Variations among joints in the initiation and progression of degeneration may be explained, in part, by metabolic, biochemical and biomechanical differences. Compared to the cartilage in the knee ...joint, ankle cartilage has a higher content of proteoglycans and water, as well as an increased rate of proteoglycan turnover and synthesis, all of which are responsible for its increased stiffness and reduced permeability. Chondrocytes within ankle cartilage have a decreased response to catabolic factors such as interleukin-1 and fibronectin fragments, compared to the chondrocytes of knee cartilage. Moreover, in response to damage, ankle chondrocytes synthesize proteoglycans at a higher rate than that found in knee cartilage chondrocytes, which suggests a greater capacity for repair. In addition to the cartilages of the two joints, the underlying bones also respond differently to degenerative changes. Taken together, these metabolic, biochemical and biomechanical differences may provide protection to the ankle.
Cartilage was obtained from eight matched knee (tibiofemoral and femoropatellar) and ankle (talocrural) joints of five different donors (both left and right from donors 14, 22, and 38 years of age, ...and left only from donors 31 and 45 years of age) within 24 hours of death. All cartilage was graded as normal by the macroscopic visual Collins' scale and the histological Mankin scale. Cylindrical disks of cartilage were harvested from 10 sites within the tibiofemoral and femoropatellar joint surfaces and four sites within the talocrural joint, and uniaxial confined compression measurements were performed to quantify a spectrum of physical properties including the equilibrium modulus, hydraulic permeability, dynamic stiffness, streaming potential, electrokinetic coupling coefficient, and electrical conductivity. Matched specimens from the same 14 sites were used for complementary measurements of biochemical composition and molecular interaction, including water content, hypotonic swelling behavior, and sulfated glycosaminoglycan and collagen contents. In comparison of the top 1-mm slices of talar cartilage with the top 1-mm of tibiofemoral cartilage, the talar cartilage appeared denser with a higher sulfated glycosaminoglycan content, lower water content, higher equilibrium modulus and dynamic stiffness, and lower hydraulic permeability. The equilibrium modulus increased with increasing sulfated glycosaminoglycans per wet weight and decreased with increasing water content for all joint surfaces. Multiple linear regression showed that greater than 80% of the variation in the equilibrium modulus could be accounted for by variations in the biochemical parameters (water content, sulfated glycosaminoglycans/wet weight, and hydroxyproline content/wet weight) for each joint surface. Nonhomogeneous depth-dependent changes in the physical properties and biochemical composition of full-thickness distal femoral cartilage were consistent with previous reports. Since the compressive deformation of cartilage during cyclic loading is confined to the more superficial regions, the differences in properties of the upper regions of the talar compared with tibiofemoral or femoropatellar cartilage may be important in the etiology of osteoarthritis.
Objective To introduce a novel X-ray technology, diffraction-enhanced X-ray imaging (DEI), in its early stages of development, for the imaging of articular cartilage.
DesignDisarticulated and/or ...intact human knee and talocrural joints displaying both undegenerated and degenerated articular cartilage were imaged with DEI. A series of three silicon crystals were used to produce a highly collimated monochromatic X-ray beam to achieve scatter-rejection at the microradian level. The third crystal (analyser) was set at different angles resulting in images displaying different characteristics. Once the diffraction enhanced (DE) images were obtained, they were compared to gross and histological examination.
Results Articular cartilage in both disarticulated and intact joints could be visualized through DEI. For each specimen, DE images were reflective of their gross and histological appearance. For each different angle of the analyser crystal, there was a slight difference in appearance in the specimen image, with certain characteristics changing in their contrast intensity as the analyser angle changed.
ConclusionsDEI is capable of imaging articular cartilage in disarticulated, as well as in intact joints. Gross cartilage defects, even at early stages of development, can be visualized due to a combination of high spatial resolution and detection of X-ray refraction, extinction and absorption patterns. Furthermore, DE images displaying contrast heterogeneities indicative of cartilage degeneration correspond to the degeneration detected by gross and histological examination.
