chondrolysis through ROS, consistent with the involvement of catabolic cytokines in the Fn-f mechanism, and that AOs greatly reduce Fn-f mediated cartilage chondrolysis. In an accompanying manuscript we also report that AOs promote reparative responses in Fn-f and cytokine treated cartilage.

Allopurinol↗
PubMed2001

The cartilage of the third eyelid: a comparative macroscopical and histological study in domestic animals.

The purpose of this comparative study was to evaluate morphological differences between the cartilages of the third eyelid in dogs, cats, pigs, cows, small ruminants and horses. For that reason a total of 83 third eyelids were investigated. By the aid of a modified maceration technique, the three-dimensional form of the cartilage could be demonstrated for the first time. Generally, the cartilage consists of a long narrow appendix which is followed by a variable crossbar. In dogs the appendix is cone shaped in the basal end and extends to form a triangular plate. The former is crescent-like in shape and has a marked bulge. The cartilage of the cat consists of an appendix which is enlarged in the proximal end as compared to the dog. The crossbar resembles a reverse s-form with ends tapering off to a point. In contrast pig and cow cartilage possess a typical anchorform whereas the cartilage of small ruminants starts with a thin rod which extends in a slightly curved form ending in an oval plate. The crossbar is crescent-like in these animals. In the horse the base of the cartilage is surrounded by a massive fatty tissue and the crossbar has a characteristic hook-form. Moreover, there are significant differences in regard to the quality of the cartilage, especially concerning the presence and distribution of elastic fibres. In cats and horses the elastic fibres of the adjacent connective tissue penetrate the perichondrium. Additionally, the centre of the cartilage shows a very dense network consisting of fine elastic fibres. In dogs, pigs, cows and small ruminants the cartilage consists of hyaline quality and only in the neighbouring connective tissue are some elastic fibres detectable.

Animals↗
PubMed2003

Validation of cartilage volume and thickness measurements in the human shoulder with quantitative magnetic resonance imaging.

OBJECTIVE: To validate quantitative magnetic resonance imaging (qMRI) for the assessment of cartilage volume and thickness in thin and curved cartilage layers, such as the shoulder. METHODS: Eight shoulder specimens from healthy individuals (aged 31-69 years) were investigated using a 3D gradient echo sequence with selective water excitation. After segmentation with a B-spline Snake algorithm, the cartilage volume and thickness were determined three dimensionally. The cartilage volume data were compared with water displacement of surgically removed tissue, and the thickness with A-mode ultrasound. RESULTS: The glenoid and humeral head cartilage volume from qMRI agreed highly with that from water displacement (systematic difference, +/-1 to +/-3%; absolute difference, 4 to 7%). For the cartilage thickness, the mean systematic difference ranged from -17% (mean cartilage thickness of the glenoid) to +7% (maximal cartilage thickness of the glenoid); the standard error of the estimate was 3.7% for the humeral head, and 6.4% for the glenoid. CONCLUSIONS: The applied technique can be used for accurate determination of cartilage volume and thickness in human joints with highly curved and thin cartilage layers, such as the shoulder. In vivo application of this method will depend on the development of efficient surface coils that allow high resolution imaging under in situ conditions.

Adult↗
PubMed2003

Ultrasound indentation of normal and spontaneously degenerated bovine articular cartilage.

OBJECTIVE: We have previously developed a handheld ultrasound indentation instrument for the diagnosis of cartilage degeneration. The instrument has been demonstrated to be capable of quantifying mechanical and acoustic properties of enzymatically degraded and normal bovine articular cartilage in vitro and in situ. The aim of this study was to investigate the sensitivity of the instrument to distinguish between normal and spontaneously degenerated (e.g., in osteoarthrosis) articular cartilage in vitro. DESIGN: Thirty articular cartilage samples were prepared from the bovine lateral patellae: 19 patellae with different degenerative stages and 11 patellae with visually normal appearance. Cartilage thickness, stiffness (dynamic modulus) and ultrasound reflection from the cartilage surface were measured with the handheld instrument. Subsequently, biomechanical, histological and biochemical reference measurements were conducted. RESULTS: Reproducibility of the measurements with the ultrasound indentation instrument was good. Standardized coefficient of variation was < or =6.1% for thickness, dynamic modulus and reflection coefficient. Linear correlation between the dynamic modulus, measured with the ultrasound indentation instrument, and the reference dynamic modulus was high (r=0.993, n=30, P<0.05). Ultrasound reflection coefficient, as determined from the cartilage surface, showed high linear correlations (typically r(2)>0.64, n=30, P<0.05) with the cartilage composition and histological or mechanical properties. The instrument was superior compared to visual evaluation in detecting tissue degeneration. CONCLUSION: This study indicates that the ultrasound indentation technique and instrument may significantly improve the early diagnosis of cartilage degeneration. The results revealed that visual evaluation is insensitive for estimating the structural and mechanical properties of articular cartilage at the initial stages of degeneration.

