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[The early development of the articular cartilage. IV. The metamorphosing cartilage].

The definite articular cartilage originate from 2 anlagen, the primordial tangential layer and the greater part including the joint bone plate from the metamorphosing cartilage. The tangential layer grow by apposition from the perichondrium. Additional the layer becomes also dilatated as a result of the growing volume of the ossification center. In this way the Lamina splendens with residues of cells may be formed. The chondrocytes resemble partly fibroblasts, in older animals possibly even tendocytes. Moreover the cells exhibit a varying different shape. Today it is impossible to interpret the polymorphism of the cells. In the primordial state, the chondrocyts are embedded in a network from thin cartilage fibrils. Later on collagen fibrils from varied thickness (up to 900 A) are formed. The fibrils run only partly parallel to each other, in general they form a network, in which they cross with a low angle. There are great local differences in the fibrillar structure by the same animal.

Animals↗

[Preservation of articular cartilage. 2. Behavior of glycosaminoglycans (GAG) in the intracellular substance of preserved articular cartilage (histo- and biochemical studies)].

Glucosaminoglucanes (acid mucopolysaccharides) were assessed by means of histochemic and biochemic methods in differently preserved articular cartilages of adult Alsatian dogs. Immediately after lyophilization, resp. 14 days after preservation at --196 degrees C., the glucosaminoglucanes decrease, whereas they are present in undiminished concentration after deep-freezing preservation (--18 degrees C. and --78 degrees C.) up to 30 months, and at +4 degrees C. up to 100 days. No more destruction of glucosaminoglucanes occurs after dying of chondrocytes, obviously depending on blocking the glucosaminoglucanes destructing enzymes during the freezing. With regard to the investigations on the vitality, deep-freezing preservation at --18 degrees C. to --78 degrees C. is recommended for storage of avital articular cartilage. Preservation of vital articular cartilage is possible for 28 days at +4 C. in 5 per cent glucose solution.

Animals↗

Studies of nucleotides of growth-plate cartilage: evidence linking changes in cellular metabolism with cartilage calcification.

The objective of this study was to examine the nucleotides of chick growth-plate cartilage and to measure the concentration of adenine nucleotides in the pre-mineralizing and mineralizing zones. Nucleotides were isolated from the two regions using a rapid-freezing technique and the concentration of individual components was ascertained by HPLC. The actual values of ATP, ADP, and other nucleotides in cartilage was low. The lowest values were recorded in the mineralized zone. In this latter zone the energy charge ratio and the ATP/ADP ratio were depressed. This was probably due to 02-related inhibition of mitochondrial oxidative activity. Additionally, the percentage of octanoate, a short-chain fatty acid that accumulates when aerobic metabolism is disturbed, was found to have increased in the calcifying zone. These findings suggest that calcification of cartilage is associated with hypoxia-related modulation of chondrocyte metabolism.

Animals↗

Cartilage oligomeric matrix protein in serum and synovial fluid of rheumatoid arthritis: potential use as a marker for joint cartilage damage.

This study examined the serum and synovial fluid concentrations of cartilage oligomeric matrix protein (COMP) in relation to the evolution of joint cartilage damage and the requirement for surgery in 125 patients with rheumatoid arthritis (RA). We compared the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and matrix metalloproteinase-3 (MMP-3) levels with COMP levels determined by specific enzyme-linked immunosorbent assay (ELISA). Patients were divided into three groups: (1) patients with least erosive disease (LES); (2) patients with more erosive disease (MES); and (3) patients with mutilating disease (MUD). In addition, synovial fluid samples were collected from patients undergoing arthroscopic synovectomy of the knee joint (ASS) and total knee arthroplasty (TKA). Serum COMP levels correlated with the ESR (P < 0.0001, r = 0.374, n = 125) and the CRP level (P = 0.0014, r = 0.281, n = 125). COMP levels did not correlate with the MMP-3 level (P = 0.182, r = 0.114, n = 125). The COMP levels of the LES group were significantly lower than those of the MES or MUD groups. Lastly, synovial fluid COMP levels in the TKA group were higher than in the ASS group. Therefore, these findings suggest that serum and synovial fluid COMP levels in patients with RA may reflect cartilage destruction and are correlated with the ESR and the CRP level, which are indicators of the acute-phase response.

Journal Article↗

Abnormal collagen fibrillogenesis in epiphyseal cartilage of CMD (cartilage matrix deficiency) mouse.