We have previously described a large proteoglycan named superficial zone protein that was isolated and purified from culture medium of superficial slices of bovine articular cartilage. Monoclonal ...antibodies were raised against superficial zone protein and used as probes in Western blot analyses for immunohistochemical studies both to determine precisely which cells within the joint synthesize the proteoglycan and to isolate a cDNA fragment from a bovine chondrocyte lambdagt11 library that encodes part of the proteoglycan. The cDNA fragment that was obtained with use of monoclonal antibody 6-A-1 encodes the 3' end of the sequence for superficial zone protein. On Western blots, monoclonal antibody 3-A-4 recognized an epitope on native, but not reduced, superficial zone protein, whereas monoclonal antibody 6-A-1 reacted with both native and denatured antigen. The proteoglycan was immunolocalized with monoclonal antibody 3-A-4 in chondrocytes predominantly within the superficial zone of fetal and adult articular cartilage and in some cells of the synovial lining. However, the proteoglycan was not detected in chondrocytes deep in articular cartilage, in nasal septal cartilage, or in synovial stromal cells. The only matrix staining positively for superficial zone protein was at the articular surface bordering the synovial cavity in adult, but not fetal, joints. Isolated chondrocytes and synovial cells showed intracellular binding of monoclonal antibody 3-A-4, and flow-cytometric analysis with the antibody gave the following percentages of immunopositive cells: 37.4, 52.5, 3.4, and 7.5 from chondrocytes from the full-thickness, superficial, and deep zones and from synovial cells, respectively. Thus, both chondrocytes and synovial cells bordering the joint cavity synthesize superficial zone protein and substantiate its usefulness as a phenotypic marker of particular cellular species lining the articular cavity.
We have performed cDNA sequencing and homology analyses to elucidate the complete amino acid composition for a superficial zone protein (SZP) from human and bovine cartilage which has previously been ...shown to be a proteoglycan specifically synthesized by chondrocytes located at the surface of bovine articular cartilage and also some synovial lining cells. The results of this study indicate that cartilage SZP is homologous with a glycoprotein first described as the precursor protein of a megakaryocyte stimulating factor (MSF). Sequence comparisons and analyses indicate that (i) the amino acid composition of SZP is highly conserved between bovine and human species, (ii) SZP contains structural motifs at the N- and C-termini which are similar to those found in vitronectin and which may impart cell-proliferative and matrix-binding properties to the molecule, and (iii) SZP contains large and small mucin-like repeat domains composed of the sequences KEPAPTTT/P (76–78 repeats) andXXTTTX(6–8 repeats), respectively, which occur within a large central region of ∼940 amino acids. The mucin-like domains are likely to be substituted with O-linked oligosaccharides which would impart lubricating properties to SZP which in part accumulates at the articular cartilage–synovial fluid interface. Additionally, we have shown that interleukin-1 inhibits the biosynthesis of chondrocyte SZP, while TGF-β and IGF-1 increase its biosynthesis, and that in pathological (osteoarthritic) human articular cartilage SZP mRNA can be expressed as an alternatively spliced variant lacking exons 4 and 5 which encode a potential heparin binding domain. The occurrence of different SZP alternative splice variants and the differential expression of SZP in the presence of cytokines and growth factors suggest that SZP may play an important cytoprotective role by preventing cellular adhesion to the articular cartilage surface in normal cartilage metabolism. Modifications to the structure of SZP, coupled with inhibition of SZP synthesis during inflammation, may account for the attachment and invasion of pannus observed in inflammatory joint diseases.
Osteoarthritis in ankle and knee joints Huch, Klaus; Kuettner, Klaus E.; Dieppe, Paul
Seminars in arthritis and rheumatism,
02/1997, Letnik:
26, Številka:
4
Journal Article
Recenzirano
Ankle and knee joints differ in their susceptibility to osteoarthritis (OA). This article reviews literature on differences between these joints. A Medline search and search of bibliographies of ...review articles was conducted. Knee cartilage degeneration leads to the development of OA with clinical symptoms, whereas the ankle cartilage develops fissures that do not appear to progress to later stages of OA. Epidemiological studies support these findings. Factors that might explain this phenomena include differences in joint motion, cartilage thickness, congruency, mechanical forces, and even evolutionary changes. Data suggest that chondrocytes from the two joints may respond differently to stimuli. Comparisons of cartilage from the knee and ankle joint of the same donor may provide a better understanding of the biochemical and molecular processes that induce the pathogenesis of OA and may provide new approaches to early detection and treatment.
Articular chondrocytes embedded in alginate gel produce de novo a matrix rich in collagens and proteoglycans. A major advantage of this culture system is that the cells can be recovered by chelating ...the calcium, which otherwise maintains the alginate in its gel state. Chondrocytes thus released are surrounded by tightly bound cell-associated matrix, which seems to correspond to the pericellular and territorial matrices identified in cartilage by electron microscopy. The cells and their associated matrix can be easily separated by mild centrifugation from more soluble matrix components derived principally from the 'interterritorial' matrix. This new cell culture system thus makes it possible to study the assembly and turnover of molecules present in two distinct matrix pools. Importantly, a significant proportion of the aggrecan molecules in each of these two pools can be extracted using a non-denaturing solvent, thereby making possible studies of the metabolism and turnover of native proteoglycan aggregates. We show in this report that chondrocytes isolated from the full depth of adult bovine articular cartilage and maintained for 8 months in alginate gel are still metabolically active and continue to synthesize cartilage-specific type II collagen and aggrecan. The cells did not synthesize large amounts of type I collagen or of the small nonaggregating proteoglycans as usually occurs when chondrocytes lose their phenotypic stability. After this extended period of time in culture, the cells were present as two populations exhibiting differences in size, shape and amount of extracellular matrix surrounding them. The first population was found only near the surface of the bead: these cells were flattened and surrounded by a matrix sparse in proteoglycans and collagen fibrils. The second population was found throughout the remaining depth of the bead: the cells were more round and almost always surrounded by a basket-like meshwork consisting of densely packed fibrils running tangential to the surface.
