Showing papers on "Cartilage published in 1987"

Role of transforming growth factor-beta in the development of the mouse embryo.

Abstract: Using immunohistochemical methods, we have investigated the role of transforming growth factor-beta (TGF-beta) in the development of the mouse embryo. For detection of TGF-beta in 11-18-d-old embryos, we have used a polyclonal antibody specific for TGF-beta type 1 and the peroxidase-antiperoxidase technique. Staining of TGF-beta is closely associated with mesenchyme per se or with tissues derived from mesenchyme, such as connective tissue, cartilage, and bone. TGF-beta is conspicuous in tissues derived from neural crest mesenchyme, such as the palate, larynx, facial mesenchyme, nasal sinuses, meninges, and teeth. Staining of all of these tissues is greatest during periods of morphogenesis. In many instances, intense staining is seen in mesenchyme when critical interactions with adjacent epithelium occur, as in the development of hair follicles, teeth, and the submandibular gland. Marked staining is also seen when remodeling of mesenchyme or mesoderm occurs, as during formation of digits from limb buds, formation of the palate, and formation of the heart valves. The presence of TGF-beta is often coupled with pronounced angiogenic activity. The histochemical results are discussed in terms of the known biochemical actions of TGF-beta, especially its ability to control both synthesis and degradation of both structural and adhesion molecules of the extracellular matrix.

Effects of Immobilization on Joints

Abstract: Stress deprivation alters the morphologic, biochemical, and biomechanical characteristics of various components of synovial joints. Prominent among the protean changes that result are proliferation of fibrofatty connective tissue within the joint space, adhesions between synovial folds, adherence of fibrofatty connective tissue to cartilage surfaces, atrophy of cartilage, "ulceration" at points of cartilage-cartilage contact, disorganization of cellular and fibrillar ligament alignment, weakening of ligament insertion sites owing to osteoclastic resorption of bone and Sharpey's fibers, regional osteoporosis of the involved extremity, increased force requirement for joint cycling, and increased ligament compliance. Reduced load-to-failure and reduced energy-absorbing capacity of the bone-ligament-bone complex progresses to about one-third that of controls. Collagen mass declines by about 10%. Collagen turnover increases with accelerated degradation and synthesis. Formation of reducible collagen crosslinks increases. Content of proteoglycan, notably hyaluronic acid, falls and water content is correspondingly reduced. An understanding of the functional implications of these extensive perturbations in the phenomenon of joint immobilization is essential for progress in orthopedics.

Tenascin is associated with chondrogenic and osteogenic differentiation in vivo and promotes chondrogenesis in vitro.

Abstract: The tissue distribution of the extracellular matrix glycoprotein, tenascin, during cartilage and bone development in rodents has been investigated by immunohistochemistry. Tenascin was present in condensing mesenchyme of cartilage anlagen, but not in the surrounding mesenchyme. In fully differentiated cartilages, tenascin was only present in the perichondrium. In bones that form by endochondral ossification, tenascin reappeared around the osteogenic cells invading the cartilage model. Tenascin was also present in the condensing mesenchyme of developing bones that form by intramembranous ossification and later was present around the spicules of forming bone. Tenascin was absent from mature bone matrix but persisted on periosteal and endosteal surfaces. Immunofluorescent staining of wing bud cultures from chick embryos showed large amounts of tenascin in the forming cartilage nodules. Cultures grown on a substrate of tenascin produced more cartilage nodules than cultures grown on tissue culture plastic. Tenascin in the culture medium inhibited the attachment of wing bud cells to fibronectin-coated substrates. We propose that tenascin plays an important role in chondrogenesis by modulating fibronectin-cell interactions and causing cell rounding and condensation.

Quantitation of Chondrocyte Performance in Growth-Plate Cartilage during Longitudinal Bone Growth*

