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PubMed2006

Topographical variation in glycosaminoglycan content in human articular cartilage.

The weight-bearing status of articular cartilage has been shown to affect its biochemical composition. We have investigated the topographical variation of sulphated glycosaminoglycan (GAG) relative to the DNA content of the chondrocyte in human distal femoral articular cartilage. Paired specimens of distal femoral articular cartilage, from weight-bearing and non-weight-bearing regions, were obtained from 13 patients undergoing above-knee amputation. After papain enzyme digestion, spectrophotometric GAG and fluorometric DNA assays assessed the biochemical composition of the samples. The results were analysed using a paired t-test. Although there were no significant differences in cell density between the regions, the weight-bearing areas showed a significantly higher concentration of GAG relative to DNA when compared with non-weight-bearing areas (p = 0.02). We conclude that chondrocytes are sensitive to their mechanical environment, and that local loading conditions influence the metabolism of the cells and hence the biochemical structure of the tissue.

Adolescent↗

PubMed1999

Development and aging of the articular cartilage of the rabbit knee joint: Distribution of biglycan, decorin, and matrilin-1.

We determined the distributions of the small proteoglycans biglycan and decorin and the glycoprotein matrilin-1 (cartilage matrix protein) during development and aging of articular cartilage in the rabbit knee joint. Before cavitation, the matrices of the interzone and the adjacent epiphyseal cartilage do not contain biglycan or decorin, but some chondrocytes express their mRNAs. Matrilin-1 is found only in the deeper epiphyseal cartilage. After cavitation, biglycan and decorin are detected in the presumptive articular cartilage, but there is no matrilin-1. All are present in the underlying epiphyseal cartilage. In the neonate, the epiphyseal cartilage is ossified and the articular cartilage becomes a discrete layer. Biglycan and decorin accumulate in the articular cartilage, but matrilin-1 remains confined to the residual epiphyseal cartilage. In the adult, the distributions of biglycan and decorin are highly variable. Decorin tends to be confined to the central region; matrilin-1 is absent. The findings indicate that the articular and epiphyseal cartilages are different from the earliest developmental stages. The epiphyseal cartilage can be identified by its possession of matrilin-1. Epiphyseal cartilage is removed during development to leave the articular cartilage. The relationships between the distributions of decorin and matrilin-1 and the fibrillar collagens are discussed. (J Histochem Cytochem 47:1603-1615, 1999)

Aging↗

PubMed2001

Magnetic resonance imaging of articular cartilage.

Magnetic resonance imaging is the optimal modality for assessing articular cartilage because of superior soft tissue contrast, direct visualization of articular cartilage, and multiplanar capability. Despite these advantages, there has been disagreement as to the efficacy of magnetic resonance imaging of articular cartilage. The reason for this controversy is multifactorial but in part is attributable to the lack of the use of optimized pulse sequences for articular cartilage. The current authors will review the current state of the art of magnetic resonance imaging of articular cartilage and cartilage repair procedures, discuss future new directions in imaging strategies and methods being developed to measure cartilage thickness and volume measurements, and propose a magnetic resonance imaging protocol to evaluate cartilage that is achievable on most magnetic resonance scanners, vendor independent, practical (time and cost efficient), and accepted and used by a majority of musculoskeletal radiologists.

Arthrography↗

PubMed2000

Magnetic resonance imaging of articular cartilage and evaluation of cartilage disease.

Clinical magnetic resonance imaging of articular cartilage is possible by using techniques that offer high contrast between articular cartilage and adjacent structures in reasonable examination times. The fat-suppressed, three-dimensional, spoiled gradient-echo sequence has been reported to be accurate and reliable, and the addition of this sequence to a routine examination does not significantly compromise patient throughput. Fast spin-echo imaging also shows promise in the clinical evaluation of articular cartilage, because the newer, stronger-gradient systems allow thinner slice acquisition with two-dimensional sequences. Together, these sequences allow the evaluation of intrachondral lesions and surface defects. Furthermore, quantitative measurements of cartilage volume for follow-up studies are possible with the use of the fat-suppressed, three-dimensional, spoiled gradient-echo sequence.

Cartilage Diseases↗

PubMed2002

Surface fissures in articular cartilage: new concepts, hypotheses and modeling.

