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The effect of tibial lengthening on immature articular cartilage of the knee joint.

OBJECTIVE: To investigate the acute response of immature articular cartilage, in the distraction and consolidation phases, to 30% tibial lengthening. DESIGN: Sixteen immature New Zealand white rabbits underwent diaphyseal lengthening of the left tibia by callotasis at a distraction rate of 0.4mm twice daily. A sham control group of 12 rabbits underwent fixation and osteotomy without lengthening. In each group, half of the rabbits were killed at the end of the distraction phase or at an equivalent time period and the rest were killed after an additional 5 weeks (consolidation phase). The tibial condyles and synovial fluid in the knee joint cavity were taken for laboratory examination. Sulfated glycosaminoglycan in synovial fluid was estimated using a colorimetric method. Sections along the mid-coronal plane of the whole of the tibial condyles were examined histologically and by scanning electron microscopy. A grading system was used to make a semiquantitative assessment of the histopathological changes in articular cartilage. RESULTS: Damage to the immature articular cartilage had occurred by the end of the distraction period and the cartilage continued to deteriorate in the consolidation phase of 5 weeks. However, when compared with a similar study in a mature rabbit model, damage to immature cartilage appeared less severe. CONCLUSION: This model of 30% lengthening caused acute cartilage damage which did not recover in the short term. The result may have implications for longer lengthening in children; the effects may be disadvantageous and lead to degenerative diseases later in life.

Animals↗

Macromolecular transport across the superficial layer of articular cartilage.

OBJECTIVE: To study the role of the superficial layer of articular cartilage in the transport of macromolecular solutes. DESIGN: The articular cartilage of intact bovine carpal bones was incubated with(125)I-labeled bovine serum albumin, human IgG, or horse ferritin for 4 hours. Quadruplicate samples were first incubated with polymorphonuclear neutrophil elastase for 30 minutes to remove the outermost layer covering the articular surface. The rates of exchange of each macromolecule from excised tissue explants in the absence of a concentration gradient were measured at six different time points. The results were expressed as the fraction of radioactive protein exiting the cartilage per mm(2)of tissue, or as picomoles of labeled solute per mm(2). RESULTS: Exchange rates correlated well with molecular mass, and no apparent differences were detected between intact and elastase-treated tissues. However, when the results were expressed in terms of the total number of molecules within the tissue, it was apparent that IgG molecules accumulated in the intact cartilage in larger than expected numbers. This finding was not observed in experiments using elastase-treated tissue. CONCLUSION: These observations suggest that the outermost surface layer does not constitute a barrier to the transport of macromolecules into the deeper zones of the tissue. The higher IgG accumulation observed in intact cartilage suggests that the acidic outer layer of cartilage exhibited attractive interactions, probably ionic in nature, with the cationic fraction of IgG. These observations may relate to our previous work demonstrating that the sequestered immune complexes in the superficial zone of articular cartilage in rheumatoid arthritis, and in the antigen-induced arthritis model, are formed because pre-existing antibody normally present in cartilage irreversibly traps antigen within the tissue.

Animals↗

The use of a novel PLGA fiber/collagen composite web as a scaffold for engineering of articular cartilage tissue with adjustable thickness.

It has been a great challenge to make the thickness of engineered cartilage adjustable to cover the range of both partial-thickness and full-thickness articular cartilage defects. We developed a novel kind of composite web scaffold that could be used for tissue enginnering of articular cartilage with the thickness adjustable between 200 microm and 8 mm. The composite web showed a unique structure having web-like collagen microsponges formed in the openings of a mechanically strong knitted mesh of poly(lactic-co-glycolic acid). The knitted mesh served as a skeleton reinforcing the composite web, while the web-like collagen microsponges facilitated cell seeding, cell distribution, and tissue formation. Bovine chondrocytes cultured in the composite web showed a spatially even distribution, maintained their natural morphology, and produced cartilaginous extracellular matrices such as type II collagen and aggrecan. The thickness of the implant can be simply adjusted by laminating or rolling the web sheets. Not only did the histological structure of the engineered cartilage patches match the bovine native articular cartilage, but also their dynamic complex modulus, structural stiffness, and phase lag reached 37.8, 57.0, and 86.3% of those of native bovine articular cartilage, respectively. The composite web could be an important scaffold for tissue engineering.

