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Influence of the mode of preparation on the long-term efficacy of homologous costal cartilage implants.

Devitalized homologous costal cartilage is widely employed as an implant in the management of the saddle nose. The tissue response induced by the implant is a combination of enveloping fibrosis and implant resorption, which will probably, ultimately, be complete. We have studied the balance between resorption and fibrosis, following different modes of cartilage preparation, in the mouse. Homologous costal cartilage was devitalized by four common methods--irradiation, formalin, glutaraldehyde and alcohol. Segments of this cartilage were inserted at separate sites in the subcutaneous plain of the tail. These implants were harvested after one year for histology. Variations in the mode of cartilage devitalization, while inducing variations in the degree of the tissue response, did not influence the balance between fibrosis and resorption. Thus the long term maintenance of tissue bulk following homologous cartilage implantation is not influenced by the mode of preparation. Evidence suggests that the ultimate cosmetic results of autologous and homologous costal cartilage implantation would be much the same, and the use of homologous cartilage must be justified on other grounds.

Animals↗

Age-related changes in the content of the C-terminal region of aggrecan in human articular cartilage.

The content of the C-terminal region of aggrecan was investigated in samples of articular cartilage from individuals ranging in age from newborn to 65 years. This region contains the globular G3 domain which is known to be removed from aggrecan in mature cartilage, probably by proteolytic cleavage, but the age-related changes in its abundance in human cartilage have not been described previously. The analysis was performed by immunosorbant assay using an antiserum (JD5) against recombinant amino acid residues of human aggrecan, on crude extracts of cartilage without further purification of aggrecan. The results showed that the content of the C-terminal region decreased with age relative to the G1 domain content (correlation coefficient = 0.463). This represented a 92% fall in the content of this region of the molecule from newborn to 65 years of age. furthermore, when the G1 content of the cartilage extracts was corrected to only include the G1 attached to aggrecan and to exclude the G1 fragments which accumulate as a by-product of normal aggrecan turnover (free G1), the age-related decrease in the C-terminal region remained very pronounced. Analysis by composite agarose/PAGE showed that the number of subpopulations of aggrecan resolved increased from one in newborn to three in adult cartilage. All of these reacted with an antiserum to the human G1 domain, but only the slowest migrating species reacted with the C-terminal region antiserum (JD5). Similar analysis by SDS/PAGE confirmed the presence of high-molecular-mass (200 kDa) proteins reactive with JD5, but no reactive fragments of lower electrophoretic mobility were detected. In contrast, when probed with the antiserum to the human G1 domain, the immunoblots showed protein species corresponding to the free G1 and G1-G2 fragments, which were present at high concentrations in adult cartilage. The results suggest that the loss of the C-terminal region is not directly part of the process of aggrecan turnover, but it is a slow independent matrix process that occurs more extensively with aging as turnover rates become slower. Young cartilage with the fastest turnover contains least molecules lacking the C-terminal region, whereas in old tissue with slow turnover few molecules retain this region. An increase in the cleavage of this region with age may also contribute to this change. The content of the C-terminal region may thus give a measure of the abundance of newly synthesized aggrecan.

Adolescent↗

Requirement of fibroblast growth factor signaling for regeneration of epiphyseal morphology in rabbit full-thickness defects of articular cartilage.

