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Neoplastic invasion of laryngeal cartilage: the significance of cartilage sclerosis on computed tomography images.

Cartilage sclerosis has been cited as a sensitive and a specific sign of neoplastic cartilage invasion, on cross-sectional computed tomography (CT) images of the larynx. We retrospectively reviewed 36 consecutive patients, who underwent a total laryngectomy for squamous cell carcinoma of the larynx. Preoperative CT images were compared with formal histological sections of the larynx in order to assess cartilage invasion by tumour. Isolated asymmetrical cartilage sclerosis was found to have a sensitivity of 62% and a specificity of 42% for predicting neoplastic cartilage invasion when compared with histopathological sections of the tumour. In this study we found that cartilage sclerosis was not a useful early radiological sign of neoplastic cartilage invasion when taken in isolation.

Arytenoid Cartilage↗

Lateral division of the rabbit cricoid cartilage: its effect on cartilage growth.

Laryngotracheoplasty often includes bilateral lateral division of the cricoid cartilage, despite the theoretical risk that cartilage growth centers might be located in the lateral cricoid. To investigate the effect of lateral cricoid cartilage division on subsequent cartilage growth, 60 five-week-old New Zealand white rabbits were divided into four groups of 15 animals each. Group I was comprised of unoperated controls. The remaining animals underwent anterior (group II), anterior and posterior (group III), and anterior, posterior, and bilateral lateral (group IV) division of the cricoid cartilage. Animals were killed 20 weeks after surgery, and the cross-sectional area of each animal's cricoid cartilage and of each animal's airway was determined. There was no statistically significant difference in mean cartilage cross-sectional area between any of the four groups; the group IV mean was larger than that of any other group, though the difference was not significant. There was no significant difference in airway cross-sectional area between any of the groups operated on. From these results, lateral cricoid division in the growing animal does not appear to interfere with subsequent normal growth of the larynx.

Animals↗

Improved cartilage integration and interfacial strength after enzymatic treatment in a cartilage transplantation model.

The objective of the present study was to investigate whether treatment of articular cartilage with hyaluronidase and collagenase enhances histological and mechanical integration of a cartilage graft into a defect. Discs of 3 mm diameter were taken from 8-mm diameter bovine cartilage explants. Both discs and annulus were either treated for 24 hours with 0.1% hyaluronidase followed by 24 hours with 10 U/ml collagenase or left untreated (controls). Discs and annulus were reassembled and implanted subcutaneously in nude mice for 5 weeks. Integration of disc with surrounding cartilage was assessed histologically and tested biomechanically by performing a push-out test. After 5 weeks a significant increase in viable cell counts was seen in wound edges of the enzyme-treated group as compared with controls. Furthermore, matrix integration (expressed as a percentage of the total interface length that was connected; mean +/- standard error) was 83 +/- 15% in the treated samples versus 44 +/- 40% in the untreated controls. In the enzyme-treated group only, picro-Sirius Red staining revealed collagen crossing the interface perpendicular to the wound surface. Immunohistochemical analyses demonstrated that the interface tissue contained cartilage-specific collagen type II. Collagen type I was found only in a small region of fibrous tissue at the level of the superficial layer, and collagen type III was completely absent in both groups. A significant difference in interfacial strength was found using the push-out test: 1.32 +/- 0.15 MPa in the enzyme-treated group versus 0.84 +/- 0.14 MPa in the untreated controls. The study shows that enzyme treatment of cartilage wounds increases histological integration and improves biomechanical bonding strength. Enzymatic treatment may represent a promising addition to current techniques for articular cartilage repair.

Animals↗

Auricular cartilage versus costal cartilage as a grafting material in experimental laryngotracheal reconstruction.