Aggrecans↗

Correlation between radiographic findings of osteoarthritis and arthroscopic findings of articular cartilage degeneration within the patellofemoral joint.

OBJECTIVES: To correlate radiographic findings of osteoarthritis on axial knee radiographs with arthroscopic findings of articular cartilage degeneration within the patellofemoral joint in patients with chronic knee pain. SUBJECTS AND METHODS: The study group consisted of 104 patients with osteoarthritis of the patellofemoral joint and 30 patients of similar age with no osteoarthritis of the patellofemoral joint. All patients in the study group had an axial radiograph of the knee performed prior to arthroscopic knee surgery. At the time of arthroscopy, each articular surface of the patellofemoral joint was graded using the Noyes classification system. Two radiologists retrospectively reviewed the knee radiographs to determine the presence of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts. The sensitivity and specificity of the various radiographic features of osteoarthritis for the detection of articular cartilage degeneration within the patellofemoral joint were determined. RESULTS: The sensitivity of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts for the detection of articular cartilage degeneration within the patellofemoral joint was 73%, 37%, 4%, and 0% respectively. The specificity of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts for the detection of articular cartilage degeneration within the patellofemoral joint was 67%, 90%, 100%, and 100% respectively. CONCLUSION: Marginal osteophytes were the most sensitive radiographic feature for the detection of articular cartilage degeneration within the patellofemoral joint. Joint-space narrowing, subchondral sclerosis, and subchondral cysts were insensitive radiographic features of osteoarthritis, and rarely occurred in the absence of associated osteophyte formation.

Adult↗

Advances in articular cartilage repair.

Many joint and systemic disorders may lead to cartilage defects. Partial thickness defects of the articular cartilage do not have healing potential. When the lesion reaches the subchondral bone, spontaneous healing may be observed, but consists of fibrocartilaginous tissue. The main efforts for cartilage repair are targeted at filling of the cartilage defect with a tissue that possesses the same mechanical properties with hyaline cartilage and the consolidation of this tissue with the native articular cartilage. There are various arthroscopic techniques and although they provide pain relief, they do not restore the damaged cartilage. Osteochondral transplantation is more effective in dealing with small or medium size full thickness defects, but further efforts are required in order to reduce the donor site morbidity, marginal necrosis and partial covering of the defect.

Arthroscopy↗

Frictional response of bovine articular cartilage under creep loading following proteoglycan digestion with chondroitinase ABC.

The specific aim of this study was to investigate the effect of chondroitinase ABC treatment on the frictional response of bovine articular cartilage against glass, under creep loading. The hypothesis is that chondroitinase ABC treatment increases the friction coefficient of bovine articular cartilage under creep. Articular cartilage samples (n = 12) harvested from two bovine knee joints (1-3 months old) were divided into a control group (intact specimens) and a treated group (chondroitinase ABC digestion), and tested in unconfined compression with simultaneous continuous sliding (+/- 4 mm at 1 mm/s) under a constant applied stress of 0.5 MPa, for 2500 s. The time-dependent response of the friction coefficient was measured. With increasing duration of loading, treated samples exhibited a significantly higher friction coefficient than control samples as assessed by the equilibrium value (treated: micro(eq) = 0.19 +/- 0.02; control: micro(eq) = 0.12 +/- 0.03; p = 0.002), though the coefficient achieved immediately upon loading did not increase significantly (treated: micro(min) = 0.0053 +/- 0.0025; control: micro(min) = 0.037 +/- 0.0013; p = 0.19). Our results demonstrate that removal of the cartilage glycosaminoglycans using chondroitinase ABC significantly increases the overall time-dependent friction coefficient of articular cartilage. These findings strengthen the motivation for developing chondroprotective strategies by increasing cartilage chondroitin sulfate content in osteoarthritic joints.

Animals↗

Concomitant meniscal and articular cartilage lesions in the femorotibial joint.