Abstract: The longitudinal growth of bone depends on the activities of individual chondrocytes of the growth plate. Each chondrocyte remains in a fixed location throughout its life, and there accomplishes all of its functions. Although a cell may perform several or all of its activities simultaneously, one of these will usually predominate during a particular phase of its life. The two most prominent stages are those of cellular proliferation and hypertrophy (including the mineralization of matrix) before the resorption of tissue during vascular invasion. By applying recently developed stereological procedures and improved methods for the fixation of cartilage, we compared cellular shape modulation, various ultrastructural parameters (surface areas or volumes of endoplasmic reticulum, Golgi membranes, and mitochondria), the production of matrix, and cellular turnover for proliferating and hypertrophic chondrocytes within the proximal tibial growth plate of the rat. By the late hypertrophic stage, fourfold and tenfold increases in the mean cellular height and volume, respectively, and a threefold increase in the mean volume of the matrix per cell were achieved. The high metabolic activity of hypertrophic cells was reflected by a twofold to fivefold increase in the mean cellular surface area of rough endoplasmic reticulum, the Golgi membranes, and the mean cellular mitochondrial volume. Rates of longitudinal growth were determined by fluorochrome labeling and incident-light fluorescence microscopy. Using these values and the stereological estimators describing cellular height, the rates of cellular turnover were calculated. The rapid progression of the vascular invasion front was found to eliminate, for each column of cells, one chondrocyte every three hours; that is, eight cells a day. The maintenance of a steady-state structure for growth-plate cartilage in rats in a steady state of growth thus necessitates efficient compensation for these losses, which is achieved by a high rate of cellular proliferation and rapid hypertrophy.

The Effect of Proteoglycans on the Morphology of Collagen Fibrils Formed In Vitro

Abstract: The morphology of collagen fibrils at various times during formation in vitro was quantitatively examined by negative staining and by scanning electron microscopy. The presence of a small dermatan sulfate proteoglycan from bovine tendon (5 micrograms proteoglycan/100 micrograms collagen) resulted in collagen fibrils that were significantly thinner in width at all times by both methodologies. The rate of fibril diameter increase was also retarded by the small proteoglycans, suggesting that they inhibited the lateral aggregation of forming collagen fibrils. Large proteoglycans from cartilage did not produce this effect.

Localization of types I, II, and III collagen mRNAs in developing human skeletal tissues by in situ hybridization.

Abstract: Paraffin sections of human skeletal tissues were studied in order to identify cells responsible for production of types I, II, and III collagens by in situ hybridization. Northern hybridization and sequence information were used to select restriction fragments of cDNA clones for the corresponding mRNAs to obtain probes with a minimum of cross-hybridization. The specificity of the probes was proven in hybridizations to sections of developing fingers: osteoblasts and chondrocytes, known to produce only one type of fibrillar collagen each (I and II, respectively) were only recognized by the corresponding cDNA probes. Smooth connective tissues exhibited variable hybridization intensities with types I and III collagen cDNA probes. The technique was used to localize the activity of type II collagen production in the different zones of cartilage during the growth of long bones. Visual inspection and grain counting revealed the highest levels of pro alpha 1(II) collagen mRNAs in chondrocytes of the lower proliferative and upper hypertrophic zones of the growth plate cartilage. This finding was confirmed by Northern blotting of RNAs isolated from epiphyseal (resting) cartilage and from growth zone cartilage. Analysis of the osseochondral junction revealed virtually no overlap between hybridization patterns obtained with probes specific for type I and type II collagen mRNAs. Only a fraction of the chondrocytes in the degenerative zone were recognized by the pro alpha 1(II) collagen cDNA probe, and none by the type I collagen cDNA probe. In the mineralizing zone virtually all cells were recognized by the type I collagen cDNA probe, but only very few scattered cells appeared to contain type II collagen mRNA. These data indicate that in situ hybridization is a valuable tool for identification of connective tissue cells which are actively producing different types of collagens at the various stages of development, differentiation, and growth.

Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology.

Abstract: Immunization with chondroitinase ABC-digested fetal human cartilage proteoglycan and Freund's complete adjuvant induced polyarthritis and ankylosing spondylitis in female BALB/c mice. The initial external symptoms of the joint inflammation were swelling and redness. This was associated with edema of the synovium and periarticular tissues and gross proliferation of cells, which reached a peak during weeks 7-9 of the experiment. Mononuclear cell infiltration, with perivascular concentration and occlusion of small vessels, was common. Synovitis increased in severity, villous pannus developed, and erosions of bone, articular cartilage, and occasionally, growth plate were observed. The lumbar spine and the proximal intervertebral discs of the tail also exhibited inflammatory and degenerative changes. As the arthritis progressed, sometimes with acute inflammatory exacerbations, more joints became involved and, by the sixteenth to the twentieth weeks of the experiment, a progressive polyarthritis, with gross joint deformities and restricted function, developed in the majority of the limb joints. Clinical and morphologic features of the disease correlated well with radiologic analysis and with an increased deposition of 99mTc-methylene diphosphonate (determined by radionuclide imaging). The development of this arthritis was accompanied by the expression of cell-mediated and humoral immunity to the immunizing antigen. However, this immunity was also observed, although it was generally less well developed, in mice that received the intact or digested proteoglycan without adjuvant. These mice did not usually develop arthritis. Control mice that received only adjuvant did not develop arthritis.

