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PubMed1995

Experimental and clinical study on the vitality of orthotopic cartilage transplants.

Orthotopic cartilage transplants are performed in the course of numerous rhinosurgical operations. Precondition of a permanent success of the operation is preservation of vitality of the transplanted cartilage. Although numerous study results of heterotopic cartilage transplants exist, corresponding examinations in orthotopic transplants have not been done so far. Therefore, in 33 rabbits we did a partial submucous septumresection and put the cartilage back between the mucosal wall. After 1, 2, 3, 6, and 12 weeks, the animals were killed and the cartilage histologically proved. These results were compared to analogous human biopsies. Cartilage reintegration showed a characteristic picture. In the rabbit, the replanted cartilage was healed and stable after 3 months in each case. During reintegration, appositional growth started from the inner perichondrium. With microangiographical examinations, we were able to demonstrate that the speed of reintegration increased with decreasing distance of the cartilage cell from the blood vessels. We managed to confirm the experimental results in human cartilage biopsies.

Animals↗
PubMed1999

Comparison of amounts and properties of collagen and proteoglycans in condylar, costal and nasal cartilages.

In this study we compared the compositions of extracellular matrices of condylar, costal and nasal cartilages to characterize differences in growth patterns in relation to matrix composition. Condylar, costal and nasal cartilages of 25- and 35-day-old rabbits were extracted and subjected to bio- and histochemical analysis to determine total amounts of collagen and amounts and aggregating properties of proteoglycans. We found that proteoglycan content and aggregate formation were greatest in nasal cartilage, and lower in costal and markedly lower in condylar cartilage. The amount of proteoglycans increased by varying amounts in all samples with age. Collagen content was highest in costal cartilage. In 25-day-old rabbits the quantity of collagen in condylar cartilage exceeded that in nasal cartilage. In 35-day-old rabbits the quantities were nearly the same. It is suggested that collagen does not only provide tensile strength, but counteracts forces responsible for interstitial growth such as osmotic pressure. Based on the results, it seems that the amount of proteoglycans is greater in cartilages, which have greater independent growth potential. Variations in increase in amount of proteoglycans with age could reflect differences in the timing of growth of such cartilages.

Animals↗
PubMedDate not supplied

Mechanisms of proteoglycan metabolism that lead to cartilage destruction in the pathogenesis of arthritis.

The mechanisms and agents involved in cartilage matrix destruction are poorly understood and at present there are no means of therapeutic intervention that halt or slow the degradative processes that result in tissue loss, joint space narrowing and the eventual need for surgery with total joint replacement. In recent years our laboratory has pioneered the development and use of monoclonal antibody (MAb) technologies for the study of changes in cartilage matrix metabolism in health and disease. In this chapter we have summarized results coming from our recent studies examining the mechanisms of cartilage proteoglycan (aggrecan) catabolism that precedes cartilage destruction in arthritis. This research has used two approaches. The first is our access to a panel of MAbs that recognize both constitutive structural epitopes and catabolic neoepitopes on cartilage proteoglycan metabolites. These antibodies have allowed us to determine whether the unknown proteolytic agent 'aggrecanase' or known matrix metalloproteinases (MMPs) are involved in the increased aggrecan catabolism that is observed in arthritis. Secondly, we have used reverse transcription-polymerase chain reaction (RT-PCR) techniques to profile the expression of members of the MMP family or ADAMs (A disintegrin and metalloproteinase) that are potentially involved in this degenerative process. Collectively, these investigations have established that aggrecanase is the major proteolytic activity responsible for aggrecan loss in the early stages that lead to cartilage degradation in arthritis. In addition, our studies have allowed us to determine many important biochemical properties of aggrecanase without knowing the identity of the enzyme. Our data also calls into question the role that MMPs may play in the early stages of cartilage destruction that lead to surface fibrillation. However, MMPs may be involved in later stages where collagen degradation is prevalent. The role that ADAMs play is still unknown, although they are postulated to play an important role in shedding or activation of different classes of matrix proteases. Furthermore, we have observed changes in the patterns of cartilage expression in fresh tissue and model culture systems. This work has indicated clearly that there are several different classes of enzyme that can be targeted for innovative therapies which could slow or halt cartilage destruction in arthritis.

