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PubMed2005

Articular cartilage adjacent to experimental defects is subject to atypical strains.

We tested the hypothesis that articular cartilage adjacent to experimental osteochondral defects is not subject to unusual strains under load. A 2.5-mm drill hole was made in the medial femoral condyle of 15 knees from 10 adult rabbits. Experimental joints were loaded with simulated quadriceps force, then frozen under load and preserved by freeze-substitution fixation. Deformation in the region of the defect was evaluated by scanning electron and light microscopy and compared with nondrilled and nonloaded control knees. To simulate blood clot, alginate was placed into some defects before loading. In loaded knees, articular cartilage at the edge of the drill hole was abnormally flattened and folded into the defect. Opposing tibial cartilage or meniscus intruded into the femoral defect beyond the cement line. Alginate did not prevent incursion of opposing cartilage. In this standard drill-hole model, the articular cartilage defect is occupied by the opposing surface when a joint is loaded. Any tissue growing or surgically implanted in the defect is subject to loading and displacement, therefore complicating attempts to characterize the healing or regenerative potential in similar drill-hole models. Deformation of cartilage at the defect edge suggests load concentration or increased compliance. Either phenomenon would contribute to subsequent degeneration of the cartilage adjacent to defects.

Animals↗
PubMed1990

Low molecular weight serine proteinase inhibitors of human articular cartilage. Isolation, characterization, and biosynthesis.

The major low molecular weight serine proteinase inhibitor of human articular cartilage was purified to homogeneity as determined by single-peak elution with 4 high resolution techniques. The purified protein was found to be a potent inhibitor of human leukocyte elastase and cathepsin G, as well as the native serine proteinases derived from human articular cartilage and intervertebral disc. The inhibitor and lysozymes were synthesized by human articular cartilage in vitro. These properties and the ability of this cationic inhibitor to bind to cartilage matrix components suggest a possible role in the modulation of matrix catabolism in normal and pathologic states.

Amino Acids↗
PubMed1982

Abnormal softening in articular cartilage: its relationship to the collagen framework.

Abnormal softening in articular cartilage is related to the presence of collagen fibers strongly aligned in a radial direction. In this paper, a morphologic model is proposed that provides a mechanism by which these radial arrays can develop passively from the more random, 3-dimensional network of fibers observed in normal articular cartilage.

Animals↗
PubMed1999

Functional analysis of articular cartilage deformation, recovery, and fluid flow following dynamic exercise in vivo.

The function of articular cartilage depends on the interaction between the tissue matrix and the interstitial fluid bound to the proteoglycan molecules. Mechanical loading has been shown to be involved in both the metabolic regulation of chondrocytes and in matrix degeneration. The purpose of the present study was therefore to analyze the deformation, recovery, and fluid flow in human articular cartilage after dynamic loading in vivo. The patellae of 7 volunteers were imaged at physical rest and after performing knee bends, with a specifically optimized fat-suppressed FLASH-3D magnetic resonance (MR) sequence. To measure cartilage deformation, the total volume of the patellar cartilage was determined, employing 3D digital image analysis. Patellar cartilage deformation ranged from 2.4 to 8.6% after 50 knee bends, and from 2.4% to 8.5% after 100 knee bends. Repeated sets of dynamic exercise at intervals of 15 min did not cause further deformation. After 100 knee bends, the cartilage required more than 90 min to recover from loading. The rate of fluid flow during relaxation ranged from 1.1 to 3.5 mm(3)/min (0.08 to 0.22 mm(3)/min per square centimeter of the articular surface) and was highly correlated with the individual degree of deformation after knee bends. The data provide the first quantification of articular cartilage recovery and of the rate of fluid flow between the cartilage matrix and surrounding tissue in intact joints in vivo. Measurement in the living opens the possibility of relating interindividual variations of mechanical cartilage properties to the susceptibility of developing joint failure, to assess the load-partitioning between the fluid phase and solid cartilage matrix during load transfer, and to determine the role of mechanically induced fluid flow in the regulation of the metabolic activity of chondrocytes.

Adult↗
PubMed2006

Collagen synthesis of articular cartilage explants in response to frequency of cyclic mechanical loading.

