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PubMed2006

Autologous cartilage implantation for full thickness articular cartilage defects of the knee.

BACKGROUND: Treatments for managing articular cartilage defects of the knee, including drilling and abrasion arthroplasty, are not always effective. When they are, long-term benefits may not be maintained and osteoarthritis may develop, resulting in the need for a total knee replacement. An alternative is the surgical implantation of healthy cartilage cells into damaged areas (autologous cartilage implantation). OBJECTIVES: To determine the effectiveness of autologous cartilage implantation (ACI) in people with full thickness articular cartilage defects of the knee. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (15 December 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2005), MEDLINE (1966 to December 2005), CINAHL (1982 to December Week 2, 2004), EMBASE (1988 to 2005 Week 50), SPORTDiscus (1830 to January 2005) and the National Research Register Issue 3, 2005. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing ACI with any other type of treatment (including no treatment or placebo) for symptomatic cartilage defects of the medial or lateral femoral condyle, femoral trochlea or patella. DATA COLLECTION AND ANALYSIS: Two review authors selected studies for inclusion independently. We assessed study quality based on adequacy of the randomisation process, adequacy of the allocation concealment process, potential for selection bias after allocation and level of masking. Data was not pooled due to clinical and methodological heterogeneity in the studies. MAIN RESULTS: We included four randomised controlled trials (266 participants). One trial of ACI versus mosaicplasty reported statistically significant results for ACI at one year, but only in a post-hoc subgroup analysis of participants with medial condylar defects; 88% had excellent or good results with ACI versus 69% with mosaicplasty. A second trial of ACI versus mosaicplasty found no statistically significant difference in clinical outcomes at two years. There was no statistically significant difference in outcomes at two years in a trial comparing ACI with microfracture. In addition, one trial of matrix-guided ACI versus microfracture did not contain enough long-term results to reach definitive conclusions. AUTHORS' CONCLUSIONS: The use of ACI and other chondral resurfacing techniques is becoming increasingly widespread. However, there is at present no evidence of significant difference between ACI and other interventions. Additional good quality randomised controlled trials with long-term functional outcomes are required.

Cartilage, Articular↗
PubMed1986

Metabolism of a cartilage matrix glycoprotein in normal and osteoarthritic canine articular cartilage.

We have recently described a 550,000-dalton noncollagenous cartilage matrix glycoprotein (CMGP), with subunits of 130,000, which is present in hyaline cartilage and fibrocartilage. Biosynthetic studies indicated that CMGP was synthesized by short-term organ cultures of normal canine articular cartilage, representing approximately 9% of the total 3H-leucine incorporated into protein in 24-hour cultures. There was no incorporation of 35S-sulfate or 3H-mannose into CMGP under these conditions, but the protein did incorporate 32P-phosphate. The majority of the 3H-leucine-labeled CMGP was removed after 24 hours of chase with unlabeled leucine, and only a small amount remained at 72 hours, which suggests that there was rapid metabolism of the protein. CMGP was not detected in cartilage after addition of cycloheximide to the culture medium; this confirms its short half-life. Cultures of osteoarthritic cartilage obtained from dogs 8-10 weeks after anterior cruciate ligament transection revealed no difference in the metabolism of CMGP in this tissue compared with that found in cultures of normal articular cartilage.

Animals↗
PubMed1995

The chondrocyte, architect of cartilage. Biomechanics, structure, function and molecular biology of cartilage matrix macromolecules.

Chondrocytes are specialised cells which produce and maintain the extracellular matrix of cartilage, a tissue that is resilient and pliant. In vivo, it has to withstand very high compressive loads, and that is explicable in terms of the physico-chemical properties of cartilage-specific macromolecules and with the movement of water and ions within the matrix. The functions of the cartilage-specific collagens, aggrecan (a hydrophilic proteoglycan) and hyaluronan are discussed within this context. The structures of cartilage collagens and proteoglycans and their genes are known and a number of informative mutations have been identified. In particular, collagen fibrillogenesis is a complex process which can be altered by mutations whose effects fit what is known about collagen molecular structural functions. In other instances, mutations have indicated new functions for particular molecular domains. As cartilage provides the template for the developing skeleton, mutations in genes for cartilage-specific proteins often produce developmental abnormalities. The search for mutations amongst such genes in heritable disorders is being actively pursued by many groups, although mutation and phenotype are not always well correlated, probably because of compensatory mechanisms. The special nature of the chondrocyte is stressed in connection with its cell involvement in osteoarthritis, the most widespread disease of diarthrodial joints.