Journal Article↗
PubMed1992

Immunohistochemical localization of basal lamina components in the developing rat epiphyseal cartilage canals.

The purpose of this study was to investigate the relationship between the appearance of basal lamina components (Type IV collagen and laminin) and the development of cartilage canals. In the distal femoral epiphyses from developing rats, the distribution of basal lamina components in the cartilage canal was examined immunohistochemically. The formation of cartilage canals from the perichondrium was first observed on the fifth day after birth. By Day 8, a few cartilage canals penetrated the epiphyseal cartilage and considerably increased in size and length. By light microscopic immunohistochemistry, reticular structures stained with anti-Type IV collagen and antilaminin antibodies were observed in the cartilage canals. In the early development of cartilage canals, however, immunostaining by anti-Type IV collagen antibodies was weaker than that by antilaminin antibodies. In eight-day-old rats, the laminin-positive reticular structures were more densely colored and more widely distributed in the canal than the Type IV collagen-positive ones. Type IV collagen was found around the endothelial cells of the developing capillaries by electron microscopic immunohistochemistry. Laminin was observed in the cytoplasm of the mesenchymal fibroblastic cells and their pericellular matrix as well as in the capillary basal lamina. These immunohistochemical electron microscopic observations can explain the differences that are observed in Type IV collagen and laminin immunostaining patterns as cartilage canals develop. Laminin synthesized by the mesenchymal fibroblastic cells may promote the migration and the outgrowth of endothelial cells in the formation of cartilage canals.

Animals↗
PubMedDate not supplied

Dorsal onlay cartilage autografts: comparing resorption in a rabbit model.

OBJECTIVE: To compare the resorption characteristics of dorsal onlay cartilage autografts from the septum, auricle, and rib. METHODS: Fourteen New Zealand white rabbits underwent harvesting of equal-sized septal, auricular, and costal cartilage grafts free of perichondrium. All autografts were implanted subcutaneously on the nasal dorsum and then removed after 3 months. Graft mass, chondrocyte density, and histologic features from hematoxylin-eosin-stained sections were compared before and 3 months after implantation. RESULTS: At 3 months after implantation, septal cartilage grafts averaged 30.8% resorption by weight, followed by auricular (23.1%) and costal (7.6%) cartilage. All 3 groups demonstrated similar changes in chondrocyte density and minor calcification at 3 months. There was no evidence of necrosis or inflammatory changes in any of the specimens. CONCLUSIONS: Although the septum is often the preferred source of autogenous cartilage for nasal reconstruction, short-term resorption of septal cartilage appears to be higher for dorsal onlay grafts. The low resorption of costal cartilage may be due in part to its compact shape compared with septal and auricular cartilage. It remains to be seen whether these differences in resorption persist in the long term.

Animals↗
PubMed2004

Tissue-engineered cartilage as a graft source for laryngotracheal reconstruction: a pig model.

OBJECTIVE: To evaluate the feasibility of using tissue-engineered cartilage for laryngotracheal reconstruction in the pig model. DESIGN: Auricular cartilage was harvested from 3 young swine. The cartilage was digested, processed, and suspended and a cell culture was obtained. The cells were then suspended in 3 mL of a 30% solution of a biodegradable polymer (Pluronic F-127) (polyethylene oxide/polypropylene oxide copolymer) at a cellular concentration of 50 x 10(6) cells/mL. This suspension was then implanted subcutaneously into each pig's dorsum. Eight weeks after implantation, the cartilage was harvested with the surrounding perichondrial capsule. An anterior cartilage graft laryngotracheal reconstruction was performed. Bronchoscopy was performed at 3 postoperative weeks to demonstrate airway patency. The animals were killed at 3 months, and specimens were obtained for histological analysis. SETTING: An animal research facility. SUBJECTS: Three young Yorkshire swine. RESULTS: All 3 pigs survived to the 3-month postoperative interval with no evidence of stridor or airway distress. Interval bronchoscopy revealed a normal patent airway with a mucosalized graft. Histopathologic analysis revealed incorporation of the tissue-engineered cartilage graft in the cricoid area, which correlated with results of bronchoscopic evaluation. CONCLUSION: Tissue-engineered auricular cartilage served as a viable graft in the pig model and might be an alternative cartilage source for laryngotracheal reconstruction.