Articular cartilage in vivo experiences the effects of both cell-regulatory proteins and mechanical forces. This study has addressed the hypothesis that the frequency of intermittently or continuously applied mechanical loads is a critical parameter in the regulation of chondrocyte collagen biosynthesis. Cyclic compressive pressure was applied intermittently to bovine articular cartilage explants by using a sinusoidal waveform of 0.1-1.0 Hz frequency with a peak stress of 0.5 MPa for a period of 5-20 s followed by a load-free period of 10-1,000 s. These loading protocols were repeated for a total duration of 6 days. In separate experiments, cyclic loading was continuously applied by using a sinusoidal waveform of 0.001-0.5 Hz frequency and a peak stress of 1.0 MPa for a period of 3 days. Unloaded cartilage discs of the same condyle were cultured in identically constructed loading chambers and served as controls. We report quantitative data showing that (1) no correlation exists between the relative rate of collagen synthesis expressed as the proportion of newly synthesized collagen among newly made proteins and either the frequency of intermittently or continuously applied loads or the overall time cartilage is actively loaded, and (2) individual protocols of intermittently applied loads can reduce the relative rate of collagen synthesis and increase the water content, whereas (3) continuously applied cyclic loads always suppress the relative rate of collagen synthesis compared with that of unloaded control specimens. The results provide further experimental evidence that collagen metabolism is difficult to manipulate by mechanical stimuli. This is physiologically important for the maintainance of the material properties of collagen in view of the heavy mechanical demands made upon it. Moreover, the unaltered or reduced collagen synthesis of cartilage explants might reflect more closely the metabolism of normal or early human osteoarthritic cartilage.

Animals↗
PubMed1977

[Experimental and clinical aspects of the living articular cartilage transplantation and half-joint transplantation (author's transl)].

The articular cartilage transplantation and the half-joint transplantation necessitate the assessment of specific biological-transplantation questions as to the structure and function of the hyaline cartilage. Compared with other organ transplantations biometric and biomechanical factors have to be taken into consideration additionally. Up to now contradictory results were obtained in the animal experiment. On principle a survival of grafted non-preserved parts of cartilage seems to be possible. In clinical practice therapeutic trials for autogenous reimplantation of articular cartilage, autogenous joint surface partial transplantations and half-joint transplantations are justified. Allogenous half-joint transplantations may also be possible in exceptional cases.

Adolescent↗
PubMedDate not supplied

Measurement of articular cartilage stiffness of the femoropatellar, tarsocrural, and metatarsophalangeal joints in horses and comparison with biochemical data.

OBJECTIVE: To determine normal cartilage stiffness values in different weight-bearing and non-weight-bearing areas of 3 different equine joints, and to evaluate the relationship between cartilage stiffness and glycosaminoglycan (GAG) and collagen content. STUDY DESIGN: Compressive stiffness of the articular cartilage was measured in 8 horse cadaver femoropatellar (FP), tarsocrural (TC), and metatarsophalangeal (MT) joints. Gross evaluation, collagen content, GAG content, and histologic appearance were assessed for each measurement location. ANIMALS: Eight equine cadavers (4 intact females, 4 castrated males; 7 Quarter Horse or Quarter Horse type, 1 Arabian; aged 4-12 years, weighing 400-550 kg). METHODS: The articular surfaces of 8 equine cadaver FP, TC, and MT joints were grossly evaluated for signs of articular cartilage pathology. Stiffness at preselected sites (FP joint-6 sites; TC joint-3 sites; MT joint-4 sites) was determined using an arthroscopic indentation instrument. Biochemical composition (collagen, GAG content) and histologic evaluation (modified Mankin score) were assessed for each measurement site. RESULTS: All cartilage from all sites evaluated was determined to be normal based on macroscopic and histologic assessments. No significant correlation between Mankin scores and cartilage stiffness values was observed. Site differences in cartilage stiffness were measured in all 3 joints (P<.001). GAG or collagen content had a significant positive correlation with stiffness values in 6 of 13 sites (P<.05, r>0.622, r2>0.387). CONCLUSION: Relative cartilage stiffness values measured in healthy equine joints are site dependent and can be measured using an indentation device intended for arthroscopic application. CLINICAL RELEVANCE: An indentation instrument provided an objective means of determining relative compressive stiffness of articular cartilage. Further research needs to be performed to confirm the site and joint differences observed in this study in clinically normal horses and to determine if the tester can be used clinically to predict articular cartilage pathology.

Animals↗
PubMed1992

Normal human synovial fluid and articular cartilage contain similar intact proteoglycans.