The frequency of concomitant meniscal and articular cartilage lesions in the femorotibial joint was analyzed in a retrospective study of 1740 knee joints examined arthroscopically with the objective of determining possible correlations between the two knee joint abnormalities. Articular cartilage lesions were found in 81.4% (N = 1416) of femorotibial joints examined and meniscal derangements were noted in 72.8% (N = 1268). In the medial compartment, concomitance was noted in 76.3% (821 of 1076) on the femoral condyles and in 48.6% (523 of 1076) on the tibial plateau. In the lateral compartment, 43.1% (212 of 492) of the knees with deranged menisci had femoral and 55.1% (271 of 492) had tibial articular lesions. Medial meniscal lesions were more frequently associated with femoral and tibial chondral degeneration than lateral meniscal derangements (P < 0.001). Longitudinal, bucket-handle, and complex tears of the medial meniscus were significantly more often associated with articular cartilage damage than horizontal cleavage, flap, or radial tears. Degeneration of the meniscus was highly correlated with chondral destruction in both compartments. No cause-and-effect relationship could be established, but practical implications of these findings are discussed.

Adolescent↗

[A study on abnormal chondrocyte differentiation and abnormal expression of collagen types in articular cartilage from patients with Kaschin-Beck disease].

OBJECTIVE: To study the abnormal characteristics of chondrocyte differentiation and abnormal expression of collagen types in articular cartilage from patients with Kaschin kaschin-Beck disease (KBD). METHODS: The abnormal differentiation and expression of collagen types I, II, III, IV and X in articular cartilage from five cases of KBD patients were examined using monoclonal immunohistochemical methods. RESULTS: (1) The expression of tyep II collagen was decreased in the upper zone in KBD articular cartilage. (2) The expression of types I, III and VI collagen were found throughout the articular cartilage, but type X collagen was located in the calcified cartilage zone and around chondrocyte clusters in the deep zone. (3) Chondrocyte clusters exhibited significant pericellular staining for types I, II, III and VI collagen, but did not stain with any collagen antibody in the chondronecrosis areas. CONCLUSION: The abnormal collagen pattern in the articular cartilage of KBD patients was similar to that seen in primary osteoarthritic cartilage, but having more pronounced type I collagen expression in the surface zone and no collagen expression in the chondronecrosis areas.

Adult↗

[Ultrastructural changes in articular cartilage in rheumatoid arthritis].

Electron microscope studies of the articular cartilages removed in the course of the operation on 6 patients with rheumatoid arthritis were carried out. The processes of destruction of chondrocytes and the cartilaginous matrix in different regions of the articular cartilage were traced. In the surface areas of the drastically changed cartilage there were observed leucocytes of the synovial fluid, and in deeper areas--disintegration of chondrocytes and extracellular disposition of lysosomes and altered organellas, destroyed cartilaginous cells. In these areas destruction of collagenous fibres was particularly intensive. In areas of the tissue remote from the destuction hypertrophy of chondrocytes due to hyperplasia of various organellas and the Golgi complex in particular were noted. In the Golgi zone granules of glycogen were detected. No mitoses were observed. Apparently, the enzymatic destruction of the cartilaginous matrix in rheumatoid arthritis could proceed at the expense of the activazation of the synovial fluid lysosomes and lysosomes of chondrocytes themselves. A reparative regeneration of the disintegrating matrix was realized mainly because of hypertrophy of the functionally preserved chondrocytes.

Arthritis, Rheumatoid↗

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 studies and osteoarthrosis.

Osteoarthrosis is characterized in the early stages by degradation of articular cartilage matrix. Clinical, radiological, and pathological studies have failed to reveal the factors which initiate the breakdown of cartilage and are not applicable to detailed sequential studies of the affected tissues at all stages in the disease. Therefore animal experiments have been employed to provide more information on degradation and repair process in cartilage. These studies have demonstrated: 1) Matrix protection and induced repair of mature articular cartilage by the use of oral aspirin after lacerative injury. 2) Establishment by the intra-articular injection of the plant enzyme papain of a model of osteoarthrosis in the rabbit hip which mimics human osteoarthrosis and is suitable for further experimental studies. 3) A proliferation of mature articular cartilage chondrocytes in response to loss of matrix, which indicates a latent repair capacity. 4) Repair of extensively damaged hip joints after femoral osteotomy by increased formation of subchondral new bone and formation of fibrocartilage on the articulating surfaces. These tissue repair processes are associated with an increase in vascularity of the femoral head and acetabulum produced by the osteotomy. 5) Succesful transplantation as allografts in both normal and arthrotic rabbit knees of aggregates of epiphysial chondrocytes isolated from their matrix. This method of joint surface replacement may have clinical applications.

