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PubMed1999

Mapping the physiological parameters of articular cartilage with magnetic resonance imaging.

The ability of magnetic resonance imaging (MRI) to visualize the spatial distribution of parameters related to the physiological and structural properties of tissues makes it an ideal tool for the study of articular cartilage. A variety of ingenious MRI methods have been devised to probe the complex composition and biochemistry of normal and degenerate articular cartilage. In this article we review the current status of this research and pose some questions concerning the future directions of articular cartilage research and clinical applications.

Cartilage Diseases↗
PubMed1990

The N-terminal sequence of the large proteoglycan of articular cartilage.

A peptide with hyaluronic acid-binding properties was isolated from trypsin digests of bovine articular cartilage proteoglycan aggregate. This peptide originated from the N-terminus of the proteoglycan core protein, retained its function of forming complexes with hyaluronate and link protein and contained at least one keratan sulfate chain. Amino acid sequence data demonstrated that the first six amino acid residues of the N-terminus of bovine articular cartilage proteoglycan core protein differed from the same region from the rat chondrosarcoma proteoglycan. Further sequence data indicate areas of considerable sequence homology in the hyaluronic acid-binding regions of proteoglycans from the two species.

Amino Acid Sequence↗
PubMed2004

Mature bovine articular cartilage contains abundant aggrecan that is C-terminally truncated at Ala719-Ala720, a site which is readily cleaved by m-calpain.

Extracts of normal mature articular cartilage contain aggrecan molecules which bear the G1 domain (the N-terminal globular domain of aggrecan) and are C-terminally truncated by proteolysis at a number of sites. A proportion of these molecules are generated by an aggrecanase and/or matrix-metalloproteinase-mediated cleavage in the IGD (interglobular domain between the G1 and G2 domains of aggrecan). However, the proteinase(s) responsible for formation of the majority of the larger G1-G2 and glycosaminoglycan-bearing truncated species is (are) unknown. N-terminal sequencing of aggrecan core fragments generated by m-calpain digestion of bovine aggrecan has identified four novel cleavage sites: one within the CS (chondroitin sulphate)-1 domain (at one or more of the bonds Ser1229-Val1230, Ser1249-Val1250, Ser1287-Val1288, Gly1307-Val1308 and Ser1346-Val1347), two within the IGD (at bonds Ala474-Ala475 and Gly365-Gly366) and one within the KS (keratan sulphate) domain (at Ala719-Ala720). A new monoclonal antibody (SK-28) to the C-terminal neoepitope at M710VTQVGPGVA719 showed that aggrecan products generated by this cleavage are present in high abundance in mature bovine articular cartilage extracts. We conclude that m-calpain, or an unidentified proteinase with the capacity to cleave at the same site, is active during aggrecan biosynthesis/secretion by mature chondrocytes or in the matrix of mature bovine articular cartilage in vivo.

Aggrecans↗
PubMed2005

Biologic approaches to articular cartilage surgery: future trends.

The treatment of unicompartmental osteoarthritis and focal chondral pathologic conditions in the knee in active aging athletes has captured the interest of patients, clinicians, basic scientists, and medical industry researchers. Most would agree that a biologic solution to treating hyaline cartilage injuries and degeneration would be optimal over prosthetic joint arthroplasty. Articular cartilage resurfacing techniques and biologic surgical methods continue to evolve and have gained more acceptance in orthopedic practice. A consensus exists for the ultimate goal of achieving a more predictable and durable result after surgical tissue repair or regeneration. Numerous promising approaches are now on the horizon and although the final word is far from in, the integration of many of the anticipated advances in molecular medicine, biomedical engineering, polymer chemistry, cell biology, and clinical orthopedics contributes to an exciting and rapidly evolving field. This article reviews the current concepts of the biologic approach to articular cartilage pathologic conditions and discusses future trends and novel technologies.

Arthroplasty↗
PubMed2006

Articular cartilage repair in the adolescent athlete: is autologous chondrocyte implantation the answer?