This work, directed to characterization of proteoglycans present in normal human synovial fluid by Western blotting techniques, revealed an intimate relationship of these proteoglycans to those of articular cartilage. Analyses were performed on samples subjected to digestion with chondroitinase ABC, in the presence or absence of keratanase, yielding products containing core proteins with glycosaminoglycan side chain stubs. The proteoglycan core proteins contained epitopes reactive with monoclonal antibodies that distinguish between chondroitin sulfate-4 and chondroitin sulfate-6. Additionally, these products reacted with monoclonal antibody to keratan sulfate when keratanase was omitted from the digestion. The analysis of synovial fluid revealed that the proteoglycan core proteins expressed predominantly the chondroitin sulfate-6 epitope, with expression of the chondroitin sulfate-4 epitope demonstrable only in prepubertal individuals. There was coexpression of both chondroitin sulfate epitopes in all proteoglycan core proteins of prepubertal individuals. Coexpression of chondroitin sulfate and keratan sulfate epitopes occurred in all proteoglycan core proteins. Proteoglycan core proteins had M(r) similar to those obtained from articular cartilage. Hence, in individuals free of joint disease, most proteoglycans seem to be transferred from articular cartilage to the synovial fluid without major alteration in the apparent size of the proteoglycan core protein. Only a minor set of proteoglycan core proteins had no direct articular cartilage equivalent. As this set also contained keratan sulfate, it is likely to be of articular cartilage origin, but probably modified by proteolysis.

Adolescent↗
PubMed1983

Structure of proteoglycans from different layers of human articular cartilage.

Full-depth plugs of adult human articular cartilage were cut into serial slices from the articular surface and analysed for their glycosaminoglycan content. The amount of chondroitin sulphate was highest in the mid-zone, whereas keratan sulphate increased progressively through the depth. Proteoglycans were isolated from each layer by extraction with 4M-guanidinium chloride followed by centrifugation in 0.4M-guanidinium chloride/CsCl at a starting density of 1.5 g/ml. The efficiency with which proteoglycans were extracted depended on slice thickness, and extraction was complete only when cartilage from each zone was sectioned at 20 microns or less. When thick sections (250 microns) were extracted, hyaluronic acid was retained in the tissue. Most of the proteoglycans, extracted from each layer under optimum conditions, could interact with hyaluronic acid to form aggregates, although the extent of aggregation was less in the deeper layers. Two pools of proteoglycan were identified in all layers by gel chromatography (Kav. 0.33 and 0.58). The smaller of these was rich in keratan sulphate and protein, and gradually increased in proportion through the cartilage depth. Chondroitin sulphate chain size was constant in all regions. The changes in composition and structure observed were consistent with the current model for hyaline-cartilage proteoglycans and were similar to those observed with increasing age in human articular cartilage.

Adult↗
PubMed1999

[Indication for and performance of articular cartilage drilling using the Pridie method].

Articular cartilage has only a small capacity for regneration. This makes the repair of articular surfaces difficult. In 1959 Pridie described his method of resurfacing osteoarthritic knee joints. This operation is still in widespread use today. Pridie introduced the principle of drilling exposed subchondral bone with the objective of encouraging a fibro-cartilaginous repair. The newly formed fibrocartilaginous layer that develops over the lesion in osteoarthritis may be enough to decrease patients symptoms. Bone drilling into the subchondral layer is also effective in promoting healing of osteochondrosis dissecans. The choice of the treatment should be based on factors such as age of the patient, serverity of symptoms, activity level and functional demands on the joint, site and stage of the lesion. The drilling operation remains useful in osteoathritis and osteochondrosis dissecans.

Bone Regeneration↗
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↗
PubMed2000

Physicochemical properties of normal articular cartilage and its MR appearance.

Basic physical and physicochemical properties of articular cartilage are correlated with the MR parameters of this tissue. From these parameters, the typical appearance of cartilage in MR images is deduced. Some practical implications for clinical utilization of MRI of articular cartilage are summarized.

Cartilage, Articular↗
PubMed2000

Assessment of articular cartilage of the lateral tibial plateau in varus osteoarthritis of the knee.

This study describes the soft X-ray examinations of 24 lateral tibial plateaus obtained during total knee arthroplasty for varus osteoarthritis. The average thickness of the articular cartilage was 3.5 min and ranged from 2.1 to 5.0. We considered that 21 out of the 24 lateral tibial plateaus had well preserved articular cartilage. Within the well preserved articular cartilage, bony protuberances of various sizes were found in five cases. All lateral tibial plateaus except one showed osteophyte formation. We considered that 12 of the 24 lateral tibial plateaus had large osteophytes. Ten of these 12 lateral tibial plateaus had well preserved articular cartilage. Large osteophyte formation may not necessarily be a contra-indication of high tibial osteotomy (HTO) or unicompartmental knee arthroplasty (UKA). Cases with a bony protuberance may not be suitable for HTO or UKA, because the overlying articular cartilage is thin and inadequate for supporting load.

Journal Article↗
PubMed1998

Removal of proteoglycans from the surface of defects in articular cartilage transiently enhances coverage by repair cells.