The involvement of fibroblast growth factor-2 (FGF-2) during the repair process in rabbit full-thickness defects of articular cartilage was studied. Fibroblast growth factor-2 (50 pg/h) was administered for 2 weeks in a 5 mm defect of articular cartilage, which is large enough not to repair spontaneously. The administration of FGF-2 resulted in the regeneration of the articular cartilage and the subchondral bone within 8 weeks. In these defects, undifferentiated mesenchymal cells initiated chondrogenic differentiation coupled with replacement by subchondral bone, resulting in the resurfacing of the defects with hyaline cartilage and the recovery of subchondral bone up to the original bone-articular cartilage junction. In rabbits, full-thickness defects are capable of regenerating articular cartilage as long as the defect size is limited to < or = 3 mm in diameter. In the defects, strong immunoreactivity for FGF-2 was observed in the granulation tissue filling the defects in the early stage of repair, in association with the expression of FGF-2 mRNA shown by in situ hybridization. Once the undifferentiated mesenchymal cells had differentiated into chondrocytes, both the immunoreactivity and the in situ hybridization signal declined significantly. Upon the local administration of a monoclonal antibody against FGF-2 (bFM-1, 50 ng/h), the defects were filled with fibrous tissue and no resurfacing hyaline cartilage was formed. Compared to the non-treated defects, there were marked increases in FGF-2 immunoreactivity and the overexpression of FGF-2 mRNA in the reparative tissue in the bFM-1-treated defects. This rebound phenomenon indicates that the autocrine FGF-2 signaling is critically important for the regeneration of articular cartilage.

3T3 Cells↗

Distribution of cartilage thickness on the head of the human first metatarsal bone.

Articular hyaline cartilage takes on the contours of the subchondral bone on which it lies, but its thickness varies between joints, within a single joint and within a single articular surface. Previous studies have correlated articular cartilage thickness distribution with the degree of stress and weight bearing on joint surfaces, but few studies have considered the thickness of the calcified cartilage in relation to these parameters. Here we report a correlation between the cartilage thickness distribution and weight bearing distribution on the head of the 1st metatarsal bone, a component of one of the major weight bearing joints in the lower extremity during the gait cycle. The greatest total and uncalcified articular cartilage thickness was found on the central and lateral distal aspects of the metatarsal head, a region that receives maximal ground reactive force during the propulsive phase of the normal gait cycle. Although the thickness of the calcified cartilage was correlated with the thickness of the uncalcified cartilage, it varied to a lesser extent across the articular surface than did that of the uncalcified cartilage.

Adult↗

Healing of defects in canine articular cartilage: distribution of nonvascular alpha-smooth muscle actin-containing cells.

The objective of this study was to evaluate the types of tissue resulting from spontaneous healing of surgically created defects in adult canine articular cartilage up to 29 weeks postoperatively, with specific attention directed toward the presence and distribution of cells containing the contractile actin isoform, alpha-smooth muscle actin. Two 4-mm diameter defects were made in the trochlear groove to the depth of the tidemark in 20 adult mongrel dogs. The areal percentage of specific tissue types in the reparative material was determined histomorphometrically. Immunohistochemistry was employed to evaluate the percentage of alpha-smooth muscle actin-containing cells. The results showed that approximately 50% of the chondrocytes in the superficial zone of the uninvolved articular cartilage expressed alpha-smooth muscle actin. A significantly lower percentage of alpha-smooth muscle actin-positive chondrocytes appeared in the uninvolved deep zone. Notably, the deep zone adjacent to the defect contained a greater percentage of such cells than in the uninvolved deep zone. Also of interest was that a greater percentage of nonvascular cells in the hyaline cartilage and fibrocartilage of the reparative tissue contained alpha-smooth muscle actin-positive cells, compared to the fibrous tissue in the defects. The findings of this study revealed that canine articular cartilage has some potential for spontaneous regeneration, including integration with the calcified cartilage zone. By 29 weeks, up to 40% of an areal cross section of an untreated full-thickness chondral defect was found to fill with hyaline cartilage, with up to 19% judged histologically similar to articular cartilage. The results warrant further consideration of the role of alpha-smooth muscle actin in chondrocytes in normal articular cartilage and in reparative tissue.

Actins↗

Thermometric determination of cartilage matrix temperatures during thermal chondroplasty: comparison of bipolar and monopolar radiofrequency devices.