Animals↗
PubMed1993

Inflammation-induced cartilage degradation in female rodents. Protective role of sex hormones.

OBJECTIVE: To investigate the effects of physiologic levels of sex steroids on inflammation and cytokine production and their consequential cartilage degradation. METHODS: We used an in vivo model of inflammation-induced cartilage degradation in female mice to study the effects of ovariectomy and hormone treatment, and in vitro culture systems to examine the influence of sex steroids on cartilage metabolism, interleukin-1 (IL-1) production by granulomatous tissue, and its effects on female mouse articular cartilage. RESULTS: Ovariectomy resulted in accelerated cartilage breakdown associated with increased production of IL-1 by granulomatous tissue. The effects of ovariectomy on cartilage were reversed by treatment with estradiol and androgen, but not by progesterone treatment. Estradiol and progesterone reduced both spontaneous and IL-1-induced cartilage degradation in vitro. Testosterone antagonized the effects of IL-1 on both proteoglycan loss and proteoglycan synthesis. CONCLUSION: These data suggest that sex steroids have an important influence on inflammation-induced cartilage breakdown in female animals, with protective effects of both estradiol and androgens. Multiple mechanisms may be involved, and they are likely to include direct immunomodulatory effects as well as interactions with the effects of cytokine and of the glucocorticoid response to inflammation.

Animals↗
PubMed1994

Localization of the expression of type I, II and III collagen genes in human normal and hypochondrogenesis cartilage canals.

The expression of type I, II and III collagens genes was examined in human normal and hypochondrogenesis cartilage canals employing electrophoretic analysis, immunohistochemistry and in situ hybridization techniques. In normal cartilage, collagens type I and III were present in perichondrium, in the connective tissue surrounding the vessels of cartilage canals and in the dense fibrous tissue. However, types I and III procollagen mRNAs were detected only in fibroblasts of the perichondrium and of the canals, but not in the polymorphic cells. Type II collagen was present in the cartilage matrix and in the dense fibrous tissue, in good accordance with the localization of type II procollagen mRNAs detected in the chondrocytes and in the polymorphic cells. These data suggest that there are no transitional cells expressing type I, II and III collagen genes and that polymorphic cells are of chondrocytic origin. In the case of hypochondrogenesis, type II collagen was less abundant than in normal cartilage, whereas the corresponding mRNA level was equivalent. That suggests that a postranscriptional regulation of this protein is involved in the decrease of type II collagen production. Type I collagen, unexpectedly detected in the cartilage matrix, was synthesized by chondrocytes and polymorphic cells, suggesting a replacement of type II by type I collagen. The canal hypertrophy observed in this pathological case could thus be due to a modification in the regulation of the growth of cartilage canals caused by a defective cartilage matrix.

Cartilage↗
PubMed1999

Osteogenic protein-1 (OP-1) blocks cartilage damage caused by fibronectin fragments and promotes repair by enhancing proteoglycan synthesis.

OBJECTIVE AND DESIGN: The abilities of osteogenic protein-1 (OP-1) and TGF-beta1 to affect cartilage damage caused by fibronectin fragments (Fn-fs) that are known to greatly enhance cartilage proteoglycan (PG) degradation were compared. MATERIAL: Articular cartilage was obtained from 18 month old bovines. TREATMENT: To test blocking of damage, cartilage was cultured with or without OP-1 or TGF-beta in the presence of 100 nM Fn-fs. To test restoration of PG, cartilage was first cultured with Fn-fs and the cartilage then treated with factors. METHODS: Cartilage PG content was measured in papain digests using the dimethylmethylene blue assay. PG synthesis was measured by incorporation of 35S labeled sulfate. RESULTS: OP-1 blocked damage and restored PG in damaged cartilage, apparently due to enhanced PG synthesis. However, TGF-beta1 alone decreased PG content. CONCLUSIONS: These results clearly demonstrate differences between OP-1 and TGF-beta1, both members of the TGF-beta superfamily and illustrate the efficacy of OP- in blocking Fn-f mediated damage.