Animals↗

Articular cartilage lesions in 993 consecutive knee arthroscopies.

BACKGROUND: Traumatic articular cartilage injuries heal poorly and may lead to development of osteoarthritis at a young age. This study estimates the number of patients who may benefit from one of the surgical methods of cartilage repair. METHODS: All patients undergoing knee arthroscopy during a 6-month period at three collaborating hospitals were consecutively evaluated according to the International Cartilage Repair Society (ICRS) knee form. The material consists of 993 consecutive knee arthroscopies in patients with median age of 35 years. RESULTS: Preoperative radiographs demonstrated degenerative changes in 13% of the knees. Articular cartilage pathology was found in 66% and a localized cartilage defect was found in 20% of the knees. A localized full-thickness cartilage lesion (ICRS grade 3 and 4) was observed in 11% of the knees. Of the localized full-thickness lesions, 55% (6% of all knees) had a size above 2 cm(2). CONCLUSION: Eleven percent of all knee arthroscopies show cartilage defects that may be suitable for cartilage repair procedures. However, the natural history of these lesions and the number of patients that will benefit from a cartilage repair procedure are so far unknown.

Adolescent↗

Irrigating solutions used in arthroscopy and their effect on articular cartilage. An in vivo study.

The effect of arthroscopic irrigating solutions on articular cartilage was determined by the use of an animal model. Rabbit knee joints were irrigated continuously for two hours with either normal saline, Ringer's lactate, or sterile water. Subsequently, the rate of incorporation of 35SO4 by articular cartilage was used to measure the effect of the irrigants on chondrocyte metabolism. In addition, the irrigated groups were compared to an unirrigated control group. There was no significant difference in 35SO4 incorporation between the groups. This suggested that none of the irrigating solutions used in this study adversely affected articular cartilage function. On the basis of these findings, it appears that normal saline, Ringer's lactate, and sterile water can be safely used as irrigating solutions during most arthroscopic procedures.

Animals↗

Involvement of ATP, increase of intracellular calcium and the early expression of c-fos in the repair of rat fetal articular cartilage.

To compare the potential of adult and fetal animals to repair articular cartilage, we investigated the early process after creating superficial defects in the femoral knee cartilage in rat models. In fetuses at 19 days of gestation, both chondrocytes and the extracellular matrix responded notably by 48 h after artificial injury. Staining patterns with safranin O revealed that, by 1 h after injury, some components of the extracellular matrix around the wound were modified, and the change spread from the limited region to the entire knee cartilage within 24 h. The chondrocytes in the area surrounding the wound transiently expressed increased level of c-fos from 1 h to 6 h. The wound remained 1 day after birth, i.e., 72 h after injury, but was completely repaired 10 days after birth. In contrast, neither visible responses nor transient c-fos expression was observed in 12-week-old adult articular cartilage 48 h after injury. We also examined the relationships between the intracellular Ca2+ concentration ([Ca2+]i) and the induction of c-fos expression in the cartilage. Applications of ATP or Ca2+ ionophore A23187, both of which increase [Ca2+]i, induced immediate expression of c-fos in primary cultured chondrocytes: 1 microM ATP elicited an increase of [Ca2+]i in chondrocytes in fetal cartilage slices, but 1 mM was required in adult cartilage slices. Our findings show the presence of a signaling pathway that is apparently active in the repair of fetal but not adult articular cartilage and that involves the intercellular transfer of ATP, increase of [Ca2+]i, and expression of c-fos in cartilage.

Adenosine Triphosphate↗

Ex vivo synthesis of articular cartilage.