PURPOSE: To compare cartilage matrix temperatures between monopolar radiofrequency energy (mRFE) and bipolar RFE (bRFE) at 3 depths under the articular surface during thermal chondroplasty. We hypothesized that cartilage temperatures would be higher at all cartilage depths for the bRFE device than for the mRFE device. TYPE OF STUDY: Randomized trial using bovine cartilage. METHODS: Sixty osteochondral sections from the femoropatellar joint of 15 adult cattle were used for this study. Using a custom jig, fluoroptic thermometry probes were placed at one of the following depths under the articular surface: 200 microm, 500 microm, or 2,000 microm. RF treatment was performed either with fluid flow (F) (120 mL/min) or without fluid flow (NF) (n = 5/depth/RFE device/flow; total specimens, 60). Irrigation fluid temperature was room temperature (22 degrees C). Thermometry data were acquired at 4 Hz for 5 seconds with the RF probe off, for 20 seconds with the RF probe on, and then for 15 seconds with the RF probe off. During RF treatment, a 0.79-cm2 area (1.0-cm diameter) of the articular surface centered over the thermometry probe was treated in a paintbrush manner in noncontact (bRFE) or light contact (mRFE). RESULTS: Thermal chondroplasty with bRFE resulted in higher cartilage matrix temperatures compared with mRFE for all depths and regardless of fluid flow. Bipolar RFE resulted in temperatures of 95 degrees C to 100 degrees C at 200 microm and 500 microm under the surface, with temperatures of 75 degrees C to 78 degrees C at 2,000 microm. Fluid flow during bRFE application had no effect at 200 microm. Monopolar RFE resulted in temperatures of 61 degrees C to 68 degrees C at 200 microm, 54 degrees C to 70 degrees C at 500 microm under the surface, and 28 degrees C to 30 degrees C at 2,000 microm below the surface. A significant effect of fluid flow during mRFE application occurred at 200 microm (NF, 61 degrees C; F, 63 degrees C) and 500 microm (NF, 53 degrees C; F, 68 degrees C). CONCLUSIONS: In this study, we found significant differences between bRFE and a temperature-controlled mRFE device with regard to depth of thermal heating of cartilage in vitro. Bipolar RFE resulted in matrix temperatures high enough (>70 degrees C) to kill cells as deep as 2,000 microm under the articular surface. Fluid flow during thermal chondroplasty had the effect of significantly increasing cartilage matrix temperatures at 200 and 500 microm with the mRFE device. During thermal chondroplasty, bRFE creates greater matrix temperature elevations at equivalent depths and treatment duration than does mRFE. Excessive temperatures generated deep within the cartilage matrix could cause full-thickness chondrocyte death, in vivo.

Animals↗

Arthroscopic evaluation of articular cartilage lesions in posterior-cruciate-ligament-deficient knees.

PURPOSE: The goal of this study was to gain more information on the likelihood of developing cartilage lesions in posterior cruciate ligament (PCL)-deficient knees. TYPE OF STUDY: Retrospective clinical study. METHODS: Standardized arthroscopy records of 181 patients with a nonsurgically treated acute or chronic PCL injury were analyzed with respect to cartilage degeneration. Subgroups with different duration of PCL insufficiency, the influence of isolated PCL or combined PCL/posterolateral instability, and the grade of posterior laxity was analyzed. RESULTS: PCL insufficiency significantly increased the risk of developing medial femoral condyle and patellar cartilage degeneration over time. Of patients whose PCL deficiency was present for more than 5 years, 77.8% showed degenerative cartilage lesions of the medial femoral condyle and 46.7% showed cartilage degeneration of the patella. After 1 year of PCL insufficiency, the number of medial femoral cartilage lesions increased threefold (13.6% v 39.1%). With the presence of combined PCL/posterolateral insufficiency the amount of medial femoral degeneration was significantly increased (36.6% v 60.6%). CONCLUSIONS: We found that PCL insufficiency is not a benign injury with respect to the development of degenerative articular cartilage lesions. The early and continuous increase in cartilage degeneration at the medial femoral condyle and the patella should be considered when discussing operative versus conservative treatment for a PCL-deficient knee. The rapid development of medial arthritis should also be considered during decision making, particularly in patients with combined PCL/posterolateral instability or those who underwent previous partial medial menisectomy.