Animals↗
PubMed2005

Comparison of multislice CT arthrography and MR arthrography for the detection of articular cartilage lesions of the elbow.

The objective of this study was to compare the value of multislice CT arthrography and MR arthrography in the assessment of cartilage lesions of the elbow joint. Twenty-six cadaveric elbow specimens were examined with the use of CT arthrography and MR arthrography prior to joint exploration and macroscopic inspection of articular cartilage. Findings at CT and MR arthrography were compared with macroscopic assessments in 104 cartilage areas. At macroscopic inspection, 45 cartilage lesions (six grade 2 lesions, 25 grade 3 lesions, 14 grade 4 lesions) and 59 areas of normal articular cartilage were observed. With macroscopic assessment as the gold standard CT and MR arthrography showed an overall sensitivity/specificity of 80/93% and 78/95% for the detection of cartilage lesions, respectively. Only two of six grade 2 lesions were detected by CT and MR arthrography. For the diagnosis of grade 3 and 4 lesions, the sensitivity/specificity was 87/94% with CT arthrography, and 85/95% with MR arthrography. In an experimental setting multislice CT arthrography and MR arthrography showed a similar performance in the detection of cartilage lesions. Both methods indicated limited value in the diagnosis of grade 2 articular cartilage lesions.

Aged↗
PubMed2006

Cartilage imaging: motivation, techniques, current and future significance.

Cartilage repair techniques and pharmacological therapies are currently areas of major clinical interest and research, in particular to prevent and treat osteoarthritis. MR imaging-based techniques to visualize cartilage are prerequisites to guide and monitor these therapies. In this review article, standard MR imaging sequences are described, including proton density-weighted fast spin echo, spoiled gradient echo and dual echo steady state sequences. In addition, new sequences that have been developed and are currently being investigated are presented, including driven equilibrium Fourier transform and steady-state free precession-based imaging. Using high-field MR imaging at 3.0-T, visualization of cartilage and the related pathology has been improved. Volumetric quantitative cartilage MR imaging was developed as a tool to monitor the progression of osteoarthritis and to evaluate new pharmacological cartilage protective therapies. The most exciting developments, however, are in the field of cartilage matrix assessment with quantitative dGEMRIC, T2 and T1rho mapping techniques. These techniques aim at detecting cartilage damage at a stage when changes are potentially still reversible, before cartilage tissue is lost. There is currently substantial interest in these techniques from rheumatologists and orthopedists; radiologists therefore need to keep up with these developments.

Cartilage Diseases↗
PubMed2004

Magnetic resonance evaluation of the interrelationship between articular cartilage and trabecular bone of the osteoarthritic knee.

OBJECTIVE: To use high-resolution magnetic resonance imaging (MRI) to determine the relationship between articular cartilage degeneration and trabecular bone changes of the femur, condyles and tibia in human knees with osteoarthritis (OA). METHODS: Subjects were divided into three groups: without OA (OA0), mild OA (OA1) and severe OA (OA2). Sagittal images of the knee (0.234 x 0.234mm2, 2-mm slice thickness) were obtained at 1.5T and used for calculating the volume and thickness of the femoral and tibial cartilage. Axial images (0.195 x 0.195mm2, 1-mm slice thickness) were used for calculating the trabecular bone structure parameters: apparent bone volume fraction, trabecular number, trabecular separation and trabecular thickness. RESULTS: Cartilage volume and thickness were less in patients with OA compared to normal controls (P<0.1). Articular cartilage thinning is associated with bone structure loss in the opposite femoral condyle (P<0.05). In varus OA, there were extensive correlations between medial tibia and medial femoral cartilage degeneration, and loss of bone structure in the lateral tibia and lateral condyle. Additional correlations existed between the compartmental differences (lateral minus medial) of cartilage thickness and bone structure. CONCLUSION: Degradation of articular cartilage within a compartment correlates with a loss of bone structure in the opposite compartment. The correlation between the (L-M) differences corroborates this relationship. Malalignment of the knee due to cartilage degeneration is associated with bone formation in the diseased condyle and bone resorption in the opposite compartment.