OBJECTIVE: Clarification and mesomechanical modeling of the inception of fissures at the surface of articular cartilage. DESIGN: Articular cartilage is described as a macroscopically heterogeneous medium consisting of zones - layers - with different orientation of collagen fibers. BACKGROUND: Degradation of mechanical properties of cartilage is a serious, still not fully clarified problem that deserves attention. METHODS: Theoretical analysis based on a survey of known experimental findings related to the subject. The general author's mesomechanical concept of modeling heterogeneous media is applied to the elucidation and description of the formation of fissures at the surface of articular cartilage. RESULTS: Our model clarifies how the high tensile stresses in the collagen fibers of the superficial tangential zone depend on the rate of loading. CONCLUSIONS: The superficial cracks are caused predominantly by a very quick loading. This explains among others the high incidence of post-traumatic osteoarthritis of the lower extremity after accidents and injuries in sports. RELEVANCE: Superficial fissures in articular cartilage are observed in joints with primary osteoarthritis. The current study specifies the kinds of loading that lead to their inception.

Biomechanical Phenomena↗

PubMed2000

MR imaging of articular cartilage.

With the advent of new treatments for articular cartilage disorders, accurate noninvasive assessment of articular cartilage, particularly with MR imaging, has become important. Understanding the MR imaging features of articular cartilage has led to the development of two types of routinely available MR imaging techniques which have demonstrated clinical accuracy and interobserver reliability.

Artifacts↗

PubMed1991

[The distribution of S-100 protein positive chondrocytes in the human articular cartilages under aging or diseased conditions].

There have been few reports on the localization of S-100 protein positive chondrocytes in the human articular cartilages. We studied 59 articular cartilages of the aged subjects, 65 osteoarthritic (OA) and 39 rheumatoid arthritic (RA) articular cartilages, to detect the histological localization of S-100 protein using immunoperoxidase method (ABC). The results obtained from normal cartilages demonstrated strongly positive cells representing hypertrophic chondrocytes in the perivascular areas of the neonatal articular cartilage and in the deep zone of the infant articular cartilage. The moderately positive cells were found in the intermediate zone of infant and adult articular cartilages. In mild OA, there were many positive chondrocytes in the intermediate zone with erosion of the surface layer, while in moderate or severe OA many strongly positive cells were found in clusters. The hypertrophic cells in the metaplastic cartilage arising from bone marrow in subjects with severe OA, or from pannus after RA were also positive. It is therefore, suggested that S-100 protein may be correlated with the metabolic activity of the cartilage matrix such as collagen and proteoglycan, as reported in the literature. S-100 protein further, appears to be useful for evaluating histologically the activity of cartilage repair in the pathologic human articular cartilages.

Adolescent↗

PubMed1999

Biomechanical analysis of a chondrocyte-based repair model of articular cartilage.

The objective of this study was to evaluate the biomechanical properties of newly formed cartilaginous tissue synthesized from isolated chondrocytes. Cartilage from articular joints of lambs was either digested in collagenase to isolated chondrocytes or cut into discs that were devitalized by multiple freeze-thaw cycles. Isolated cells were incubated in suspension culture in the presence of devitalized cartilage matrix for 3 weeks. Multiple chondrocyte/matrix constructs were assembled with fibrin glue and implanted subcutaneously in nude mice for up to 6 weeks. Testing methods were devised to quantify integration of cartilage pieces and mechanical properties of constructs. These studies showed monotonic increase with time in tensile strength, fracture strain, fracture energy, and tensile modulus to values 5-10% of normal articular cartilage by 6 weeks in vivo. Histological analysis indicated that chondrocytes grown on dead cartilage matrix produced new matrix that integrated individual cartilage pieces with mechanically functional tissue.

Animals↗

PubMed2006

Cellular and molecular mechanisms of synovial joint and articular cartilage formation.

Synovial joints and articular cartilage play crucial roles in the skeletal function, but relatively little is actually known about their embryonic development. Here we first focused on the interzone, a thin mesenchymal cell layer forming at future joint sites that is widely thought to be critical for joint and articular cartilage development. To determine interzone cell origin and fate, we microinjected the vital fluorescent dye DiI at several peri-joint sites in chick limbs and monitored the behavior and fate of labeled cells over time. Peri-joint mesenchymal cells located immediately adjacent to incipient joints migrated, became part of the interzone, and were eventually found in epiphyseal articular layer and joint capsule. Interzone cells isolated and reared in vitro expressed typical phenotypic markers, including GDF-5, Wnt-14, and CD-44, and differentiated into chondrocytes over time. To determine the molecular mechanisms of articular chondrocyte formation, we carried out additional studies on the ets transcription factor family member ERG and its alternatively spliced variant C-1-1 that we previously found to be expressed in developing avian articular chondrocytes. We cloned the human counterpart of avian C-1-1 (ERGp55Delta81) and conditionally expressed it in transgenic mice under cartilage-specific Col2 gene promotor-enhancer control. The entire transgenic mouse limb chondrocyte population exhibited an immature articular-like phenotype and a virtual lack of growth plate formation and chondrocyte maturation compared to wild-type littermate. Together, our studies reveal that peri-joint mesenchymal cells take part in interzone and articular layer formation, interzone cells can differentiate into chondrocytes, and acquisition of a permanent articular chondrocyte phenotype is aided and perhaps dictated by ets transcription factor ERG.