OBJECTIVE: To determine the evidence base for recommendations regarding autologous chondryocyte implantation in adolescent athletes. MATERIALS AND METHODS: All literature on articular cartilage repair from MEDLINE search dated 1990 to 2006 was reviewed. The majority of articles describe surgical technique and indications. Three techniques for secondary articular cartilage repair have been identified: autologous chondrocyte implantation, autologous osteochondral implants, and marrow stimulation techniques. The initial literature search identified 4 studies that reported the effectiveness and durability of autologous chondrocyte implantation in adults and 2 studies that reported the outcomes of autologous chondrocyte implantation in adolescent athletes. No results of osteochondral implantation or marrow stimulation techniques in adolescent athletes have been published. RESULTS: Acceptable repair rates with all 3 techniques have been reported in adult athletes. Two studies reported high success using autolgous chondrocyte implantation (ACI) in children. CONCLUSIONS: Articular cartilage injury in young athletes remains a difficult problem. The ideal situation is early diagnosis and primary repair, particularly with lesions of the knee, elbow, and ankle. In cases where primary repair is not possible or has been unsuccessful and the lesion is large or symptomatic, secondary repair with either marrow stimulation, microfracture, autologous chondrocyte implantation, or autologous osteochondral grafting may be used. However, at present only the results of ACI repair have been reported for adolescent athletes.

Adolescent↗
PubMedDate not supplied

[Cellular aspects of the aging of articular cartilage. I. Condylar cartilage with a normal surface sampled from normal knees].

The authors studied the cellular density of articular cartilage taken from the femoral condyles of 77 autopsy subjects at Hôpital Lariboisière in Paris. This study showed a decrease in the cellular density (number of chondrocytes per mm2) going from the superficial zone towards the calcified zone of the cartilage in all layers, as a function of the age of the subjects. The decrease in cellular density is in the order of about 50% of the total chondrocyte number when subjects younger than 40 are compared with those older than 80. The demonstration of a regular increase in the number of empty lacunae per mm2 with the age of the subjects, i.e. lacunae without chondrocytes, suggest that the cause of this decrease in cellular density of the cartilage with age could be a physiological necrosis due to "exhaustion" of the chondrocytes. The metabolic activity of the chondrocytes may also decrease with age, as suggested by the increasing proportion of alcianophobic cells, cells which are weakly or not at all labeled by radioactive sulfates which indicate the sites of biosynthesis of proteoglycans. These cellular modifications could play a role of senile fibrillation of articular cartilage and in arthrosis.

Adult↗
PubMed1995

Compartment-directed physical examination of the knee can predict articular cartilage abnormalities disclosed by needle arthroscopy.

OBJECTIVE: To determine whether physical examination maneuvers that focus on each knee compartment and assess crepitus at several distinct sites can specifically disclose articular cartilage abnormalities in the compartment being assessed. METHODS: Twenty patients with knee pain were examined before needle arthroscopy. Crepitus was sought from the patellofemoral compartment, medial tibiofemoral compartment, and lateral tibiofemoral compartment. Any crepitus felt in the distal tibia during a tibiofemoral stress maneuver was recorded as transmitted bony crepitus (TBC). Needle arthroscopy assessed articular cartilage (5 sites) and both menisci in each knee. RESULTS: Crepitus by conventional assessment revealed patellar cartilage disruption (69% sensitive, 50% specific) and abnormalities of tibiofemoral cartilage (67% sensitive, 40% specific) but could not indicate their location. Tibiofemoral crepitus found cartilage disruption in the compartment at a sensitivity of 22% and a specificity of 100%, and with added tibiofemoral stress, a sensitivity of 65% and a specificity of 94% (the one "false positive" had bare bone in the other compartment). TBC was detected in 7 compartments, all of which had focal bare bone on tibial and femoral surfaces; 6 other compartments had tibial bare bone without TBC. Thus, TBC was 54% sensitive and 100% specific for tibial bare bone, and 88% sensitive and 100% specific for bone-on-bone. CONCLUSION: Compartment-directed physical examination of the painful knee can locate and assess the severity of certain articular cartilage abnormalities that are not reliably found by conventional methods. Transmitted bony crepitus is a specific finding for bone-on-bone in the compartment being assessed.