This review discusses modern methods used for the synthesis of articular cartilage ex vivo. The value of culturing articular chondrocytes as a monolayer and in three-dimensional lattices is discussed. Of particular interest are techniques involving seeding of chondrocytes onto synthetic, biodegradable, polymeric scaffolds, and natural materials, such as collagen and agarose. Also discussed is the use of bioreactors to modulate the fluid-flow-induced shear environment of cell-seeded scaffolds. Biodegradable scaffolds are central to the efforts to tissue engineer articular cartilage ex vivo. A review of salient efforts to design and use such scaffolds is presented, along with our thoughts on potential future improvements.

Animals↗

A finite element analysis methodology for representing the articular cartilage functional structure.

Recognising that the unique biomechanical properties of articular cartilage are a consequence of its structure, this paper describes a finite element methodology which explicitly represents this structure using a modified overlay element model. The validity of this novel concept was then tested by using it to predict the axial curling forces generated by cartilage matrices subjected to saline solutions of known molality and concentration in a novel experimental protocol. Our results show that the finite element modelling methodology accurately represents the intrinsic biomechanical state of the cartilage matrix and can be used to predict its transient load-carriage behaviour. We conclude that this ability to represent the intrinsic swollen condition of a given cartilage matrix offers a viable avenue for numerical analysis of degenerate articular cartilage and also those matrices affected by disease.

Animals↗

Repair of articular cartilage defects with osteogenic protein-1 (BMP-7) in dogs.

BACKGROUND: Articular cartilage injury has a poor prognosis for repair. Mesenchymal cells, when exposed to osteogenic proteins and other cytokines, can differentiate into cells that behave phenotypically as chondrocytes. In this study, we examined the ability of recombinant human osteogenic protein-1 (rhOP-1 or rhBMP-7) to elicit the repair of osteochondral defects in dogs. METHODS: Bilateral osteochondral defects that were 5 mm in diameter by 6 mm deep were surgically created in the medial femoral condyles of sixty-five adult dogs. rhOP-1-treated (100 mg of a 3.5-mg rhOP-1/g bovine bone-derived Type-I collagen device) and control defects (untreated or treated with 100 mg bovine bone-derived collagen implants) were evaluated grossly and histologically at six, twelve, sixteen, twenty-six, and fifty-two weeks postoperatively. The influence of protected initial weight-bearing and surgical placement of periosteal flaps was also evaluated. RESULTS: Gross and histologic grading of the defect repair indicated improvement in the rhOP-1-treated defects compared with that in the controls. Grossly, the repair tissue in the rhOP-1-treated defects was continuous with the adjacent intact cartilage and appeared translucent. By comparison, the repair tissue in the control defects was discontinuous and opaque or inhomogeneous in nature. Histologically, maturing cartilage similar in appearance to the intact articular cartilage was present in the rhOP-1-treated defects. Cartilage at the defect interface was minimally degraded. The control defects were filled primarily with fibrous tissue and fibrocartilage. Significant differences based upon treatment type were observed at twelve weeks, sixteen weeks, and for all time-periods combined (p = 0.0385, p = 0.0070, and p = 0.0026, respectively). CONCLUSION: rhOP-1 (rhBMP-7) induced hyaline cartilage-like repair of full-thickness osteochondral defects in a dog model. Differences in cartilage repair were maintained at fifty-two weeks postoperatively with no significant degradation of the rhOP-1-induced repair tissue.

Animals↗

Localized regressive articular cartilage changes in the hip joint of the rabbit following an induced synovitis.

A talcum induced synovitis in the hip joint of the rabbit, which is known to cause articular cartilage hyperplasia followed by femoral head protrusion and joint incongruency, has in the present experiment also been shown to lead to localized regressive articular cartilage changes. The articular cartilage of the hip joints in 40 rabbits was examined histologically, at intervals, following induction of such a talcum synovitis. Regressive changes in the form of loss of surface chondrocytes and glycosaminoglycans sometimes accompanied by fibrillation, were found in the area of the femoral head articular cartilage which had become flattened following the head protrusion. Chondrocyte cloning facilitated subsequent cartilage repair. The biomechanical disturbance in the joint following the induced synovitis is felt to have caused the regressive changes. The experiment is considered to have some significance in connection with Legg-Calvé-Perthes' Syndrome (L.C.P.S.) in children.

Animals↗