Animals↗
PubMed2004

dGEMRIC (delayed gadolinium-enhanced MRI of cartilage) indicates adaptive capacity of human knee cartilage.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a new imaging technique to estimate joint cartilage glycosaminoglycan content by T1-relaxation time measurements after penetration of the hydrophilic contrast agent Gd-DTPA(2-). This study compares dGEMRIC in age-matched healthy volunteers with different levels of physical activity: Group 1 (n = 12): nonexercising individuals; Group 2 (n = 16): individuals with physical exercise averaging twice weekly; Group 3 (n = 9): male elite runners. dGEMRIC was performed 2 hr after an intravenous injection of Gd-DTPA(2-) at 0.3 mmol/kg body weight. T1 differed significantly between the three different levels of physical exercise. T1 values (mean of medial and lateral femoral cartilage) for Groups 1, 2, and 3 were: 382 +/- 33, 424 +/- 22 and 476 +/- 36, respectively (ms, mean +/- SD) (P = 0.0004, 1 vs. 2 and 0.0002, 2 vs. 3). Irrespective of the exercise level, T1 was longer in lateral compared to medial femoral cartilage (P = 0.00005; n = 37). In conclusion, this cross-sectional study indicates that human knee cartilage adapts to exercise by increasing the glycosaminoglycan content. Furthermore, results suggest a compartmental difference within the knee with a higher glycosaminoglycan content in lateral compared to medial femoral cartilage. A higher proportion of extracellular water, i.e., larger distribution volume, may to some extent explain the high T1 in the elite runners.

Adult↗
PubMed1986

Degradation of cartilage matrix by purified elastase and its control by an endogenous purified specific cartilage elastase inhibitor.

UNLABELLED: We report here that an endogenous protein in cartilage is capable of inhibiting leukocyte elastase degradation of cartilage matrix. This inhibitor is specific for elastase. After 30 min of incubation, small amounts of the purified elastase are capable of releasing relatively large amounts of uronic acid positive material and relatively small amounts of collagenous and noncollagenous protein. The hydrolytic effectiveness of elastase is exemplified by its action on various natural substrates. This action, however, is inhibited by a specific natural elastase inhibitor purified from cartilage. INTRODUCTION: The extracellular matrix of cartilage is responsible for the resiliency, tensile strength plus ion and water binding ability of this tissue. Any modification in the arrangement or composition of proteoglycans, collagen and glycoproteins found in the cartilage matrix affects these properties. Such modification can be derived by the action of hydrolytic enzymes originating from chrondrocytes or from cells attracted in the cartilage area by chemotaxis.

Animals↗
PubMed1981

Staining of demineralized cartilage. II. Quantitation of articular cartilage proteoglycan after fixation and rapid demineralization.

Safranin O in the orthochromatic form stains articular cartilage proteoglycan quantitatively in histological sections of demineralized cartilage. This was shown by scanning microdensitometry of stained sections of undemineralized and demineralized articular cartilage and by biochemical analysis of 35S labelled cartilage subjected to demineralization. In contrast, Alcian Blue staining is affected by unknown factors other than simply the amount of proteoglycan present. Alcoholic formalin fixes articular cartilage proteoglycan more successfully than formol Zenker for subsequent rapid demineralization. Alcoholic formalin does not preserve cellular appearance as well as formol Zenker. Staining of articular cartilage with PAS appears unaffected by demineralization.

Aged↗
PubMed1982

Comparative study on glycosaminoglycan-sulfotransferases in rat costal cartilage and chick embryo cartilage.

1. The comparative features of glycosaminoglycan-sulfotransferase system in rat costal cartilage and chick-embryo cartilage were examined. Some different properties of glycosaminoglycan-sulfotransferases in the cartilage of both the animals have been observed. 2. This study shows that rat costal cartilage contains more 4-sulfotransferase than 6-sulfotransferase and that that reverse situation pertains to chick-embryo cartilage, although both the rat and chick-embryo cartilage contain two sulfotransferase species. 3. Our preliminary experiments by use of rat sulfotransferases and chick endogenous acceptor or of chick sulfotransferases and rat sulfotransferases and chick endogenous acceptor or of chick sulfotransferases and rat endogenous acceptor suggest that sulfotransferases in a given tissue play a central role in determining which sites of the N-acetylgalactosamine moiety of chondroitin sulfates occurring in the tissue are sulfated.

Animals↗
PubMed2006

Maturation-dependent change and regional variations in acoustic stiffness of rabbit articular cartilage: an examination of the superficial collagen-rich zone of cartilage.