Age Factors↗
PubMed2004

Cartilage mechanics in the guinea pig model of osteoarthritis studied with an osmotic loading method.

OBJECTIVE: To determine the material properties of articular cartilage in the Hartley guinea pig model of spontaneous osteoarthritis. METHODS: Cartilage-bone samples from the medial femoral condyle and tibial plateau of 12 month-old guinea pig knees were subjected to osmotic loading. Site-matched swelling strains and fixed charge density values were used in a triphasic theoretical model for cartilage swelling to determine the modulus of the cartilage solid matrix. The degree of cartilage degeneration was assessed in adjacent tissue sections using a semi-quantitative histological grading scheme. RESULTS: Decreased values for both moduli and surface zone fixed charge density were associated with increasing grades of cartilage degeneration. Decreases in moduli reflect damage to the collagen matrix, which give rise to greater swelling strains. CONCLUSION: Histological evidence of cartilage degeneration was associated with impaired cartilage mechanics in the aging Hartley guinea pig.

Animals↗
PubMed2006

Microfracture and bone morphogenetic protein 7 (BMP-7) synergistically stimulate articular cartilage repair.

OBJECTIVE: Microfracture is used to treat articular cartilage injuries, but leads to the formation of fibrocartilage rather than native hyaline articular cartilage. Since bone morphogenetic protein 7 (BMP-7) induces cartilage differentiation, we hypothesized that the addition of the morphogen would improve the repair tissue generated by microfracture. We determined the effects of these two treatments alone and in combination on the quality and quantity of repair tissue formed in a model of full-thickness articular cartilage injury in adolescent rabbits. DESIGN: Full-thickness defects were made in the articular cartilage of the patellar grooves of forty, 15-week-old rabbits. Eight animals were then assigned to (1) no further treatment (control), (2) microfracture, (3) BMP-7, (4) microfracture with BMP-7 in a collagen sponge (combination treatment), and (5) microfracture with a collagen sponge. Animals were sacrificed after 24 weeks at 39 weeks of age. The extent of healing was quantitated by determining the thickness and the surface area of the repair tissue. The quality of the repair tissue was determined by grading specimens using the International Cartilage Repair Society Visual Histological Assessment Scale. RESULTS: Compared to controls, BMP-7 alone increased the amount of repair tissue without affecting the quality of repair tissue. Microfracture improved both the quantity and surface smoothness of repair tissue. Compared to either single treatment, the combination of microfracture and BMP-7 increased both the quality and quantity of repair tissue. CONCLUSIONS: Microfracture and BMP-7 act synergistically to stimulate cartilage repair, leading to larger amounts of repair tissue that more closely resembles native hyaline articular cartilage.

Animals↗
PubMed2005

Contrast-enhanced high-resolution magnetic resonance imaging of autologous cartilage implants of the knee joint.

Over the past decade, a number of interventions for durable cartilage repair have emerged. Magnetic resonance (MR) tomography is an excellent noninvasive method for monitoring cartilage repair tissues throughout the postsurgical period. However, evaluating cartilage morphology after matrix-based autologous cartilage implantation (ACI) with MR imaging (MRI) still remains a challenge. In this study, we combined a high-resolution cartilage-sensitive fast-spin echo (FSE) sequence with intravenous application of a contrast agent for enhancing synovial fluid. Two independent musculoskeletal radiologists interpreted the pictures for the thickness, length and surface of the cartilage implants. A multivariate two-way analysis of variance with two repeated measures was performed and showed that evaluation of cartilage implant morphology was significantly improved after the application of gadodiamide on proton density FSE images. Contrast-enhanced MRI of articular cartilages is a promising technique in the postoperative follow-up of patients after ACI.