Light and electron microscopic observations on the structure of epiphyseal cartilages in the cmd/cmd mice, which had genetically failed to synthesize cartilage-characteristic proteoglycan but were normal in type II collagen synthesis, showed apparent abnormalities of collagen fibrils: e.g. increase in the diameter, appearance of periodic banding patterns and bundle-formation of collagen fibrils. These findings suggest that cartilage-characteristic proteoglycan normally limits the lateral growth of collagen fibrils and affects collagen fibrillogenesis in vivo.

Animals↗

Culture and cryopreservation of chondrocytes from human cartilage: relevance for cartilage allografting in otolaryngology.

One of the reasons for failure of cartilage allografts is the impaired condition of the transplant during storage. In this paper we describe methods for the isolation and culture of viable chondrocytes obtained from nasal septum cartilage. Furthermore, we evaluate the possibility of growing such specific chondrocytes under culture conditions and storing them in a frozen state. Age-dependent differences were observed in the growth rate of the cultured cells. Our results confirm that chondrocytes survive freezing and remain able to proliferate. Knowledge gained from this study may be applied to the culture and freezing of viable intact cartilage for use in reconstructive surgery in otolaryngology.

Adolescent↗

Growth and development of the human cricoid cartilage: an immunohistochemical analysis of the maturation sequence of the chondrocytes and surrounding cartilage matrix.

OBJECTIVES: The goal was to determine maturational changes in the human cricoid cartilage. STUDY DESIGN: The study involved immunohistochemical staining of collagen II (a marker of proliferating chondrocytes), matrilin-1 (a marker of post-proliferative chondrocytes), and collagen X (a marker of hypertrophic chondrocytes). Specimens included uninjured human cricoid cartilages at 18 and 41 weeks' gestation and 1, 4, and 13 years postpartum. RESULTS: This study demonstrated that type II collagen peaks in concentration at approximately 41 weeks' gestation. Matrilin-1 is present in progressively lower concentration in the central core of the cricoid ring, but the peripheries of the ring contain the protein in relatively high concentration. Type X collagen is not expressed in the age groups tested. CONCLUSIONS: These biochemical markers lend further support to a chondrocyte proliferative phase that slows between 1 and 4 years of age. Chondrocytes then enter a phase histologically similar to the hypertrophic phase but are biochemically different than hypertrophic chondrocytes destined for endochondral ossification.

Adolescent↗

Proteoglycan metabolism in isolated chondrocytes from human cartilage and in short-term tissue-cultured human articular cartilage.

The effect of piroxicam on proteoglycan metabolism of human cartilage cells was investigated in two in vitro models. Cells or tissue samples were obtained from six different donors. Piroxicam levels used in the test systems ranged from 2 to 6 micrograms r/ml and were comparable with serum concentrations in humans after oral intake. Piroxicam increased the synthesis rates of proteoglycan in some batches of isolated and monolayer-cultured chondrocytes and in tissue-cultured articular cartilage. The fact that this increase in the synthesis of proteoglycan was restricted to some of the donors whereas isolated cells or tissue samples from other individuals remained unaffected illustrates the heterogeneity of different human donors. Depression of proteoglycan synthesis in the presence of the drug was not observed.

Cartilage↗

Treatment with calcitonin suppresses the responses of bone, cartilage, and synovium in the early stages of canine experimental osteoarthritis and significantly reduces the severity of the cartilage lesions.

OBJECTIVE: To relate the rate of bone resorption to serum levels of both hyaluronan (HA) and antigenic keratan sulfate (KS) in canine experimental osteoarthritis (OA) and to evaluate the effects of calcitonin on these parameters and the OA lesions of the unstable knee. METHODS: Twenty-two dogs underwent anterior cruciate ligament transection (ACLT) and 6 dogs underwent sham operation. Urinary pyridinium crosslinks were quantified by high-performance liquid chromatography. Immunoassays quantified hyaluronan (HA) and antigenic KS. Macroscopic and histologic OA lesions were scored. Calcitonin treatment was started on day 14 postsurgery and stopped on either day 49 or day 104 postsurgery. Control dogs and all treated dogs were killed on day 105. RESULTS: All ACLT joints developed OA. In contrast to sham-operated animals, all operated dogs exhibited an early and sustained rise in the levels of their urinary and serum markers. Calcitonin markedly reduced the levels of these markers and the severity of OA lesions. Furthermore, the longer the period of calcitonin therapy, the lower the score of the OA lesions. CONCLUSION: Bone, synovium, and articular cartilage all appear to be involved in the state of hypermetabolism that develops in unstable joints. Furthermore, the rate of bone resorption increases markedly in the early stages of this OA model and is likely to contribute to cartilage breakdown. Since calcitonin reduced the severity of OA changes, this form of therapy may have benefits for humans who have recently experienced a traumatic knee injury.