Animals↗

PubMed2006

The structural architecture of adult mammalian articular cartilage evolves by a synchronized process of tissue resorption and neoformation during postnatal development.

OBJECTIVE: During postnatal development, mammalian articular cartilage acts as a surface growth plate for the underlying epiphyseal bone. Concomitantly, it undergoes a fundamental process of structural reorganization from an immature isotropic to a mature (adult) anisotropic architecture. However, the mechanism underlying this structural transformation is unknown. It could involve either an internal remodelling process, or complete resorption followed by tissue neoformation. The aim of this study was to establish which of these two alternative tissue reorganization mechanisms is physiologically operative. We also wished to pinpoint the articular cartilage source of the stem cells for clonal expansion and the zonal location of the chondrocyte pool with high proliferative activity. METHODS: The New Zealand white rabbit served as our animal model. The analysis was confined to the high-weight-bearing (central) areas of the medial and lateral femoral condyles. After birth, the articular cartilage layer was evaluated morphologically at monthly intervals from the first to the eighth postnatal month, when this species attains skeletal maturity. The overall height of the articular cartilage layer at each juncture was measured. The growth performance of the articular cartilage layer was assessed by calcein labelling, which permitted an estimation of the daily growth rate of the epiphyseal bone and its monthly length-gain. The slowly proliferating stem-cell pool was identified immunohistochemically (after labelling with bromodeoxyuridine), and the rapidly proliferating chondrocyte population by autoradiography (after labelling with (3)H-thymidine). RESULTS: The growth activity of the articular cartilage layer was highest 1 month after birth. It declined precipitously between the first and third months, and ceased between the third and fourth months, when the animal enters puberty. The structural maturation of the articular cartilage layer followed a corresponding temporal trend. During the first 3 months, when the articular cartilage layer is undergoing structural reorganization, the net length-gain in the epiphyseal bone exceeded the height of the articular cartilage layer. This finding indicates that the postnatal reorganization of articular cartilage from an immature isotropic to a mature anisotropic structure is not achieved by a process of internal remodelling, but by the resorption and neoformation of all zones except the most superficial (stem-cell) one. The superficial zone was found to consist of slowly dividing stem cells with bidirectional mitotic activity. In the horizontal direction, this zone furnishes new stem cells that replenish the pool and effect a lateral expansion of the articular cartilage layer. In the vertical direction, the superficial zone supplies the rapidly dividing, transit-amplifying daughter-cell pool that feeds the transitional and upper radial zones during the postnatal growth phase of the articular cartilage layer. CONCLUSIONS: During postnatal development, mammalian articular cartilage fulfils a dual function, viz., it acts not only as an articulating layer but also as a surface growth plate. In the lapine model, this growth activity ceases at puberty (3-4 months of age), whereas that of the true (metaphyseal) growth plate continues until the time of skeletal maturity (8 months). Hence, the two structures are regulated independently. The structural maturation of the articular cartilage layer coincides temporally with the cessation of its growth activity--for the radial expansion and remodelling of the epiphyseal bone--and with sexual maturation. That articular cartilage is physiologically reorganized by a process of tissue resorption and neoformation, rather than by one of internal remodelling, has important implications for the functional engineering and repair of articular cartilage tissue.

Adult↗

PubMed1985

Effect of electrocautery on fresh human articular cartilage.

The use of high energy devices has been suggested for intra-articular surgery. Experimental studies have been performed using the laser and electrocautery. However, clinical application has primarily been with the use of the electrocautery. Electrosurgery is currently being used for lateral retinacular release as well as meniscal surgery. Inadvertent damage to articular cartilage may occur, especially during meniscal resection. The objective of the current study is to assess the effect of the Concept electrocautery with the meniscal cutting electrode on fresh human articular cartilage. Twenty fresh tibial plateaus removed at the time of total knee arthroplasty were subjected to electrocautery currents ranging from 25 to 82.5 W. The articular cartilage was stained with hematoxylin and eosin. The extent of cartilage necrosis was quantitated as a percentage of the thickness of the articular cartilage. A dose response curve was developed. The extent of articular cartilage necrosis with the electrocautery setting of 20 (24.4 W) commonly used for meniscal resection resulted in only an 11.4%-injury to the articular cartilage. At the manufacturer's recommended setting of 24 (27 W), a 16% depth of laceration of the articular cartilage may be anticipated. We conclude that the lowest current setting possible should be utilized for meniscal surgery and the risk of articular cartilage damage from inadvertent injury is not excessive.