Technique for healing lesions in cartilage

Abstract: A grafting technique entailing the transplantation of chondrocytes for promoting the healing of lesions in articular cartilage, use being made for this purpose of in vitro autologous cultured chondrocytes prior to transplantation. The chondrocytes are preferably seeded in a three-dimensional collagen matrix which serves as the graft material. In order to internally fix the graft during the healing process, use is made of a periosteal flap which is sutured to the cartilage after the graft material is implanted therein.

Influences of mechanical stress on prenatal and postnatal skeletal development.

Abstract: A new theory is introduced to describe some of the influences of mechanical stresses on chondroosseous biology. It is proposed that degeneration and ossification is a normal process for all cartilage in the appendicular skeleton, which is accelerated by intermittently applied shear stresses (or strain energy), and inhibited or prevented by intermittently applied hydrostatic pressure. These concepts were applied using finite element computer models in an effort to predict the ossification pattern of the prenatal and postnatal femoral anlage. The theoretical calculations successfully predicted the key features of skeletal morphogenesis including the development of the primary ossification site, a tubular diaphysis and marrow cavity, metaphyseal and epiphyseal trabecular bone, the location and geometry of the growth plate, the appearance and location of the secondary ossific nucleus, and the existence and thickness distribution of articular cartilage. The results suggest that degenerative joint disease in immobilized or nonload-bearing mature joints may be a manifestation of the final stage in the ossification of the anlage. In nonfunctional joints, the absence or reduction of intermittent hydrostatic pressure in the articular cartilage permits cartilage degeneration and the progressive advance of the ossification front toward the joint surface until the articular cartilage has been ossified.

Weight bearing controls glycosaminoglycan concentration and articular cartilage thickness in the knee joints of young beagle dogs

Abstract: Casting of the right knee (stifle) joints of young beagle dogs for 11 weeks caused up to 48% reduction in the glycosaminoglycan (GAG) concentration of the uncalcified articular cartilage, as assessed by a new microspectrophotometric method. The GAGs were depleted mainly in the superficial zone of the cartilage. Although the thickness of the uncalcified cartilage was not decreased, the calcified cartilage under the tidemark was thinned by 6-25% at the femoral condyles. The increased weight-bearing in the limb opposite the one in the splint caused uncalcified cartilage thickness to be augmented by 19% and GAG concentration by 25-35% in the intermediate, deep, and calcified zones of the summits of the femoral condyles; the changes were smaller in other, less loaded parts of the joint. It is concluded that in young dogs, increased weight-bearing augments local proteoglycan content of the articular cartilage matrix, while unloading reduces it.

Use of cultured embryonal chick epiphyseal chondrocytes as grafts for defects in chick articular cartilage.

Abstract: Full-thickness defects in articular cartilage were repaired with cultured homologous embryonic chick epiphyseal chondrocytes embedded in a biological resorbable immobilization vehicle (BRIV). This graft was successfully transplanted in mechanically induced defects in the surface of condylar articular cartilage of the tibiotarsal joint of four-month-old roosters. Healing of the defects was observed macroscopically, histologically, and histochemically and with the use of biochemical analyses for six months. Chondrocyte proliferation was seen 48 hours after implantation, and a hyaline cartilage matrix surrounding the cells was present two weeks later. Within eight weeks, the defects were completely filled with hyaline cartilage, which integrated smoothly with the neighboring cartilage without the formation of fibrous tissue at the interface. The cell content and rate of proteoglycan synthesis remained high for four months, then declined slowly to the level of the surrounding cartilage. Six months after transplantation, the cartilaginous tissue in the wound at levels below the ossification front showed penetration by vascular elements and young bone trabeculae at the margins of the reparative tissue. No signs of immunogenic rejection of the implants were observed. These results may be related to the employment of a capable source of cells, i.e., cultured chondrocytes characterized by a high mitotic rate and an early stage of development. The transplanted cells grew well and maintained their initial rate of proliferation, with definite maturation and transformation. The resulting cartilage was structurally reorganized according to the host pattern and under the influence of multitudinous environmental conditions. The articular zone preserved its cartilaginous phenotype, whereas the subchondral regions were transformed into bone.