Animals↗
PubMed2003

The association of cartilage volume with knee pain.

OBJECTIVE: Whilst the characteristic pathologic feature of OA is the loss of hyaline cartilage, prior studies have demonstrated a poor relationship between severity of reported knee pain and degree of radiographic change. The aim of this study was to examine the association between knee symptoms and MRI cartilage volume. DESIGN: A cross-sectional study was performed to assess the association between knee symptoms and MRI cartilage volume in an unselected, community based population. The subjects were 133 postmenopausal females. The subjects had a T2-weighted fat saturated sagittal gradient-echo MRI performed of their right knee. Femoral, tibial and patella cartilage volumes were measured using three-dimensional (3D) Slicer, a software that facilitates semi-automatic segmentation, generation of 3D surface models and quantitative analysis. Qualitative data relating to symptoms, stiffness, pain, physical dysfunction and the quality of life using the WOMAC were recorded. The statistical analyses conducted to determine measures of association between knee pain/symptoms and cartilage volume were correlation, multiple regression and inter-quartile regression. RESULTS: Assessment of the association between patella cartilage volume and the WOMAC domains showed an inverse relationship between patella cartilage volume and pain, function and global score in a model including body mass index, physical activity and leg extensor power (all P=0.01). Inter-quartile regression comparing the lowest 25% with highest 25% patella cartilage volume demonstrated a stronger inverse relationship (P=0.005). CONCLUSION: This study suggests that alterations in patella volume are associated with pain, function and global scores of the WOMAC. In participants with more knee pain, there was an association with severity of patella cartilage reduction. Other MRI cartilage volume features were not strongly associated with WOMAC sub-scores.

Aged↗
PubMed1994

Analysis of collagens solubilized from cartilage of normal and spontaneously osteoarthritic rhesus monkeys.

Osteoarthritis (OA) is a disorder which results in the destruction of the articular cartilage and the remodeling of the subchondral bone in synovial joints. We have analyzed the cartilage collagen from normal and osteoarthritic free-ranging rhesus monkeys from the Cayo Santiago colony. The cartilage samples were assigned a severity score based on histological staging system and were divided into four groups (normals, mild OA, moderate OA and severe OA). After a 4.0 M guanidinium chloride (GuCl) extraction, the remainder of the cartilage was digested with pepsin and the collagen was salt precipitated at 2.5 M and 4.3 M NaCl. The GuCl solubility of the osteoarthritic cartilage increased compared to normals. Collagen extractability by GuCl also increased with the severity of disease. Pepsin digestion followed by salt precipitation shows that collagen from rhesus osteoarthritis cartilage is more easily extracted than from normal cartilage. With an anti-type I collagen antibody we have detected the presence of type I collagen in the severe OA cartilage samples but not in the milder OA groups or in normal cartilage. Total collagen content decreases with severity of OA, which is not due to changes in propyl hydroxylation because examination of collagen hydroxylation, based on hydroxyproline analysis, shows no difference between OA and normal cartilage.

Animals↗
PubMedDate not supplied

Comparison of butyl-2-cyanoacrylate, gelatin-resorcin-formaldehyde (GRF) compound and suture in stabilization of cartilage grafts in rabbits.