Adult↗
PubMed1984

Morphometry of articular cartilage: a stereological method using light microscopy.

A stereological method is introduced for studying the light microscopic morphometry of articular cartilage. New parameters are presented for defining the three-dimensional structure of the articular cartilage. These include volume density of the lacunae and nuclei, numerical density of cells in 3-dimensional space, total number of cells, total volume of the lacunae in cartilage, volume and diameter of the lacuna and nucleus, the nucleus/lacuna volume ratio, and the mean volume of the matrix per cell. Using the lateral tibial condyle of the knee joint of eight rabbits, we investigated tissue preparation, sampling, morphometry, and the conditions necessary for validity and precision of the estimators. The method proved easy to use, and the estimators were precise.

Animals↗
PubMed2000

Frictional behaviour of bovine articular cartilage.

The experimentally measured indentation displacement and friction of normal and degraded (treated with chondroitinase AC) bovine articular cartilage plugs against a smooth steel plate were compared with the predictions based on the biphasic theory using the finite element method. It was found that the measured indentation displacement of both cartilage specimens could be predicted from the biphasic theory and the permeability for the degraded cartilage specimen was increased approximately three times. However, the measured friction coefficient was much lower for short period of loading, and the difference in the finite element prediction of friction coefficient between the normal and degraded cartilage specimens was not observed in the experiment. Therefore, it was concluded that both biphasic and other mechanisms were important in controlling the frictional and lubricating characteristics of articular cartilage in mixed and boundary lubrication regimes.

Animals↗
PubMedDate not supplied

Aspects of immunopathogenesis of rheumatoid arthritis correlated with some immunological parameters in histopathological and electronmicroscopical investigations of the articular cartilage.

The histopathological (H. E., V. G., PAS-Alcian, Safranine 0, Gömöri) and electron-microscopical investigations were carried out on twenty samples of articular cartilage taken during operations from patients with Rheumatoid Arthritis (R. A.) and from others with traumatism, as controls. Histopathologically, the rheumatoid synovial membrane is characterized by synovitis with abundant perivascular lymphoplasmocytic infiltrates. At the pannus synovia-cartilage junction we found the invasive and destructive inflammatory infiltrates penetrating and eroding the cartilage. The histopathological characteristics of the rheumatoid articular cartilage lie in alteration of tinctorial activity, affection of reticuline collagen network and the presence of superficial and deep cartilaginous fissures. The histopathological alterations were confirmed ultrastructurally. Immunologically we found pathological serum values regarding the immune circulating complexes (I. C. C.) (mean = 104 +/- 1.04 U), anticollagen II antibodies (mean = 538 +/- 5 U), reactive Protein C (mean = 16.75 +/- 1.95 mg%) and orosomucoid (mean = 151.1 +/- 4.91 mg%), in seropositive R. A. The corroboration of histopathological, electronmicroscopical and immunological data show the inflammatory and autoimmune feature of this rheumatic disease.

Arthritis, Rheumatoid↗
PubMed2002

The effect of estrogens and dietary calcium deficiency on the extracellular matrix of articular cartilage in Göttingen miniature pigs.