OBJECTIVE: The purpose of the study was to investigate maturation-dependent changes of acoustic (ultrasound) stiffness and other ultrasound features of articular cartilage in healthy rabbit knees. METHODS: Five groups of rabbits of various ages (3 weeks, 8 weeks, 6 months, 1 year, 2.5 years) consisting of five rabbits per group were examined. Signal intensity (index of stiffness), signal duration (index of surface irregularity) and interval between signals (index of thickness) of the ultrasound reflection from articular cartilage were examined at four sites: posterior lateral femoral condyle, posterior medial femoral condyle, lateral tibial plateau, and medial tibial plateau. The sites were observed macroscopically and microscopically with a light microscope and a polarized light microscope. RESULTS: At the lateral and medial condyles and the lateral tibial plateau, signal intensity was least in 3-week-old specimens. The intensity increased until 6 months or 1 year of age. At these sites, the signal durations and intervals between signals were least at the ages of 6 months or 1 year. At the medial tibial plateau, the intensity was the least at 2.5 years of age and the interval between signals was least at 3 weeks of age; there was no effect of age on signal duration. Cartilage surfaces of all specimens were smooth and no degenerative changes were macroscopically or microscopically evident. The surface brightness of cartilage under the polarized light microscope was consistent with signal intensity values. CONCLUSIONS: The response of articular cartilage to ultrasound was maturation-dependent. Acoustic properties differed from mechanical stiffness properties, which were determined using indentation. Ultrasound may detect properties of the surface collagen of the articular cartilage.

Aging↗
PubMed1986

Stereological studies on the epiphyseal growth cartilage and characterization of costal cartilage proteoglycans in the achondroplastic (cn/cn) mouse.

The achondroplastic mouse is a dwarf mouse in which the endochondral growth of the skeleton is disturbed. The main morphological characteristic of the affected growth cartilage is an underdeveloped hypertrophic zone. The pattern of matrix mineralization seems to be unaffected, even in areas where hypertrophic chondrocytes are completely absent. The present stereological results indicate a disturbance of the cn/cn cartilage already in the proliferative zone. At the electron microscopical level a clearly abnormal spatial distribution of matrix vesicles was observed in the affected growth cartilage. The vesicle concentration of the cn/cn cartilage was increased, but the mineralizing cartilage showed a decrease of vesicles similar to that in the normal tissue. Parallel biochemical characterization of the proteoglycans and glycosaminoglycans of the cn/cn costal cartilage revealed normal conditions, also in the growth region, which was sampled as a separate tissue fraction. Thus the biochemical results provide no evidence of disturbed glycosaminoglycan metabolism.

Achondroplasia↗
PubMed2001

Use of synovial fluid markers of cartilage synthesis and turnover to study effects of repeated intra-articular administration of methylprednisolone acetate on articular cartilage in vivo.

In vivo the effects of intra-articular (IA) corticosteroids on articular cartilage remain controversial. This study was designed to examine this issue using synovial fluid (SF) markers of cartilage metabolism. Paired radiocarpal joints, without clinical or radiographic signs of joint disease, were studied in 10 adult horses. Aseptic arthrocentesis was performed weekly for 13 weeks. IA injections of methylprednisolone acetate (MPA) into the treatment joint and the vehicle into the control joint were performed at weeks 3, 5 and 7. We used radioimmunoassays on SF samples which measure a keratan sulfate epitope (KS) and the 846 epitope on cartilage aggrecan (PG) and the C-propeptide (CPII) of cartilage type II procollagen which is released following synthesis of this molecule. Gel chromatography was performed on selected SF samples to evaluate the sizes of SF PG molecules. The total joint KS and the 846 epitopes were both present on a heterogeneous population of mainly molecules which, from chromotographic analysis, appeared to be mainly fragments of the articular cartilage aggrecan. They were significantly elevated in MPA joints whereas CPII was significantly reduced compared to the control during the treatment period. These results indicate that the repeated use of IA MPA leads to a potentially harmful inhibition of procollagen II synthesis and an increased release of degradation products of the PG aggrecan from articular cartilage.

Aggrecans↗
PubMed1998

Ageing and zonal variation in post-translational modification of collagen in normal human articular cartilage. The age-related increase in non-enzymatic glycation affects biomechanical properties of cartilage.