UNLABELLED: Cartilage grafting is an interesting option for rhinoplasties refinements. AIM: To compare butyl-2-cyanoacrylate, compound gelatin-resorcin-formaldehyde (GRF) and suture control to determine the efficacy of these tissue glue preparations in securing grafted cartilage. STUDY DESIGN: Experimental. METHODS: Fifteen male adult New Zealand rabbits were submitted to a surgical procedure to harvest 6 auricular cartilage grafts from each animal. 2 of these grafts in each animal were glued together with butyl-2-cyanoacrylate, 2 with compound gelatin-resorcin-formaldehyde and 2 sewn together with nylon suture. These sandwich grafts were then glued or sewn to the periosteum of the calvaria. After 2, 6 and 12 weeks, groups of 5 animals were sacrificed and histological analysis for inflammation was performed. Cartilage graft migration, adhesion and deformities of the grafts were also evaluated. RESULTS: There was less migration of the cartilages glued with GRF than with cyanoacrylate and suture. There was no statistical difference between the 3 materials of graft stabilization in relation to the inflammatory reaction in all evaluated periods. There wasn't detachment neither deformity in the cartilage sandwiches sewn with suture. The majority of detachment and deformed cartilages were found among those glued with cyanoacrylate. The number of deformed cartilages was directly related to the number of detached cartilages. The data were statistically significant (p< 0.05). CONCLUSION: The compound gelatin-resorcin-formaldehyde revealed to be a stabilization material for cartilage grafts in rabbits better than butyl-2-cyanoacrylate. The compound gelatin-resorcin-formaldehyde was also better than the suture when comparing its fixation to the periosteum.

Animals↗
PubMed2002

Site-specific immunostaining for type X collagen in noncalcified articular cartilage of canine stifle knee joint.

Type X collagen is a short-chain collagen that is strongly expressed in hypertrophic chondrocytes. In this study, we used an immunohistochemical technique exploiting a prolonged hyaluronidase unmasking of type X collagen epitopes to show that type X collagen is not restricted to calcified cartilage, but is also present in normal canine noncalcified articular cartilage. A 30 degrees valgus angulation procedure of the right tibia was performed in 15 dogs at the age of 3 months, whereas their nonoperated sister dogs served as controls. Samples were collected 7 and 18 months after the surgery and immunostained for type X collagen. The deposition of type X collagen increased during maturation from age 43 weeks to 91 weeks. In the patella, most of the noncalcified cartilage stained for type X collagen, whereas, in the patellar surface of the femur, it was present mainly in the femoral groove close to cartilage surface. In femoral condyles, the staining localized mostly in the superficial cartilage on the lateral and medial sides, but not in the central weight-bearing area. In tibial condyles, type X collagen was often observed close to the cartilage surface in medial parts of the condyles, although staining could also be seen in the deep zone of the cartilage. Staining for type X collagen appeared strongest at sites where the birefringence of polarized light was lowest, suggesting a colocalization of type X collagen with the collagen fibril arcades in the intermediate zone. No significant difference in type X collagen immunostaining was observed in lesion-free articular cartilage between controls and dogs that underwent a 30 degrees valgus osteotomy. In osteoarthritic lesions, however, there was strong immunostaining for both type X collagen and collagenase-induced collagen cleavage products. The presence of type X collagen in the transitional zone of cartilage in the patella, femoropatellar groove, and in tibial cartilage uncovered by menisci suggests that it may involve a modification of collagen fibril arrangement at the site of collagen fibril arcades, perhaps providing additional support to the collagen network.

Animals↗
PubMed2006

Predictive indicators for thyroid cartilage involvement in carcinoma of the larynx seen on spiral computed tomography scans.

OBJECTIVES: Recent studies have shown that the spiral computed tomography (CT) scan is a sensitive imaging modality for predicting neoplastic invasion of thyroid cartilage. The objectives of our study were: to assess the accuracy of pre-operative spiral CT in predicting thyroid cartilage involvement in patients with carcinoma of the larynx; and to elucidate the factors that would accurately indicate cartilage involvement. MATERIAL AND METHODS: Medical records, including spiral CT scans and pathological reports, were reviewed for 27 patients who had undergone laryngectomy in two major hospitals in south Wales. A consultant radiologist with special interest in cross-sectional imaging re-evaluated the scans to assess neoplastic involvement of the thyroid cartilage, based on definite, objective criteria. These criteria included: soft tissue asymmetry; loss of medullary space; spiky or irregular surface; distortion of cartilage framework; and abnormal soft tissue on both sides of the cartilage. The radiological findings were then correlated with the histopathological evidence of cartilage invasion by the tumour. RESULTS: Out of the 27 cases, 15 had evidence of histological invasion of thyroid cartilage. The most specific criterion to predict thyroid cartilage involvement was the presence of tumour on both sides of the cartilage (specificity of 91 per cent, sensitivity of 66 per cent). Combining two criteria increased both the sensitivity and the specificity to 86 and 91 per cent, respectively.