Arthroscopic and immunohistologic characterization of knee joint synovitis in osteoarthritis.

Abstract: We studied 10 patients who had arthritis of the knee joint, but no other signs of rheumatic disease. The clinical diagnosis of osteoarthritis was corroborated by arthroscopic evidence of characteristic cartilage degeneration. Signs of inflammation were confined to areas of the synovial membrane that lay near the cartilage; thus, the major part of the joint cavity was not affected. The intensity of the synovial inflammation varied within the areas involved, but was always most pronounced in regions rimming the cartilage. Biopsy samples selected from regions of intensely inflamed synovium contained foci of T lymphocytes, which were bordered by immunoglobulin-carrying B lymphocytes and plasma cells, as well as strongly HLA-DR positive dendritic-like cells adjoined to alpha Leu-3a+ T helper lymphocytes. In tissue samples taken from macroscopically noninflamed areas, only a few infiltrating lymphocytes were seen. Thus, the inflammatory synovial changes found in osteoarthritis appear to be anatomically restricted and of varied intensity but, when present, are microscopically indistinguishable from the changes that have been previously described as indicative of rheumatoid arthritis.

Immunity to cartilage proteoglycans in balb/c mice with progressive polyarthritis and ankylosing spondylitis induced by injection of human cartilage proteoglycan

Abstract: Intraperitoneal injection of human fetal cartilage proteoglycan (depleted of chondroitin sulfate) in Freund's complete or incomplete adjuvant induces a chronic erosive polyarthritis and spondylitis in all female BALB/c mice. This occurrence is strain-specific but not haplotype-specific, and it is sex-related. The development of the arthritis is associated with the natural presence of cellular immunity to the immunizing antigen and to chondroitinase ABC-treated mouse cartilage proteoglycan. In addition, relatively more antibody to the immunizing proteoglycan is elicited in arthritic mice, and antibodies are produced that cross-react with native mouse proteoglycan. This combination of immune responses is not observed in mice that do not develop arthritis. Associated with the arthritis is the development of cytotoxicity to mouse chondrocytes and, in some animals, of rheumatoid factor, immune deposits in joint tissues and kidneys, and the production of autoantibodies to mouse type II collagen. These observations might be related to our earlier demonstration that immunity to human cartilage proteoglycan is observed in some patients with ankylosing spondylitis.

Extended and globular protein domains in cartilage proteoglycans.

Abstract: Electron microscopy after rotary shadowing and negative staining of the large chondroitin sulphate proteoglycan from rat chondrosarcoma, bovine nasal cartilage and pig laryngeal cartilage demonstrated a unique multidomain structure for the protein core. A main characteristic is a pair of globular domains (diameter 6-8 nm), one of which forms the N-terminal hyaluronate-binding region. They are connected by a 25 nm-long rod-like domain of limited flexibility. This segment is continued by a 280 nm-long polypeptide strand containing most chondroitin sulphate chains (average length 40 nm) in a brush-like array and is terminated by a small C-terminal globular domain. The core protein showed a variable extent of degradation, including the loss of the C-terminal globular domain and sections of variable length of the chondroitin sulphate-bearing strand. The high abundance (30-50%) of the C-terminal domain in some extracted proteoglycan preparations indicated that this structure is present in the cartilage matrix rather than being a precursor-specific segment. It may contain the hepatolectin-like segment deduced from cDNA sequences corresponding to the 3′-end of protein core mRNA [Doege, Fernandez, Hassell, Sasaki & Yamada (1986) J. Biol. Chem. 261, 8108-8111; Sai, Tanaka, Kosher & Tanzer (1986) Proc. Natl. Acad. Sci. 83, 5081-5085; Oldberg, Antonsson & Heinegard (1987) Biochem. J. 243, 255-259].

The effect of antibiotics on the destruction of cartilage in experimental infectious arthritis.