Amino Acids↗

In vitro synthesis of tissue-specific type II collagen by healing cartilage. I. Short-term repair of cartilage by mature rabbits.

The healing of surgically induced defects in mature rabbits' hyaline cartilage was examined histologically and biochemically. The subchondral bone underneath the lesion was the source of repair. At the end of the first month, mushroom-shaped chondroid buds were seen sprouting from the subchondral bone. By the tenth week, these buds fused to a cartilagenous plug filling the lesion. The repaired cartilage synthesized Type II collagen.

Aging↗

The use of angiostatic steroids to inhibit cartilage destruction in an in vivo model of granuloma-mediated cartilage degradation.

Angiogenesis is an important component of the development of chronic inflammatory diseases such as rheumatoid arthritis. It is known that clinically used anti-rheumatic drugs exert, in part, effects on the angiogenic response. Little work, however, has investigated the potential of experimental angiostatic therapies in chronic inflammatory disease models. The effect of one such angiostatic treatment, cortisone combined with heparin, was tested in an in vivo model of granuloma-mediated cartilage degradation. Angiostatic treatment significantly retarded the growth of granulomatous tissue, mononuclear cell influx into the granuloma, and the degradation of juxtaposed cartilage. This correlated with a decrease in the vascularity of the granulomatous tissue. Modulation of this component of pathogenesis of "angiogenesis-dependent disease" may be useful as a new therapeutic approach.

Animals↗

The cartilage-sparing versus the cartilage-cutting technique: a retrospective quality control comparison of the Francesconi and Converse otoplasties.

From a total of 281 patients with protruding ears who underwent a bilateral otoplasty between 1990 and 2001, a group of 28 (10%) was selected for a retrospective quality control study. The goal was to compare two methods of otoplasty, the Francesconi, a cartilage-sparing technique, and the Converse, a cartilage-cutting technique, in terms of objectively measurable and subjectively discernable differences in results. Objective parameters included measurement of the three cephaloauricular distances and the conchoscapal angle. An independent plastic surgeon performed the evaluation by means of a systematic evaluation system for rating cosmetic surgical procedures and a 5-point visual analog scale for rating satisfaction. The patients' subjective rate of satisfaction also was investigated using the 5-point scale. The mean medial and inferior cephaloauricular distances were significantly smaller in the Francesconi group. The concoscaphal angle was 90 degrees, or less in all the patients of the Francesconi group, but more than 90 degrees in eight patients (57%) of the Converse group (p = 0.041). Accordingly, the independent surgeon found adequate correction of protrusion in 86% of the Francesconi group and 50% of the Converse group (p = 0.050). His satisfaction rate was significantly in favor of the Francesconi technique (p = 0.006). Not unexpectedly, the patients' satisfaction rate was comparably high in both groups, and there was no statistical difference between them. In conclusion, the quality control led to a clear preference of the Francesconi over the Converse otoplasty. In addition, the assessment of the postoperative results with the systematic evaluation system offered an excellent information base by which to judge the results of otoplasty. Consequent use of this evaluation system will lead to progress in the surgical procedure.

Adolescent↗

Arthritic disease suppression and cartilage protection with glycosaminoglycan polypeptide complexes (Peptacans) derived from the cartilage extracellular matrix: a novel approach to therapy.

Molecular fragments of cartilage are antigenic and can stimulate an autoimmune response. Oral administration of type II collagen prevents disease onset in animal models of arthritis but the effects of other matrix components have not been reported. We evaluated glycosaminoglycan polypeptides (GAG-P) and matrix proteins (CaP) from cartilage for a) mitigating disease activity in rats with collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) and b) stimulating proteoglycan (PG) synthesis by chondrocytes in-vitro. CIA and AIA were established in Wistar rats using standard methods. Agents were administered orally (10-200 mg/kg), either for seven days prior to disease induction (toleragenic protocol), or continuously for 15 days after injecting the arthritigen (prophylactic protocol). Joint swelling and arthritis scores were determined on day 15. Histological sections of joint tissues were assessed post-necropsy. In chondrocyte cultures, CaP + / - interleukin-1 stimulated PG biosynthesis. CaP was also active in preventing arthritis onset at 3.3, 10 or 20 mg/kg in the rat CIA model using the toleragenic protocol. It was only active at 20 and 200 mg/kg in the CIA prophylactic protocol. GAG-P was active in the CIA toleragenic protocol at 20 mg/kg but chondroitin sulfate and glucosamine hydrochloride or glucosamine sulfate were all inactive. The efficacy of CaP in the rat AIA model was less than in the CIA model. These findings lead us to suggest that oral CaP could be used as a disease-modifying anti-arthritic drug.