Adult↗
PubMed2003

A role for the interleukin-1 receptor in the pathway linking static mechanical compression to decreased proteoglycan synthesis in surface articular cartilage.

Loading of articular cartilage during weight bearing is essential for the maintenance of cartilage function. Although certain cyclic loading protocols stimulate extracellular matrix synthesis, constant or static compression decreases proteoglycan and collagen synthesis in cartilage explants. The goal of this study was to determine whether the compression-induced decrease in proteoglycan synthesis involves an interleukin-1 (IL-1) signaling pathway. Cartilage explants were compressed 50% in the presence of IL-1 receptor antagonist (IL-1ra), and the incorporation of [35S]sulfate into macromolecules was measured. IL-1ra increased sulfate incorporation in compressed cartilage but not in cartilage maintained at the in situ thickness (0% compression). IL-1alpha and IL-1beta mRNAs were detected in cartilage compressed 50% for at least 3h, while nitric oxide synthase II mRNA was only detected in cartilage compressed 50% for 6h. The data support a role for the IL-1 receptor in the pathway linking static compression to reduced proteoglycan synthesis.

Animals↗
PubMed2003

Approach to cartilage injury in the anterior cruciate ligament-deficient knee.

The treatment of articular cartilage lesions remains one of the great challenges facing orthopedic surgeons today. The technique of chondrocyte transplantation has opened the door for the application of biologic solutions to difficult problems. These techniques will prove the keystone of further advances into biologic joint repair and replacement. Enthusiasm, however, must be tempered by the numerous gaps in cartilage science and the overwhelming need for further long-term data to demonstrate the efficacy of these techniques in thwarting the presumed eventual progression of these lesions toward osteoarthritis. The status of the articular cartilage is of paramount importance in ACL decision-making. Every effort must be made to protect the existing hyaline articular cartilage during ACL reconstruction. Though current cartilage repair techniques are in their infancy, they remain stepping-stones to future developments. It is hoped that we will one day be able to regenerate normal hyaline cartilage without great morbidity. At present, the ACL surgeon must accept techniques that diminish symptoms and do not burn bridges to future advances. The orthopedic surgeon must increase his knowledge of the basic science of articular cartilage in order to best choose from the various cartilage treatments that evolve.

Anterior Cruciate Ligament↗
PubMed1996

Histologic evaluation of auricular cartilage grafts after discectomy in the rabbit craniomandibular joint.

PURPOSE: The clinical use of auricular cartilage grafting after discectomy has been reported as a treatment in the terminal stage of internal derangement of the temporomandibular joint (TMJ). Although the occurrence of fibrous adhesions has been observed in such grafted joints, the exact tissue reaction to the graft is still not understood. The purpose of this study was to evaluate the histologic changes after discectomy and auricular cartilage grafting in the rabbit craniomandibular joint (CMJ). MATERIALS AND METHODS: Unilateral discectomy of the left CMJ was performed in 28 Japanese white rabbits. Auricular cartilage harvested from the ipsilateral ear was grafted as a disc replacement in 14 animals (Group C), and the other 14 underwent wound closure immediately after discectomy (Group B). Two other rabbits (Group A) served as nonsurgically treated controls. Two rabbits from each experimental group were killed at 2, 4, 6, 8, 10, 12, and 24 weeks postoperatively. Microscopic observation of the specimens was performed in the parasaggital plane. RESULTS: Complete resorption of the cartilage layer on the articular surface was observed within 4 weeks postoperatively in group B. Regeneration of a fibrous cartilage layer was observed in this group after 6 weeks, but the postoperative degenerative changes were so severe that the surface of the condyle and eminence was flattened. In contrast, the degenerative changes were milder in group C, although the grafted cartilage showed perforation and fragmentation from the sixth postoperative week onward. The condylar shape and cartilage layer were well preserved at all times. CONCLUSIONS: These results suggest that the structure and function of the condyle may be preserved by auricular cartilage grafting after discectomy. However, the problems of adhesion and fragmentation need to be addressed.

Animals↗