Abstract: In joints with bacterial arthritis, continuing prolonged destruction of cartilage may occur in spite of prompt, effective antibiotic therapy. We measured the extent to which early antibiotic therapy with ceforanide altered the degradation of the cartilage after arthritis due to Staphylococcus aureus had been produced in the knee joint in rabbits. Degradation of the cartilage was quantified by analyses for glycosaminoglycan and collagen. Three weeks after the infection was produced, the cartilage had lost more than half of its glycosaminoglycan whether the antibiotic therapy had been started at one, two, or seven days after infection. Beginning the antibiotic treatment one day after infection reduced over-all loss of collagen by 37 per cent and decreased the area of erosion of the infected articular surfaces. When antibiotic treatment was begun at four, eight, or twelve hours after infection, the loss of glycosaminoglycan averaged 18 per cent. Prophylaxis with antibiotics completely prevented any degradation of the cartilage. Clinical relevance: The findings reported here show how rapidly cartilage loses glycosaminoglycan when it is involved by arthritis caused by staphylococci and how early treatment of the infection reduces the loss of collagen. There is less protection against loss of glycosaminoglycan. The results emphasize the need for early diagnosis and treatment of infectious synovitis and support the rationale for early administration of antibiotics without waiting for identification of the responsible bacteria.

The spatial and temporal pattern of collagens I and II and keratan sulphate in the developing chick metatarsophalangeal joint.

Abstract: Both intrinsic and extrinsic factors are known to be involved in the morphogenesis of diarthrodial joints. The use of specific antibodies to collagens I and II and keratan-sulphate-containing proteoglycans (KSPG) has enabled the distributions of these macromolecules to be followed during the development of the third metatarsophalangeal joint in the chicken embryo. Our study shows that cartilage differentiation occurs as a continuous rod, which is then subsequently divided into separate elements. Further development also reveals that, unlike the matrix of the cartilaginous elements, there is a differential distribution of collagen (type II) and KSPG in the presumptive joint region. It is proposed that a decrease in KSPG in the presumptive joint region at stages 28/30 may be involved in the mechanism for the flattening of cells in formation of the interzone. Whereas, a decrease in collagen across the joint interzone region may provide an area of weakness, which might allow forces produced by the developing musculature to cause cavitation.

Further characterisation of the extracellular matrix in the mandibular condyle in neonatal mice.

Abstract: This study provides newer information concerning the extracellular matrix of neonatal condylar cartilage--a genuine representative of a secondary type of cartilage. In addition, the data presented hereby indicate that the condylar cartilage contains a population of progenitor cells that synthesise Type I collagen rather than Type II. Under normal conditions in vivo local biomechanical factors influence the progenitor cells to differentiate into cartilage cells and thereby to shift their synthetic pathway from Type I collagen to Type II collagen--the typical collagen of cartilage extracellular matrix. In the absence of such biomechanical effects the condylar progenitor cells seem to proceed with their inherent differentiation pathway and express an osteogenic phenotype (Fig. 21).

The proteoglycanase from human cartilage and cultured rabbit chondrocytes and its relation to osteoarthritis.

Abstract: The neutral metal dependent proteoglycanase predominates as the chief neutral protease present in human patellar cartilage or released by cultured rabbit chondrocytes into the culture medium. The cultured chondrocytes released the proteoglycanase mostly in latent form. Its activation resulted in splitting off a 10,000 dalton fragment. The chondrocytes also released inhibitory activity against the proteoglycanase. Most of it was released in the first 24 hours of culture, while most of the enzyme was released in the following 48 hours. Both the human cartilage and the rabbit chondrocyte enzyme occur in two molecular weight sizes, in equilibrium with each other.

A major, six-armed glycoprotein from embryonic cartilage.

Abstract: Here we describe the isolation and identification of a major cartilage glycoprotein which is co-extracted along with typical hyaline cartilage components such as collagen types II and IX from chicken embryo sternum In polyacrylamide gel electrophoresis it migrates as a high molecular mass protein (greater than 10(6) daltons) which on reduction gives rise to a prominent doublet at 205/195 kd and minor bands at 220 and 170 kd The intact molecule sediments as a 13S component in rate zonal centrifugation, indicative of a highly extended conformation in solution In these properties it closely resembles myotendinous antigen, a glycoprotein recently detected in a number of embryonic tissues, including cartilage This identity was confirmed by immunoblotting using a monoclonal antibody (M1) specific for myotendinous antigen Electron micrographs of the rotary shadowed molecule revealed an unusual six-armed structure, indistinguishable in form and dimensions from hexabrachion, a recently discovered contaminant of cellular fibronectin preparations These structures could be decorated with the M1-antibody, demonstrating that hexabrachion is myotendinous antigen This extended, potentially multivalent molecule could provide an ideal substrate to connect widely spaced components in a highly hydrated tissue such as cartilage

Epithelial-mesenchymal interactions in the development of chick facial primordia and the target of retinoid action.