Cartilage, Articular↗

PubMed2001

An in situ calibration of an ultrasound transducer: a potential application for an ultrasonic indentation test of articular cartilage.

A change in mechanical properties of articular cartilage would be considered one of the most reliable signs of cartilage degeneration. While an indentation method has the potential to measure the cartilage properties in vivo, an accurate measurement of cartilage thickness in situ is technically difficult. An ultrasound transducer has often been used to measure the cartilage thickness. However, its accuracy is limited by the lack of an accurate measurement of the ultrasound speed of cartilage, for the ultrasound speed varies according to the pathological conditions of the tissue. Therefore, the objective of this study is to develop an in situ calibration method of predicting the true ultrasound speed of cartilage and thus allow the ultrasound transducer to measure the thickness of the tissue with great accuracy. By simultaneously implementing an indentation testing protocol using the ultrasound transducer as an indenter, this method can also provide an indentation stiffness measurement of cartilage. The feasibility of the proposed method was examined using normal and proteoglycan-depleted cartilage specimens. It was found that the true ultrasound speed measured by the in situ calibration method was sensitive to the proteoglycan depletion (1735+/-35 m/s for normal, and 1598+/-28 m/s for proteoglycan-depleted cartilage), and that the measured cartilage thickness was consistently accurate regardless of the tissue condition. The measured indentation stiffness of articular cartilage was also sensitive to the tissue condition. Thus, this study demonstrates that the proposed ultrasonic indentation technique can be used to accurately identify the abnormality of articular cartilage in situ.

Animals↗

PubMed1995

Magnesium whitlockite deposition in articular cartilage: a study of 80 specimens from 70 patients.

OBJECTIVE: To examine articular cartilage from a number of joint sites, using a large sample group, for the presence of magnesium whitlockite crystal deposition. METHODS: Articular cartilage specimens were taken from a total of 70 patients. The majority of specimens were taken from femoral heads, with smaller numbers from femoral condyle, tibial plateau, radius, ulna, and several small peripheral joints. Normal and osteoarthritic articular cartilage specimens were obtained from patients undergoing prosthesis replacement or amputation. Specimens were resin embedded and examined using transmission electron microscopy and x ray microanalysis. RESULTS: Magnesium whitlockite crystals were identified, on the basis of morphology, size and elemental composition, in articular cartilage from all sites sampled. The distribution of crystals was similar in all samples (restricted to the superficial zone), although the density of deposition was extremely variable, with the greatest density observed in femoral head specimens. No magnesium whitlockite crystals were observed in osteophytic or epiphysial cartilage. CONCLUSIONS: This study demonstrated the widespread extent of magnesium whitlockite deposition in human articular cartilage, albeit at much lower density than previously reported in femoral head articular cartilage. In consideration of possible roles for these crystals in articular cartilage, it is concluded that an opportunistic mode of formation, possibly influenced by mechanical stresses, would be most plausible.

Adolescent↗

PubMed1996

Transmission of rapidly applied loads through articular cartilage. Part 2: Cracked cartilage.

A model of articular cartilage suffering rapidly applied loads and containing splits and fissures is presented. The possibility of cracks propagating through the cartilage collagen network is analysed using elastic fracture mechanics. Cracks are modelled using the distributed dislocation technique and the crack tip stress intensity factors are thereby evaluated. The mode I (tensile) stress intensity factors are generally much larger than the mode II (shearing) factors for cracks at the articular surface and close to, and at oblique angles to, the cartilage-bone interface, two regions where cartilage cracks have been observed. This suggests an opening, tensile mode of failure. The mode II factors are larger for cracks running along the interface. The rapidly loaded cracked cartilage model may explain the splits observed in osteoarthrotic cartilage.

Biomechanical Phenomena↗

PubMed1991

[Experimental study on histological changes of articular cartilage of femoral head under nonweight-bearing conditions].