Auricular cartilage has been used clinically as an alternative material to costal cartilage for implantation during laryngotracheal reconstructive surgery. Little information is available concerning the healing characteristics or the durability of these two types of graft. The authors of this study examined the rate of epithelialization and the survival of cartilage in a rabbit model of anterior tracheal wall reconstruction and directly compared auricular and costal cartilage grafts. Auricular cartilage was found to epithelialize faster than costal cartilage. Both types of graft survived well after implantation. The superior healing characteristics of auricular cartilage make it a desirable material for laryngotracheal reconstruction.

Animals↗

Surgical removal of articular cartilage leads to loss of chondrocytes from cartilage bordering the wound edge.

BACKGROUND: A number of arthroscopic procedures that are used in the treatment of focal cartilage lesions or osteoarthritic joints, such as shaving, débridement, and laser abrasion, involve the removal of both diseased and healthy articular cartilage. The excision of such tissue has the effect of generating lesions within the articular cartilage. The fate of the chondrocytes that border such lesions has not been evaluated. The purpose of this investigation was to ascertain whether the surgical creation of lesions in articular cartilage induces irreversible loss of chondrocytes over time from tissue bordering the wound edge and to determine whether the synthetic activity of cells in this region is compromised. METHODS: Partial-thickness defects of defined dimensions were created in the femoral condyle and/or trochlear groove of rabbits and miniature pigs. Cell volumes, cell volume densities, and numerical cell densities within tissue close to (within 100 micro m) and remote from (control site) the wound edge were determined by quantitative histomorphometry at various time intervals up to six months after surgery. Rates of proteoglycan synthesis by cells in both regions were determined by quantitative autoradiography following (35) S-sulphate labeling in vivo. RESULTS: The surgical creation of partial-thickness lesions in articular cartilage induced a significant and long-term loss of cells from tissue near the wound edge. However, the surviving cell population maintained a normal rate of matrix proteoglycan deposition. CONCLUSIONS: This study illustrates that maintenance and remodeling of cartilage matrix close to wound edges in articular cartilage lesions is compromised, since fewer cells, with an unchanged metabolic activity rate, are left to sustain matrix domains.

Animals↗

Articular cartilage explant culture; an appropriate in vitro system to compare osteoarthritic and normal human cartilage.

Proteoglycan metabolism of normal and histologically mild to moderate osteoarthritic cartilage explants were studied. Explants were obtained from the human knee of donors aged over 40 years. Proteoglycan content, synthesis and release were very similar in normal cartilage obtained from donors with focal osteoarthritis and cartilage obtained from donors without any sign of osteoarthritis. This suggests that cartilage obtained from donors with focal osteoarthritis indeed can be considered as "normal". The relatively large surface area-compared to their natural setting in the joint- of cartilage explants in culture did not affect the parameters measured, as there was a strong linear correlation between these parameters and the weight of the explants. From our results, we conclude that the use of full depth cartilage tissue explants is a reliable way to assess and compare proteoglycan content, synthesis and release in normal and osteoarthritic cartilage from the same donor.

Adult↗

Lubricin reduces cartilage--cartilage integration.

Cartilage integration in vivo does not occur, such that even cartilage fissures do not heal. This could be due not only to the limited access of chondrocytes to the wound, but also to exogenous factors. In this paper, we tested the hypothesis that lubricin, a lubricating protein physiologically present in the synovial fluid, reduces the integrative cartilage repair capacity. Disk/ring composites of bovine articular cartilage were prepared using concentric circular blades and cultured for 6 weeks with or without treatment with 250 microg/ml lubricin applied three times per week. Following culture, the percentage of contact area between the disks and the rings, as assessed by light microscopy, were equal in both groups. The adhesive strength of the integration interface, as assessed by push-out mechanical tests, was markedly and significantly lower in lubricin-treated specimens (2.5 kPa) than in the controls (28.7 kPa). Histological observation of Safranin-O stained cross-sections confirmed the reduced integration in the lubricin treated composites. Our findings suggest that the synovial milieu, by providing lubrication of cartilage surfaces, impairs cartilage--cartilage integration.