Carcinoma↗
PubMed2005

Gene-mediated restoration of cartilage matrix by combination insulin-like growth factor-I/interleukin-1 receptor antagonist therapy.

Combination of growth factor gene-enhanced cartilage matrix synthesis with interleukin-1 receptor antagonist protein (IL-1Ra) abrogation of cartilage matrix degradation may reduce and possibly reverse cartilage loss in synovitis and osteoarthritis. The feasibility of cotransduction of synovial membrane with two such genes that may act on cartilage homeostasis was investigated in an in vitro coculture system. Cultured synoviocytes in monolayer were cotransduced with E1-deleted adenoviral vectors, one containing IGF-I coding sequence under cytomegalovirus (CMV) promoter control (200 multiplicities of infection (moi)), and the second containing IL-1Ra sequence under CMV promoter control (100 moi). Adenovirus-IGF-I (AdIGF-I) transduction and AdIGF-I/AdIL-1Ra cotransduction of synovial monolayer cultures resulted in increased IGF-I mRNA and ligand expression, and similarly AdIL-1Ra and AdIGF-I/AdIL-1Ra-transduced cultures expressed high levels of IL-1Ra. Northern analysis confirmed a single mRNA transcript of the appropriate size for both IGF-I and IL-1Ra transgene expression. Synovial cell monolayer and cartilage explant coculture experiments were used to examine the effects of IGF-I and IL-1Ra protein expressed by transduced synoviocytes on normal and IL-1-depleted cartilage. Transduced monolayer cultures produced peak medium IGF-I content of 114+/-20.2 ng/ml and IL-1Ra levels of 241.8+/-10.5 ng/ml at 48 h after transduction. These IGF-I concentrations were sufficient to produce significantly increased proteoglycan (PG) content of normal cartilage cultured in medium conditioned by AdIGF-I and AdIGF-I/AdIL-1Ra-transduced synoviocytes. Interleukin-1-exposed cartilage was markedly depleted of PG, and this catabolic state was partially reversed in AdIGF-I-transduced cultures and fully reversed by AdIGF-I/AdIL-1Ra-transduced synovial cocultures. These data indicate that cultured synoviocytes are readily cotransduced by two recombinant adenoviral vectors containing transgenes active in restoring joint health. The AdIL-1Ra and AdIGF-I transgenes were abundantly expressed and the secreted products achieved therapeutic concentrations by day 2. The resulting increase in matrix biosynthesis returned cartilage PG content to normal levels. These data suggest that there may be significant value in cotransduction of synovial membrane to attenuate cartilage malacia associated with synovitis, injury, or early arthritis.

Adenoviridae↗
PubMed2000

Influence of interleukin-1beta and hyaluronan on proteoglycan release from equine navicular hyaline cartilage and fibrocartilage.

Proteoglycan (PG) release, in response to recombinant human interleukin-1beta (rh-IL-1beta), was measured in cartilage explants obtained from the equine distal sesamoid bone (navicular bone). Fibrocartilage from the surface of the navicular bone apposing the deep digital flexor tendon and hyaline cartilage from the surface of the navicular bone articulating with the middle phalanx were labelled with 35SO4. Hyaline cartilage from the distal metacarpus was used as a control tissue. Following radiolabel incorporation, the three cartilage types were treated with rh-IL-1beta (100 U/mL) in the presence of hyaluronan (0.2, 2, 20, 200 and 2000 microgram/mL). rh-IL-1beta-Induced PG release was measured by scintillation assay of PG-bound radiolabel. Increases in PG release of 94% (P < 0.01), 101% (P < 0.05) and 122% (P < 0.05), in response to rh-IL-1beta, were noted in fibrocartilage, navicular hyaline cartilage and metacarpal hyaline cartilage, respectively. Hyaluronan (0.2 microgram/mL) significantly reduced rh-IL-1beta-induced PG release in metacarpal hyaline cartilage (P < 0.01). In fibrocartilage and navicular hyaline cartilage, hyaluronan did not reduce PG release and at some concentrations appeared to increase PG release, although this was not statistically significant. These experiments show that (i) fibrocartilage and hyaline cartilage of the navicular bone release PGs in response to rh-IL-1beta, and (ii) hyaluronan does not prevent rh-IL-1beta-induced breakdown of navicular bone cartilage.

Adjuvants, Immunologic↗
PubMed1997

An ultrastructural study of cartilage resorption at the site of initial endochondral bone formation in the fetal mouse mandibular condyle.