Clinical observations have suggested that estrogens are involved in the pathogenesis of postmenopausal osteoarthritis (OA). However, positive and negative associations between the incidence of OA and serum estrogen concentrations have been reported. In contrast to this, osteoporosis is regarded as a disease with a strong estrogen-dependent component. Moreover, there is an interaction between estrogen and calcium deficiency: calcium supplementation potentiates the effect of estrogen therapy. The present study was designed to investigate how estrogen deficiency affects the articular cartilage depending on calcium supply. The distribution of different types of glycosaminoglycans and collagens can be used as an indicator for extracellular matrix changes induced by estrogen deficiency. Different levels of dietary calcium were therefore fed to intact and ovariectomized Göttingen miniature pigs for one year before articular cartilage was harvested. The histochemical staining for heavy sulfated glycosaminoglycans in the extracellular matrix of ovariectomized miniature pigs, especially of those fed with a low calcium diet, was stronger in comparison to intact animals. In intact animals type II-collagen was immunodetected in all zones of unmineralized and mineralized articular cartilage, while immunostaining for this protein was negative to weak in the deep radiated fiber zone of ovariectomized minipigs. These results suggest that the synthesis of heavy sulfated glycosaminoglycans and immunohistochemically detectable type II-collagen is possibly influenced by estrogen deficiency. In conclusion, under estrogen deficiency, the extracellular matrix of articular cartilage underwent similar changes to those observed in physiologically aging cartilage where keratan sulfate is increased as a heavy sulfated glycosaminoglycan.

Animals↗
PubMed1998

Investigation into the effects of proteins and lipids on the frictional properties of articular cartilage.

The aim of this study was to investigate the effects of the proteins and the lipids on the frictional properties of articular cartilage in the mixed and boundary lubricating regimes. Bovine articular cartilage that had been treated to remove the lipids, and cartilage that had been treated to remove the proteins, from the surface layer were studied in order to investigate differences in their lubricating abilities. Tests were carried out on a sliding friction rig under contact pressures of 0.5 and 4 MPa. The results of the friction tests carried out under the 4 MPa contact pressure showed a slight increase in friction coefficient for both the lipid and the protein deficient cartilage when compared with the control cartilage. These differences were more apparent at the shorter loading times but none of the differences were found to be statistically significant. The tests at the lower contact pressure of 0.5 MPa showed that removing the lipids by washing the surface with detergent increased the friction coefficient at the shorter loading times but had no effect at the longer loading times. Digesting the cartilage with trypsin to remove the proteins from the surface layer had no effect on the friction coefficient at the shorter loading times but reduced the friction coefficient at the longer loading times. Both these results were confirmed with specimens that had both the lipids and the proteins removed from the surface layer.

Animals↗
PubMed2001

Cross-sectional comparison of synovial fluid biochemical markers in equine osteoarthritis and the correlation of these markers with articular cartilage damage.

OBJECTIVE: To investigate the relationship between biochemical markers in the synovial fluid of osteoarthritic and contralateral equine joints and gross articular cartilage pathology. DESIGN: Twenty-two horses underwent bilateral arthroscopy of their carpal or metacarpophalangeal joints following recent onset lameness. The degree of cartilage damage in each joint was scored and synovial fluid, from both the clinically affected and the contralateral joint, was collected. Bone specific alkaline phosphatase (BAP), 5D4 epitope of keratan sulphate (KS), total glycosaminoglycans (GAG) and hyaluronan (HA) were measured. RESULTS: The mean age of the horses was 4.1 years and the maximum duration of lameness was three months. Joints examined were midcarpal, antebrachiocarpal and metacarpophalangeal. The median concentration (semi-interquartile range) of BAP was significantly higher in the clinically active joint than in the contralateral joint, 21.75 (6.22) vs. 12.35 (4.07) units, while the other biomarkers measured were significantly lower in the clinically active joint than in the contralateral joint, i.e. KS 8.79 (1.96) microg/ml vs. 16.39 (5.65) microg/ml, KS:GAG ratio 0.19 (0.04) vs. 0.31 (0.10) and HA 741.6 (222) microg/ml vs. 1061.75 (325) microg/ml. BAP was positively (R=0.57), and KS (R=-0.57) and KS:GAG ratio (R=-0.49) were negatively correlated to the degree of cartilage damage within the joint. CONCLUSION: The correlation between articular cartilage damage and synovial fluid BAP and KS imparts validity to their potential use as non-invasive diagnostic aids in equine osteoarthritis (OA). The positive correlation between BAP and cartilage damage suggests that there is a link between bone turnover and cartilage damage in OA.

Alkaline Phosphatase↗
PubMed2005

A numerical method for the continuous spectrum biphasic poroviscoelastic model of articular cartilage.