Animals↗

Human facet cartilage: swelling and some physico-chemical characteristics as a function of age. Part 1: Swelling of human facet joint cartilage.

The hydration of cartilage from human facet joints was measured after the joints had been subjected to different treatments. One group of facets was opened and directly exposed to physiologic saline solution before extraction of cartilage plugs. The plugs were weighed, re-equilibrated in fluid, and weighed again. The swelling results obtained under these conditions were compared with those when similar plugs of cartilage were excised from joints that had not been exposed to solution or had been exposed to solution while still closed. It was found that swelling was least (and similar in value to hip cartilage) for joints that had been exposed open to saline solution, highest for joints that had not been exposed to solution, and intermediate for joints that had been exposed to solution while still closed. The same trends were observed whether the cartilage on the joint was intact or fibrillated, although in each group the swelling and the final hydration were higher for fibrillated than for intact tissue. It was concluded that facet cartilage, unlike human hip or knee cartilage, is underhydrated when excised from the joint. This underhydration is thought to reflect the permanent presence of stresses in vivo on some part of the facet joints, the position of the loaded site changing with time. The authors attempted to distinguish between the swelling caused by this underhydration and that from disruption of the collagen network in the case of fibrillated specimens.

Aging↗

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

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

Alprostadil↗

Biochemical changes in articular cartilage opposing full- and partial-thickness cartilage lesions in horses.

Using arthroscopic technique, identical diameter defects were created in the proximal articular surface of both intermediate carpal bones of 6 horses. One of each pair of defects was deepened to penetrate the subchondral plate. Removed cartilage was assayed for [35S] sulfate incorporation, total hexosamine content, and DNA content. Six weeks later, cartilage was harvested and similarly analyzed from the distolateral portion of the radius directly opposite the created lesions and the distomedial portion of the radius distant from the lesion. The repair tissue filling the full-thickness defect and the cartilage at the periphery of the partial-thickness lesion also were analyzed. There was a marked increase in synthetic activity (35S sulfate incorporation) opposite the full-thickness defect, compared with the cartilage opposite the partial-thickness defect. A marked decrease in glycosaminoglycan content in the cartilage opposite the full-thickness defect was found as compared with that opposite the partial-thickness defect. The repair tissue filling the full-thickness defect was highly cellular, high in synthetic activity, but low in glycosaminoglycan content. Insignificant changes occurred in the cartilage adjacent to the partial-thickness defect. On the basis of these results, we suggest that full-thickness defects at 6 weeks result in more detrimental change to the cartilage opposite it than do partial-thickness lesions of the same diameter.

Animals↗

[Glucosamine: its importance for the metabolism of articular cartilage. 2. Studies on articular cartilage].

In healthy individuals there exists a balance between cartilage proteoglycan synthesis and degradation. In arthrotic cartilage this metabolic balance is deteriorated in spite of a sometimes enhanced proteoglycan synthesis, since the catabolic rate exceeds the anabolic rate corresponding to the severity of the disease. The extracellular organic matrix of the cartilage is destroyed. With different experimental models it could be demonstrated, that the non steroidal anti-inflammatory drugs commonly used in the treatment of arthrosis inhibit the synthesis of mucopolysaccharides, intensify the already existing metabolic disorder, prevent a normalization of cartilage composition and thus impair the function of the cartilage. Glucosamine on the other hand increases in a dose-dependent way the ability of cartilage to synthesize both sulfated mucopolysaccharides and protein, thus restoring the catabolic-anabolic balance of the cartilage.

Animals↗

Absence of proteoglycan core protein in cartilage from the cmd/cmd (cartilage matrix deficiency) mouse.