Regulation of osteogenic proteins by chondrocytes Chubinskaya, Susan; Kuettner, Klaus E
International Journal of Biochemistry and Cell Biology,
09/2003, Letnik:
35, Številka:
9
Book Review, Journal Article
Recenzirano
The purpose of this review is to summarize the current scientific knowledge of bone morphogenetic proteins (BMPs) in adult articular cartilage. We specifically focus on adult cartilage, since one of ...the major potential applications of the members of the BMP family may be a repair of adult tissue after trauma and/or disease. After reviewing cartilage physiology and BMPs, we analyze the data on the role of recombinant BMPs as anabolic agents in tissue formation and restoration in different in vitro and in vivo models following with the endogenous expression of BMPs and factors that regulate their expression. We also discuss recent transgenic modifications of BMP genes and subsequent effect on cartilage matrix synthesis. We found that the most studied BMPs in adult articular cartilage are BMP-7 and BMP-2 as well as transforming growth factor-β (TGF-β). There are a number of contradicting reports for some of these growth factors, since different models, animals, doses, time points, culture conditions and devices were used. However, regardless of the experimental conditions, only BMP-7 or osteogenic protein-1 (OP-1) exhibits the most convincing effects. It is the only BMP studied thus far in adult cartilage that demonstrates strong anabolic activity in vitro and in vivo with and without serum. OP-1 stimulates the synthesis of the majority of cartilage extracellular matrix proteins in adult articular chondrocytes derived from different species and of different age. OP-1 counteracts the degenerative effect of numerous catabolic mediators; it is also expressed in adult human, bovine, rabbit and goat articular cartilage. This review reveals the importance of the exploration of the BMPs in the cartilage field and highlights their significance for clinical applications in the treatment of cartilage-related diseases.
Objective The purpose of this work was to test the effect of inhibition of bone remodeling, through the use of the bisphosphonate, zoledronic acid, on cartilage matrix damage in an animal model of ...cartilage matrix damage.
Design New Zealand white rabbits were divided into four groups for treatment purposes: (1) untreated controls; (2) injected into one knee joint with the cartilage matrix degradation enzyme, chymopapain; (3) injected into one knee joint with chymopapain and also given subcutaneous injections of the bisphosphonate, zoledronic acid, three times per week until sacrifice at either day 28 or 56 post-chymopapain-injection; (4) received only the zoledronic acid injections. At sacrifice, the knee joints were examined grossly and histologically, and biochemically for proteoglycan content. Urine samples were analysed, at intervals, for levels of collagen cross-links which are biochemical markers of cartilage and bone.
Results Animals receiving both intraarticular chymopapain injections and subcutaneous zoledronic acid injections displayed a significantly lower degree of grossly and histologically detectable cartilage degeneration on the tibial articular surfaces (the articular surface displaying the greatest degree of degeneration) than did animals only receiving the chymopapain injections. In addition, urinary levels of collagen cross-links for bone and cartilage were significantly higher in those animals only receiving chymopapain injections.
Conclusion The bone resorption observed after chymopapain injection into the rabbit knee joint can be inhibited through the use of the bisphosphonate, zoledronic acid. Furthermore, zoledronic acid does not increase the level of cartilage degeneration and appears to provide some level of chondroprotection in this model.
Information on the prevalence and extent of degenerative morphological changes (DMC) in the joints of the lower extremity, including foot joints is sparse. In the present study, the first and fifth ...metatarsalphalangeal (MTP), transverse tarsal, subtalar, talocrural, knee and hip joints of 50 cadavers were examined grossly and graded on a five-point scale for signs of DMC. Selected samples were examined histologically. Our results confirm clinical findings that severe DMC in foot joints are uncommon except in the first MTP joint where the plantar aspect is most affected. The knee joint displayed the most numerous and severe signs of DMC followed by the first MTP joint. The hip, talocrural, subtalar and transverse tarsal joints displayed comparatively moderate levels of DMC while the fifth MTP was rarely affected. The only joint to display significantly greater levels of DMC on the distal side of the joint as compared with the proximal side, when a difference was present, was the hip. There were significantly greater levels of DMC on the medial aspect of two or more joints within an extremity than on the lateral aspect. Radiographs often showed few or no signs of DMC even when erosion down to subchondral bone was observed upon gross examination.
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