A method for numerical solution of the continuous spectrum linear biphasic poroviscoelastic (BPVE) model of articular cartilage is presented. The method is based on an alternate formulation of the continuous spectrum stress-strain law that is implemented using Gaussian quadrature integration combined with quadratic interpolation of the strain history. For N time steps, the cost of the method is O(N). The method is applied to a finite difference solution of the one-dimensional confined compression BPVE stress-relaxation problem. For a range of relaxation times that are representative of articular cartilage, accuracy of the method is demonstrated by direct comparison to a theoretical Laplace transform solution.

Animals↗
PubMed1998

Spontaneous repair of superficial defects in articular cartilage in a fetal lamb model.

A fetal lamb model was developed to investigate the capacity of fetal articular cartilage for repair after the creation of a superficial defect. Superficial defects, 100 micrometers deep, were made in the articular cartilage of the trochlear groove in the distal aspect of the femur in eighteen fetal lambs that were halfway through the 145-day gestational period; the contralateral limb was used as a sham control. The wounds were allowed to heal in utero for three, seven, fourteen, twenty-one, or twenty-eight days. Seven days after the injury, the defects were filled with a hypocellular matrix, which stained lightly with safranin O. At twenty-eight days, the staining of the matrix was similar to that of the sham controls and the chondrocyte density and the architectural arrangement of the cell layers had been restored. An inflammatory response was not elicited, and no fibrous scar tissue was observed.

Animals↗
PubMed2004

Differences in the topographical distribution of articular cartilage degeneration between equine metacarpo- and metatarsophalangeal joints.

REASONS FOR PERFORMING STUDY: The equine metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints, although having virtually the same geometrical appearance, differ in the prevalence of joint pathologies, such as osteochondral fragmentation, and in biomechanical behaviour. The recently developed cartilage degeneration index (CDI) technique offers a possibility to assess quantitatively differences in cartilage degeneration between these joints and to compare these with known differences in biomechanics and clinical observations. OBJECTIVES: To compare the topographical distribution of articular cartilage degeneration across the proximal articular surface of the proximal phalanx (P1) in the equine fore- and hindlimb. METHODS: In 24 distal hindlimbs from 24 horses, articular cartilage degeneration of the proximal articular surface of P1 was quantified using the CDI. Overall CDI value (CDI(P1)) and CDI values of 6 areas of interest were determined: the medial dorsal surface (mds), lateral dorsal surface (lds), medial central fovea (mcf), lateral central fovea (lcf), medial plantar surface (mps) and lateral plantar surface (lps). The joints were divided into 4 equally sized groups of increasing CDI(P1) values. From an existing CDI database of MCP joints, 24 joints were selected with matching CDI(P1) values to the MTP joints and CDI values for the same areas of interest were determined. RESULTS: In both the MCP and MTP joints, highest CDI values were determined at the dorsal articular surfaces. Values were not significantly different between fore- and hindlimbs. In contrast to the MCP joint, CDI values at the plantar joint margin were significantly higher compared to CDI values in the central sites in the MTP joint. CDI values for the plantar surfaces of P1 were significantly higher than those for the palmar surfaces in the forelimb in joints with advanced stages of OA; and values for the central regions of P1 were significantly lower in the hindlimb compared with the forelimb in joints with severe OA. CONCLUSIONS: In both fore- and hindlimbs, initial cartilage degeneration started at the dorsal articular margin of P1. There was a major difference in the spread of cartilage degeneration; in the forelimb both the central and palmar parts are about equally involved, whereas in the hindlimb the plantar parts were significantly more and the central parts significantly less involved. These differences can be linked to differences in biomechanical loading reported elsewhere. POTENTIAL RELEVANCE: This study supports the hypothesis that differences in biokinematics between fore- and hindlimbs are associated with differences in the development of cartilage degeneration and other joint pathologies such as osteochondral fragmentation in the MCP and MTP joints. This information is indispensable for a better understanding of the dynamic nature and progression of these joint disorders and may be of help when monitoring the effects of therapeutic interventions and preventative measures.

Animals↗