Mice homozygous for the autosomal recessive gene, cartilage matrix deficiency (cmd/cmd), are characterized by disproportionate dwarfism and cleft palate. The collagen and proteoglycan of fetal limb cartilage was examined by biochemical and immunofluorescent techniques. While a normal amount of type II collagen was found, the amount of proteoglycan was reduced as determined by chemical analysis and incorporation of labeled precursors. Analyses of labeled proteoglycans by glycerol density gradient centrifugation under dissociative conditions and by gel filtration showed that the major high molecular weight proteoglycan characteristic of cartilage was absent, but smaller proteoglycans were present in normal amounts. Antibodies directed against proteoglycan core protein failed to stain the cmd/cmd cartilage while antibodies to type II collagen stained the cartilage without hyaluronidase pretreatment. Addition of beta-D-xyloside, an exogenous substrate for chondroitin sulfate synthesis, and direct assay for beta-D-xylosyltransferase activity indicated that cmd/cmd cartilage cells contained normal levels of the enzymes required for chondroitin sulfate synthesis. The data suggest that cmd/cmd is defective in the synthesis of the cartilage proteoglycan core protein.

Animals↗

Magnetic resonance imaging of cartilage and cartilage repair.

Magnetic resonance (MR) imaging of articular cartilage has assumed increased importance because of the prevalence of cartilage injury and degeneration, as well as the development of new surgical and pharmacological techniques to treat damaged cartilage. This article will review relevant aspects of the structure and biochemistry of cartilage that are important for understanding MR imaging of cartilage, describe optimal MR pulse sequences for its evaluation, and review the role of experimental quantitative MR techniques. These MR aspects are applied to clinical scenarios, including traumatic chondral injury, osteoarthritis, inflammatory arthritis, and cartilage repair procedures.

Arthritis, Rheumatoid↗

Mineralization of normal and rachitic chick growth cartilage: vascular canals, cartilage calcification and osteogenesis.

This paper reviews recent work in the authors' laboratories that has led to new observations and thoughts concerning the mineralization of normal and rachitic chick growth cartilage. The proximal tibial growth cartilages of normal and rachitic chicks were rapidly frozen and prepared for SEM and biochemical studies. Using a scanning microfluorimetric technique we showed that at the mineralization front of normal and rachitic cartilage there is an abrupt change in chondrocyte metabolism. Thus cells in this region exhibited an increase in NADH and oxidative metabolism. In rickets, there was a decrease in the reduced pyridine nucleotide content of each of the zones. The reversal in chondrocyte metabolism was not due to low oxygen tension. SEM observations indicated that this region of cartilage was well supplied with vascular channels; moreover, mineral was first seen deposited in matrix in close proximity to the blood supply. Indeed these vascular channels appeared to be a basic architectural feature of normal cartilage, although disorganized in the rachitic state. The morphological studies also showed that gaps existed in the continuity of the mineral phase in normal cartilage. Although the rachitic cartilage does mineralize, discontinuities in the mineral distribution are much more severe, with the general failure of fusion of adjacent mineral clusters. These structures would serve as pathways for transport of nutritional factors and gases to chondrocytes that are distant from the vascular channels. Observation of hypertrophic cells reinforced the view that some osteoblasts represented a terminal stage in the maturation of chondrocytes.

Animals↗

Inhibition of calcium pyrophosphate dihydrate crystal formation in articular cartilage vesicles and cartilage by phosphocitrate.