Abstract: The development of the chick face involves outgrowth of buds of tissue, accompanied by the differentiation of cartilage and bone in spatially defined patterns. To investigate the role of epithelial-mesenchymal interactions in facial morphogenesis, small fragments of facial tissue have been grafted to host chick wing buds to continue their development in isolation. Fragments of the frontonasal mass give rise to typical upper-beak-like structures: a long central rod of cartilage, the prenasal cartilage and an egg tooth. Meckel's cartilage, characteristic of the lower beak, develops from fragments of the mandible. Removal of the ectoderm prior to grafting leads to truncated development. In fragments of frontonasal mass mesenchyme only a small spur of cartilage differentiates and there is no outgrowth. The mandible is less affected; a rod of cartilage still forms but the amount of outgrowth is reduced. Retinoid treatment of chick embryos specifically affects the development of the upper beak and outgrowth and cartilage differentiation in the frontonasal mass are inhibited. The mandibles, however, are unaffected and develop normally. In order to investigate whether the epithelium or the mesenchyme of the frontonasal mass is the target of retinoid action, recombinations of retinoid-treated and untreated facial tissue have been grafted to host wing buds. Recombinations of retinoid-treated frontonasal mass ectoderm with untreated mesenchyme develop normally whereas recombinations of untreated ectoderm with retinoid-treated mesenchyme lead to truncations. The amount of outgrowth in fragments of mandibular tissue is slightly reduced when either the ectoderm or the mesenchyme has been treated with retinoids. These recombination experiments demonstrate that the mesenchyme of the frontonasal mass is the target of retinoid action. This suggests that retinoids interfere with the reciprocal epithelial-mesenchymal interactions necessary for outgrowth and normal upper beak development.

Articular cartilage defects: detectability in cadaver knees with MR

Abstract: The capability of 1.5-T MR imaging to detect focal defects in articular cartilage was investigated with cadaveric knees with and without intraarticular injection of saline and gadolinium-DTPA (Gd-DTPA). Full-thickness cartilage lesions ranging in diameter from 1 to 5 mm were surgically created in the femoral articular surfaces. Images were acquired with a variety of pulse techniques, slice thicknesses, and interslice gaps as well as one or two signal excitations. Potential intraarticular contrast agents (saline and Gd-DTPA) were tested, and their signal behaviors compared with that of hyaline cartilage. All cartilage defects were occult on T1-weighted and balanced images without Gd-DTPA. The smallest defect identified by using intraarticular saline was 3 mm in diameter and was apparent only on T2-weighted images. Intraarticular Gd-DTPA afforded detection of defects as small as 2 mm, even with short imaging times. Signal-intensity differences between saline and articular cartilage were minimal on T1-weight...

Healing of experimentally produced lesions in articular cartilage following chondrocyte transplantation.

Abstract: Articular cartilage is known to have limited ability to heal once injured, and attempts to heal lesions in cartilage have yielded equivocal results. The following experiments were performed to investigate healing in cartilage following transplantation of chondrocytes grown in vitro. The knee joint of the New Zealand White rabbit was used as the experimental model. An initial baseline study was made to determine the intrinsic capability of cartilage for healing defects that do not fracture the subchondral plate. A second experiment examined the effects of autologous in vitro grown chondrocytes on the healing rates of these defects. The results were evaluated by qualitative and quantitative light microscopy. In control defects not grafted with chondrocytes, 6 weeks after the initial defect was created, there was little repair. Macroscopic and histological findings were consistent with an osteoarthritic pathology such as synovitis and “cell nests.” Macroscopic results from grafted specimens displayed a marked decrease in synovitis and other degenerative changes. Defects which had received transplants had a significant amount of cartilage reconstituted (82%) compared to ungrafted controls (18%). Controls showed a healing rate comparable to that obtained in the initial baseline study.

The immunologic detection and characterization of cartilage proteoglycan degradation products in synovial fluids of patients with arthritis.

Abstract: Antibodies were used in radioimmunoassays with gel chromatography to detect the hyaluronic acid-binding region, core protein, and keratan sulfate of human cartilage proteoglycan in the synovial fluids of patients with rheumatoid arthritis, juvenile rheumatoid arthritis, and osteoarthritis. All fluids contained proteoglycan that was mainly included on Sepharose CL-4B; this result indicates cleavage of proteoglycan (which is normally excluded). The hyaluronic acid-binding region was the smallest and most commonly detected fragment. It was relatively free of keratan sulfate and core protein, and it could sometimes bind to hyaluronic acid. Other larger fragments containing core protein and/or keratan sulfate were detected in every fluid.