Histological changes of articular cartilage of the femoral head in the nonweight-bearing conditions were investigated using 10-week-old Wistar rats whose hind limbs had been unilaterally transected. At 2 weeks after limb transection, decreased DNA synthesis in chondrocytes and depletion of glycosaminoglycan in the cartilage matrix in the intermediate zone of the articular cartilage were observed. After 8 weeks, articular cartilage thickness decreased significantly, and at 16 weeks the number of chondrocytes diminished in comparison with those of a weight-bearing femoral head. At 20 weeks, chondrocyte death and reduced width of articular cartilage became evident. No osteoarthritic changes, however, were observed under nonweight-bearing conditions. These findings suggest that weight-bearing is very important in maintaining of both the structure and metabolism of the articular cartilage.

Animals↗

PubMed1997

[Lesions of articular cartilage and their treatment].

Lesions of human articular cartilage most often are the result of a pathogenetically unclear disease process eventually leading to primary osteoarthrosis. The increasing incidence of traumatic injuries during sport activities, leading to lesions of cartilage and bone, is also worth noting. In addition, osteochondrosis dissecans and hereditary dysplasias of the skeletal system may lead to osseous and cartilaginous lesions. Adult articular cartilage has only very limited repair capacity in response to acute and chronic insults. Even now, diagnostic tools and methods of diagnosing cartilaginous lesions are still far from accurate. Lesions seen by conventional imaging technology chiefly represent late and irreversible damage of joint cartilage structures. The present review first summarizes current basic knowledge of joint anatomy and physiology, to enable the reader to understand better the unique nature of cartilaginous lesions and the difficulties and controversies involved in old and novel experimental methodologies in cartilage repair. It then critically evaluates developments in orthopedic therapy for repair of articular cartilage lesions.

Adult↗

PubMed1996

Presence of pro-forms of decorin and biglycan in human articular cartilage.

The proteoglycans decorin and biglycan in extracts of human articular cartilage were analysed by SDS/PAGE and immunoblotting, using antisera raised to peptide sequences present in the pro-regions and the mature core proteins. In adult cartilage, both pro-forms and mature processed forms of the proteoglycan core protein were observed for both decorin and biglycan. In the case of biglycan, it was also shown that additional proteolytic processing takes place after removal of the propeptide and that this accounts for the presence of non-glycanated forms of the molecule. For both decorin and biglycan, the relative abundance of the pro-forms was much less in the juvenile than the adult. Different adult connective tissues, including meniscus, tendon and intervertebral disc were also examined for the presence of pro-forms of the proteoglycans. While the mature form of decorin was present at a similar level in extracts of all tissues examined, the pro-form was only detected in the articular cartilage. In the case of biglycan, the abundance of the mature form was more varied, with high levels in articular cartilage, intermediate levels in meniscus and the annulus fibrosus of the intervertebral disc, low levels in the nucleus pulposus of the intervertebral disc, and non-detectable levels in the patellar tendon. The pro-form of biglycan was detected in the disc tissue extracts, albeit at a lower level than in articular cartilage, but was not detected in the meniscus or tendon. The proportion of the pro-form relative to the mature form of biglycan was, however, higher in the nucleus pulposus of the intervertebral disc than in articular cartilage. Thus, the persistence of pro-forms of both decorin and biglycan is a feature of the extracellular matrix of some connective tissues, although their abundance is both tissue- and age-dependent, with adult articular cartilage being a particularly rich source.

Adult↗

PubMed1995

Comparison of optical, needle probe and ultrasonic techniques for the measurement of articular cartilage thickness.

Analysis of the mechanical properties of articular cartilage necessitates determination of thickness of the tested tissue. To evaluate the suitability of different methods for thickness measurements, the thickness of bovine and canine knee articular cartilage was determined with optical (stereomicroscopic), needle probe and ultrasonic techniques. The results obtained with the stereomicroscope and the needle probe showed high, linear correlations (r = 0.97, n = 80). The mean thickness obtained with the needle was slightly higher than the optical thickness (0.88 +/- 0.36 mm vs 0.85 +/- 0.34 mm, mean +/- S.D., n = 80, p < 0.01, matched-pairs Student t-test) or the ultrasonic thickness (0.93 +/- 0.42 mm vs 0.87 +/- 0.36 mm, n = 45, p < 0.05). The high scatter between optical and ultrasonic thickness, considered to be due to complex measurement geometry of canine knee articular cartilage, invalidated the use of the A-mode, 10 MHz-ultrasonic device for thickness measurements. Based on the results of uncertainty analysis it is concluded that optical and needle probe methods can be used interchangeably when determining shear modulus of articular cartilage with indentation tests. However, if high area-aspect ratios (indenter radius-to-cartilage thickness ratios) are used in the indentation measurements uncertainty in shear modulus may be markedly increased due to possible errors in the measurement of cartilage thickness.

Animals↗