A biomechanical failure of the collagen network is postulated in many hypotheses of the development of osteoarthritis with advancing age. Here we investigate the accumulation of non-enzymatic glycation (NEG) products in healthy human articular cartilage, its relation to tissue remodelling and its role in tissue stiffening. Pentosidine levels were low up to age 20 years, and increased linearly after this age. This indicates extensive tissue remodelling at young age, and slow turnover of collagen after maturity has been reached. The slow remodelling is supported by the finding that enzymatic modifications of collagen (hydroxylysine, hydroxylysylpyridinoline, and lysylpyridinoline) were not related to age. The high remodelling is supported by levels of the crosslink lysylpyridinoline (LP) as a function of distance from the articular surface. LP was highest at the surface in mature cartilage (>20 years), whereas in young cartilage (<10 years) the opposite was seen; highest levels were close to the bone. LP levels in cartilage sections at age 14 years are high at the surface and close to the bone, but they are low in the middle region. This indicates that maturation of cartilage in the second decade of life starts in the upper half of the tissue, and occurs last in the tissue close to the bone. The effect of NEG products on instantaneous deformation of cartilage was investigated as a functional of topographical variations in pentosidine levels in vivo and in relation to in vitro induced NEG. Consistently, higher pentosidine levels were associated with a stiffer collagen network. A stiffer and more crosslinked collagen network may become more brittle and more prone to fatigue.

Adult↗
PubMed1998

A novel cartilage protein (CILP) present in the mid-zone of human articular cartilage increases with age.

A novel, somewhat basic noncollagenous protein was purified from guanidine hydrochloride extracts of human articular cartilage using cesium chloride density gradient centrifugation, followed by ion-exchange chromatography at pH 5, and gel filtration on two serially coupled columns of Superose 6 and Superdex 200. The protein of 91.5 kDa contains a single polypeptide chain substituted with N-linked oligosaccharides. It appeared unique to cartilage as studied by enzyme-linked immunosorbent assay and immunoblots of various tissue extracts. Its concentration in articular cartilages showed some variability with age being lower in young individuals. It represents a chondrocyte product, since it is synthesized by articular chondrocytes in explant cultures. Interestingly, the distribution of the protein in the articular cartilage provides important information on the nature of chondrocytes at different compartments in the tissue. Thus, chondrocytes in the middle/deeper layers of the tissue in particular, appeared to have produced the protein and deposited it in the interterritorial matrix. The protein was neither seen in the superficial nor in the deepest regions of the articular cartilage. Based on its immunolocalization we have named this protein CILP (cartilage intermediate layer protein).

Adolescent↗
PubMed1993

Osteoarthritic human cartilage is more sensitive to transforming growth factor beta than is normal cartilage.

Osteoarthritis is a degenerative joint disease, characterized by the destruction of the articular cartilage. One of the first changes in the osteoarthritic articular cartilage is a reduction in proteoglycan content. In this study we demonstrate that transforming growth factor beta (TGF beta), a multi-functional growth factor, stimulates the proteoglycan synthesis of explants from human articular knee cartilage dose-dependently in vitro. Osteoarthritic cartilage proved to be much more sensitive to stimulation by TGF beta than normal healthy cartilage. This may indicate that TGF beta plays an important role in the repair of osteoarthritic cartilage.

Aged↗
PubMed2000

Total reconstruction of the alar cartilages with a partially split septal cartilage graft.

The alar cartilage is a unique structure that supports the tip of the nose, keeps the external valve open, and plays an important role in tip aesthetics. Very often the plastic surgeon needs to reconstruct this cartilage, as in secondary rhinoplasties when the lower lateral cartilage is overresected. Many authors have described cartilage grafts taken from the ear and septum, mounted and stitched in various manners, with some very good results. In patients with thin skin, though, any irregularity or distortion in the grafts becomes visible after a short time postoperatively. The authors present an alternative to reconstructing alar cartilage symmetrically using one graft. This graft is obtained by shaping septal cartilage in an "L" form, with a 135-deg angle (instead of a 90-deg angle) between its legs, and then splitting the smaller leg, obtaining a strut from the longer leg and two "lateral crura" from the shorter leg.

Cartilage↗
PubMed1995

Total reconstruction of the alar cartilage en bloc using the ear cartilage: a study in cadavers.