An ultrastructural study was undertaken on cartilage resorption at the site of initial endochondral bone formation in the mouse mandibular condyle on d 16 of pregnancy. After resorbing the bone collar, the osteoclasts extended their cell processes into the cartilage matrix and made contact with hypertrophic chondrocytes. By means of cell processes or vacuolar structures, these osteoclasts entrapped the calcified cartilage matrices, cell debris, and the degraded uncalcified cartilage matrices. In particular, since the calcified cartilage matrices were sometimes seen to be disrupted within the osteoclastic vacuolar structures, they were probably disposed of by the osteoclasts. Invading endothelial cells giving rise to capillaries also directly surrounded the degraded uncalcified cartilage matrices and small deposits of cell debris. In addition, hypertrophic chondrocytes that had attached to or were in the process of attaching to the invading osteoclasts often enclosed the small calcified cartilage matrices. Other cell types that have often been reported in other regions of cartilage resorption were not seen at the site of initial endochondral bone formation in this study. Our findings in relation to cartilage resorption may therefore represent unique features of the site of initial endochondral bone formation site. We consider that the manner of cartilage resorption is likely to vary by site, age, and species.

Animals↗
PubMed1998

Transplantation of allograft chondrocytes embedded in agarose gel into cartilage defects of rabbits.

OBJECTIVE: Durable healing of full-thickness articular cartilage defects has been considered for a long time as a highly desirable, but unlikely event to occur. In recent years, conflicting reports on the outcome of in vitro and in vivo studies on chondrocyte and cartilage grafting into animal and human joints have raised new arguments for and against controlled repair of articular cartilage following injury. Some of the problems result from insufficient characterization of implant and repair tissue, and from too short follow up phases. Here we describe a new approach to repair articular cartilage defects in rabbit knees by allografting chondrocytes cultured in agarose gels. DESIGN: The implants were monitored over 6-18 months and graded histologically, immunohistochemically, and electron microscopically, using a grading scale based on seven evaluation criteria. Control implants of pure agarose produced poor fibrous substitute tissue, insufficient healing and incomplete filling of the cartilage defects. After transplantation of allogenic chondrocytes embedded in agarose, the quality of the newly formed repair cartilage was superior with respect to type II collagen and proteoglycan content and cellular architecture when compared with untreated defects. Superficial fibrillation and degradation were significantly diminished or prevented. RESULTS: New subchondral bone formed at the level of the previous subchondral bone. In most cases the repair tissue merged with the host articular cartilage; normal calcified cartilage was the only tissue zone that did not participate in the integration of the transplant. By gross evaluation 24% of grafts showed an extent of recovery never observed in controls. The best results were obtained after 18 months when 47% of the grafts (N = 15) developed a morphologically stable hyaline cartilage. CONCLUSION: These studies demonstrate that agarose-embedded chondrocyte may prove a valuable tool for controlled repair of articular cartilage defects.

Agar↗
PubMed1999

Altered mechanics of cartilage with osteoarthritis: human osteoarthritis and an experimental model of joint degeneration.

OBJECTIVE: Studies of cartilage mechanics seek to determine the fundamental relationships between mechanical behavior and the composition and structure of healthy cartilage and to determine mechanisms for changes associated with degeneration. METHOD: The mechanics of normal and osteoarthritic (OA) human articular cartilage are reviewed. Studies of the initiation and pathogenesis of cartilage degeneration in the anterior cruciate ligament transection (ACLT) model of joint instability are also presented. RESULTS: In human cartilage with OA, tensile, compressive and shear behaviors are dramatically altered. These changes present as decreases in the modulus or stiffness of OA cartilage in tension, compression and shear loading, and increases in the propensity to swell as compared to healthy cartilage. In the ACL transection model of OA, similar changes in the mechanics of cartilage have been observed. In addition, changes in structure, composition, and as metabolism consistent with human OA have been found. Deterioration of the collagen-proteoglycan solid network, which appears to be focused at the articular surface, has been the earliest cartilage changes in the model. It remains to be determined if the initial disruption of the cartilage surface is a direct result of mechanical forces or a product of altered chondrocyte activity. CONCLUSIONS: These data and continued research using experimental models of OA provide a basis for our understanding of the pathogenesis and the time course of events in OA and will lead to the development of better procedures for disease intervention and treatment.

Animals↗