Animals↗

Cartilage electromechanics--II. A continuum model of cartilage electrokinetics and correlation with experiments.

We have formulated a continuum model for linear electrokinetic transduction in cartilage. Expressions are derived for the streaming potential and streaming current induced by oscillatory, uniaxial confined compression of the tissue, as well as the mechanical stress generated by a current density or potential difference applied to the tissue. The experimentally observed streaming potential and current-generated stress response, measured on the same specimens, are compared with the predictions of the theory over a wide frequency range. The theory compares well with the data for reasonable values of cartilage intrinsic mechanical parameters and electrokinetic coupling coefficients. Experiments also show a linear relationship between the stimulus amplitude and the transduction response amplitude, within the range of stimulus amplitudes of interest. This observation is shown to be consistent with the predictions of the linear theory.

Animals↗

[Significance of immune reactions to cartilage tissue in use of cartilage transplants in nose surgery: detection of anti-collagen antibodies].

In a group of patients who showed repeated resorption or rejection of the transplanted cartilage graft, the immune response against a broad spectrum of collagen, namely, types I, II, VI, IX and XI, was investigated. We found a humoral immune reactivity against collagen type IX und XI, and to a lesser degree against collagen type I, demonstrating a specific immune response to these matrix collagens. These data suggest that some of the unsuccessful results obtained with cartilage grafts may be influenced by factors independent of the operative technique, such as immunological reactions.

Adult↗

The cellular origin of cartilage-like tissue after periosteal transplantation of full-thickness articular cartilage defects: an experimental study using transgenic rats expressing green fluorescent protein.

BACKGROUND: Periosteal transplantation is commonly used for the treatment of articular cartilage defects. However, the cellular origin of the regenerated tissue after periosteal transplantation has not been well defined. The objective of this study was to investigate the cellular origin of the regenerated tissue after periosteal transplantation. METHOD: Free periosteum was harvested from the tibia of 10-week-old adolescent enhanced green fluorescent protein (GFP-) expressing transgenic Sprague Dawley (SD) rats and was transplanted to full-thickness articular cartilage defects of the patellar groove in normal 10-week-old adolescent SD rats. The periosteum was sutured to the defect with the cambium layer facing the joint cavity. 8 SD rats were killed at 4 weeks and 8 SD rats were killed at 8 weeks after surgery. The repaired tissue was assessed histologically and histochemically. GFP-positive cells derived from the donor periosteum could easily be detected in the repaired tissue by use of a fluorescent microscope. RESULTS: At both 4 and 8 weeks after transplantation, the entire area of the defects had been repaired, with the regenerated tissue being well stained histologically with safranin-O. Most cells in the whole area of the regenerated tissue were GFP-positive, indicating that very few of the cells were GFP-negative cells originating from the recipient rats. INTERPRETATION: This experiment demonstrates that most cells in regenerated tissue after periosteal transplantation using adolescent animals do not originate from recipient cells but from the periosteal cells of the donor.

Animals↗

Cartilage oligomeric matrix protein: a novel marker of cartilage turnover detectable in synovial fluid and blood.

Cartilage oligomeric matrix protein (COMP) is a tissue specific non-collagenous matrix protein. We have developed an enzyme-linked immunosorbent assay for the detection of this protein in synovial fluid and serum. The protein has been quantified in these fluids in patients with rheumatoid arthritis (RA), reactive arthritis, juvenile chronic arthritis, osteoarthritis and in sera of control subjects. The protein was detectable in all fluids and the synovial fluid levels were always higher than in serum in paired samples. The highest knee joint synovial fluid levels were found in reactive arthritis patients and the lowest in RA patients with advanced destruction of the knee joint. However, the relative synovial fluid content of COMP was higher in these RA patients than in patients with advanced osteoarthritis. In patients with long-standing reactive synovitis the concentrations decreased. This decrease, however, was less marked than for proteoglycan concentrations. The serum concentrations were low in patients with juvenile chronic arthritis and in patients with RA with advanced cartilage destruction of the studied knee joint. In the other groups serum levels did not differ between groups or from controls.

Adult↗