To determine whether the lamina tragi, isthmus, and cavum conchae are a donor area for reconstruction of the alar cartilage with all its elements (medial crus, junction of the medial and lateral crura, and lateral crus), with the same dimension and en bloc, 40 alar cartilages and 40 lower parts of ear cartilages of 20 cadavers were dissected. Several measurements were taken in the alar cartilages, such as distance, thickness, and angle. Then they were compared with the measurements performed in the ear cartilages and segments removed from the lamina tragi, isthmus, and cavum conchae. This study, done with cadavers, shows that from the lamina tragi, isthmus, and cavum conchae, en bloc resection is possible with characteristics of form and dimension similar to those of the homolateral alar cartilage. The segment removed en bloc from the intermediate part of the lamina tragi, isthmus, and cavum conchae replaces, respectively, the medial crus, junction of the medial and lateral crura, and lateral crus.

Adult↗
PubMed1997

Internal stabilization of autogenous rib cartilage grafts in rhinoplasty: a barrier to cartilage warping.

Autogenous rib cartilage grafts have gained more widespread use in rhinoplasty as dorsal onlay grafts and columellar struts. However, the usefulness of rib as a donor site has been limited by difficulties with postoperative cartilage warping. We hypothesized that the internal stabilization of rib cartilage grafts with Kirschner wires would prevent warping. The costochondral cartilages of a fresh cadaver were harvested and carved into 4 x 10 x 40 nm blocks. A single 0.035-in K-wire was placed longitudinally into the center of each of the study specimens (n = 9), whereas no internal stabilization was utilized in the control group (n = 9). Over a 10-day study period, a mean of 2.2 degrees of warping was observed in the grafts with K-wires as compared to 8.9 degrees in the control group. This indicates that internal stabilization of rib grafts significantly reduces warping (p < 0.001). In a subsequent clinical study, 28 patients underwent placement of internally stabilized columellar struts (n = 19) and/or dorsal nasal grafts (n = 12) using autogenous rib cartilage. At a mean follow-up of 13.5 months (range 3 to 36 months), graft warping was not observed in any patient. Satisfactory aesthetic results were achieved in all but one patient, in whom mild displacement of a dorsal onlay graft occurred. Palatal extrusion of the K-wire occurred in 3 of the first 9 columellar struts. This prompted an alteration in technique with no subsequent extrusions. We conclude that the internal stabilization of autogenous rib cartilage grafts with K-wires effectively prevents graft warpage.

Adult↗
PubMed1993

Human facet cartilage: swelling and some physicochemical characteristics as a function of age. Part 2: Age changes in some biophysical parameters of human facet joint cartilage.

This study was aimed at investigating, in relating to aging, some of the biochemical and biophysical characteristics of the facet cartilage that determine the functional behavior of this tissue. In addition, facets and discs from the same segment were graded according to their macroscopic appearance. The proportion of severely degenerate discs was low in young subjects and increased with age; by contrast, the proportion of coarsely fibrillated and/or ulcerated facets was high in spines from young adults and remained constant throughout adulthood. Unlike discs, facets do not show an age-related loss of proteoglycans or a consequent decrease in the resistance to a compressive load. However, even in relatively young age groups (30-50 years) a high hydration was observed more often in facet joints than in cartilage from other joints studied. These characteristics are known to accompany damage of the collagen network and cartilage degeneration. Unlike normal femoral head cartilage, facet cartilage does not show a rise in fixed charge density with age. The cartilage from the superior processes (concave) is thicker than that from the inferior processes (convex) and has a higher fixed charge density. At the same time it has a higher water content, which indicates that damage occurs more frequently.

Adolescent↗
PubMed1992

Healing of full-thickness cartilage compared with full-thickness cartilage and subchondral bone defects in the equine third carpal bone.

The effect of lesion depth on the quality of third carpal bone cartilage repair was examined. A 1-cm diameter articular defect penetrating the calcified cartilage in one limb and the subchondral bone plate in the opposite limb was created in the radial facet of the third carpal bones. Clinical and xeroradiographic examinations were performed every 4 weeks until 4 months (3 horses) and 6 months (3 horses) after surgery. The synovial membrane, non-opposing articular surfaces and articular defects were examined grossly, histologically and histochemically. Grossly, deeper defects contained thicker, whiter tissue, but both joints contained generalised degenerative changes. Defects extending through calcified cartilage were filled deeply by fibrocartilage and superficially by fibrous connective tissue. Defects extending through subchondral bone were consistently filled with hyaline-like cartilage in the depths of the lesion, fibrocartilage in the intermediate layer and fibrous connective tissue superficially. The results indicate that subchondral bone is the source of hyaline-like cartilage repair tissue and suggest that quality of healing of cartilage defects may be improved by penetrating the subchondral bone plate. It also appears that the synovitis associated with the procedure must be controlled before the procedure can be advocated for treatment of clinical cases.

Animals↗