Articular cartilage vesicles (ACV), isolated by differential centrifugation of adult hyaline articular cartilage collagenase digests, mineralized in the presence of calcium and ATP. Mineral analysis by microscopy, chemical analysis, energy-dispersive analysis, and infrared spectroscopy revealed crystals resembling calcium pyrophosphate dihydrate (CPPD). Adult articular cartilage also underwent ATP-dependent mineralization, supporting the contention that vesicles in situ fostered adult articular cartilage mineralization. Phosphocitrate (PC) is a recognized in vitro inhibitor of hydroxyapatite and calcium oxalate monohydrate crystal formation, but it is not known whether PC can similarly restrict CPPD crystal development. In the present study we examine the effect of PC, citrate, and n-sulfo-2-amino-tricarballylate (SAT, a PC analogue) on the ATP-induced CPPD crystal formation in both ACV and articular cartilage models. Only PC (10-1000 microM) blocked both the ATP-dependent and -independent mineralization in ACV in a dose-dependent fashion. At 1 mM, SAT and citrate blocked the ATP-independent mineralization. Similarly, only PC blocked both the ATP- and non-ATP-dependent mineralization in native articular cartilage slices. PC, SAT, and citrate had no effect on ACV nucleoside triphosphate pyrophosphohydrolase activity, suggesting that none of these agents blocked mineralization through the inhibition of nucleoside triphosphate pyrophosphohydrolase activity, which generates inorganic pyrophosphate from ATP.

Adenosine Triphosphate↗

A peek into the possible future of management of articular cartilage injuries: gene therapy and scaffolds for cartilage repair.

Two rapidly progressing areas of research will likely contribute to cartilage repair procedures in the foreseeable future: gene therapy and synthetic scaffolds. Gene therapy refers to the transfer of new genetic information to cells that contribute to the cartilage repair process. This approach allows for manipulation of cartilage repair at the cellular and molecular level. Scaffolds are the core technology for the next generation of autologous cartilage implantation procedures in which synthetic matrices are used in conjunction with chondrocytes. This approach can be improved further using bioreactor technologies to enhance the production of extracellular matrix proteins by chondrocytes seeded onto a scaffold. The resulting "neo-cartilage implant" matures within the bioreactor, and can then be used to fill cartilage defects.

Cartilage Diseases↗

Proteoglycan synthesis and content in articular cartilage and cartilage repair tissue in horses.

Hexosamine concentration, DNA concentration, and [35S]sulfate incorporation for articular cartilage obtained from various sites in the metacarpophalangeal and carpal joints of horses were measured. The same measurements were made on the repair tissue filling full-thickness articular defects in the intermediate carpal bone and on cartilage surrounding partial-thickness defects 6 weeks after the defects were created arthroscopically. Cellularity (measured as DNA concentration), proteoglycan content (measured as hexosamine concentration), and proteoglycan synthesis (measured as [35S]sulfate incorporation) varied according to the site sampled. Cartilage from the transverse ridge of the head of the third metacarpal bone and the radial facet of the third carpal bone had the lowest hexosamine concentration, whereas rate of proteoglycan synthesis was lowest in cartilage from the transverse ridge of the head of the third metacarpal bone and the distal articular surface of the radial carpal bone. Repair tissue filling a full-thickness cartilage defect at 6 weeks was highly cellular. It was low in proteoglycan content, but was actively synthesizing these macromolecules. In contrast, the cartilage surrounding a partial-thickness defect was unchanged 6 weeks after the original defect was made.

Animals↗

Growth behaviour of condylar cartilage and epiphyseal cartilage on the different medium of the organ culture.

In order to compare histological differences between the condylar and epiphyseal cartilages, an organ culture system was employed. Materials from 36 neonatal rabbits were cultured for 7 days on three different, chemically defined media (Ham F12, Medium 199, and Eagle's minimum essential medium) with the addition of various concentrations of ascorbic acid, fetal calf serum and NaHCO3. The epiphyseal cartilage was maintained in situ histological and biochemical features better than the condylar cartilage on any of the medium used. The maximum sensitivity to Toluidine Blue staining of the cultured condylar cartilage was observed on Ham F12. For both the condylar and epiphyseal cartilages, Ham F12 with the addition of 50 microgram/ml ascorbic acid and higher concentration of NaHCO3 was more effective on the maintenance of cell organization. However, effect of the addition of fetal calf serum to the medium was quite different between the condylar and epiphyseal cartilages, that is, the former showed better histological features without the addition, but the latter showed features similar to that in situ with 20% addition of fetal calf serum.

Animals↗