Lesions within the articular cartilage layer of synovial joints do not heal spontaneously. Some repair cells may appear, but their failure to become established may be related to problems of adhesion to proteoglycan-rich surfaces. We therefore investigated whether controlled enzymatic degradation of surface proteoglycan molecules to a depth of about 1 microm, using chondroitinase ABC, would improve coverage by repair cells. We created superficial lesions (1.0 x 0.2 x 5 mm) in the articular cartilage of mature rabbit knees and treated the surfaces with 1 U/ml of chondroitinase ABC for four minutes. The defects were studied by histomorphometry and electron microscopy at one, three and six months. At one month, untreated lesions were covered to a mean extent of 28% by repair cells; this was enhanced to a mean of 53% after enzyme treatment. By three months, the mean coverage of both control and chondroitinase-ABC-treated defects had diminished dramatically to 0.2% and 13%, respectively, but at six months both untreated and treated lesions had a similar coverage of about 30%, not significantly different from that achieved in untreated knees at one month. These findings suggest that, with time, chondrocytes near the surface of the defect may compensate for the loss of proteoglycans produced by enzyme treatment, thereby restoring the inhibitory properties of the matrix as regards cell adhesion. This supposition was confirmed by electron microscopy. Our results have an important bearing on attempts made to induce healing responses by transplanting chondrogenic cells or by applying growth factors.

Animals↗
PubMed1991

Autogenous meniscus grafts in articular cartilage defects--an experimental study.

Many methods have been attempted to repair defects in the articular cartilage involving the subchondral bone, but no satisfactory method has yet been established. We performed an experimental study utilizing autogenous meniscus grafts for defects in the articular cartilage involving the subchondral bone. Sixty-two knees of 31 rabbits were thus treated. Gross and histological examinations were performed in animals sequentially sacrificed after 2 to 24 weeks. In gross examinations, the articular surface was smooth and the degenerative changes were slight although the grafted area appeared as a piece of whitish meniscus in all experimental knees. Histologically, 12 weeks were necessary for complete union in the superficial zone of the junction between the grafted meniscus and the subchondral bone. However, the junction in the deep zone was completely united after two weeks. Degenerative changes, such as fibrillation or ulceration were not noted on the surface of the grafted meniscus. The chondrocytes of the meniscus survived for as long as 24 weeks. The autogenous meniscus graft appears to be a promising alternative for defects in the articular cartilage.

Animals↗
PubMed2003

The effect of link peptide on proteoglycan synthesis in equine articular cartilage.

The basal rate of in vitro proteoglycan (PG) synthesis in explants of equine articular cartilage was subject to considerable variation in animals of the same age but was greater in younger than older animals. Synthesis of PGs in explant cultures was stimulated by a synthetic link peptide, identical in sequence to the N-terminus of the link protein (LP) of PG aggregates, in a similar manner to that demonstrated previously for human articular cartilage [Biochem. Soc. Trans. 25 (1997) 427; Arthritis Rheum. 41 (1998) 157]. Stimulation occurred in tissue from animals ranging from 1 to 30 years old but older animals required higher concentrations of peptide to produce a measurable response. Synthesis of PGs increased in a concentration-dependent manner and was paralleled by increases in the ability of aggrecan monomers to form aggregates with hyaluronan (HA). In addition to its effect on synthesis of PGs, link peptide also increased synthesis of both aggrecan and LP mRNA. Cartilage explant and chondrocyte cultures secreted small amounts of biologically active interleukin 1 (IL 1) and secretion of this cytokine was reduced considerably by the addition of link peptide. Reduction in the activity of this catabolic cytokine coupled with the increased synthesis of mRNA for aggrecan and link peptide may be the mechanism by which link peptide exerts its positive effect on the rate of PG synthesis in articular cartilage.

Age Factors↗
PubMed1991

Cartilage maintenance in osteoarthritis: interaction of cytokines, NSAID and prostaglandins in articular cartilage damage and repair.

The structural integrity of the matrix of human articular cartilage is maintained by a dynamic equilibrium between synthesis and degradation. In osteoarthritis (OA), synthesis may be inhibited by the presence of subnanogram quantities of the cytokine interleukin 1 (IL-1), leading in the longterm to loss of matrix and susceptibility to mechanical damage. IL-1 may also inhibit the potential for repair processes to take place in this cartilage if continued synthesis and secretion of the cytokine occurs. Evidence is presented that animal and human cartilages are sensitive to the action of certain nonsteroidal antiinflammatory drugs (NSAID) in inhibiting the synthesis of cartilage proteoglycan and also diminishing the repair activity of cartilage recovering after IL-1. In OA cartilage, the sensitivity to action of NSAID may depend on the state of the tissue in terms of glycosaminoglycan (GAG) turnover and GAG synthetic activity of the indigenous chondrocytes. Preliminary investigations of the prostaglandin analog misoprostol on the synthetic repair activities of animal and human cartilage in the presence of NSAID are reported.

Alprostadil↗