Adolescent↗

The effects of intra-articular methylprednisolone and exercise on the mechanical properties of articular cartilage in the horse.

INTRODUCTION: Intra-articular corticosteroids are widely used as anti-inflammatory agents for symptomatic management of arthritis, but their administration with concurrent exercise remains controversial. Biochemical and morphologic analysis of treated cartilage has revealed conflicting results, but previous biomechanical assessment has not been undertaken. OBJECTIVE: To compare the biomechanical properties of intra-articular methylprednisolone acetate (MPA) and diluent treated cartilage in treadmill exercised horses. METHODS: Eight 2-year-old female horses had MPA or diluent administered into contralateral middle carpal joints at 14 day intervals for a total of four treatments per horse. Horses underwent a standard treadmill exercise protocol until euthanasia (day 70). Standard sites were tested on the third, radial and intermediate carpal bones using an automated indentation apparatus to obtain the creep and recovery behavior of the articular cartilage. Using previously validated biphasic creep indentation methodology, aggregate modulus, Poisson's ratio, permeability, shear modulus, thickness, creep and recovery equilibrium times and percent recovery were obtained at each site. Results were analyzed using ANOVA and multiple comparisons of the means (P < 0.05). RESULTS: Cartilage intrinsic material properties and thickness demonstrated significant differences between MPA and diluent treated joints. Diluent treated cartilage had a 97% increase in compressive stiffness modulus (P = 0.0001), was 121% more permeable (P = 0.0001), had 88% increase in shear modulus (P = 0.0001), and was 24% thicker (P = 0.0001) than MPA treated articular cartilage. CONCLUSIONS: The findings indicate that repetitive intra-articular administration of MPA to exercising horses alters the mechanical integrity of articular cartilage, which could lead to early cartilage degeneration.

Analysis of Variance↗

Resurfacing of articular cartilage explants with genetically-modified human chondrocytes in vitro.

OBJECTIVE: We are attempting to genetically-modify chondrocytes transplanted to cartilage in vitro as a prelude to gene therapy trials in patients with osteoarthritis. DESIGN: With human cartilage and chondrocytes, we have explored the duration of binding of chondrocytes to cartilage in vitro and the expression of the beta-galactosidase gene introduced into the chondrocytes through infection with an adenoviral vector both before and after transplant of the chondrocytes to cartilage. RESULTS: Transplanted chondrocytes continued to bind to cartilage explants at 45 days in our longest trial. We could successfully infect chondrocytes with adenovirus at least 35 days after we transplanted the chondrocytes to cartilage. Expression of the beta-galactosidase gene continued throughout the duration of each trial. CONCLUSIONS: These results raise the possibility of repairing and rebuilding cartilage by resurfacing the cartilage with genetically modified chondrocytes. The ability to infect chondrocytes well after transplant raises the possibility of repeated infections of surface chondrocytes as an alternative to repeated injections of chondrocytes into the joint space.

Adenoviridae↗

Osteoarthritic cartilage loses its ability to remain avascular.

OBJECTIVE: To determine whether human osteoarthritic (OA) cartilage loses its ability to remain avascular when placed into the in-vivo model of angiogenesis, the chick embryo chorio-allantoic membrane (CAM), and to determine specific changes that occur in the cartilage matrix when the cartilage is exposed to an active vasculature. DESIGN: Articular cartilage from OA and non-OA joints was grafted onto the CAM for up to 5 days before fixing and processing for histological, histochemical and immunological examination for specific changes in proteoglycan and collagen. RESULTS: OA cartilage, but not non-OA cartilage, showed invasion of its matrix by blood vessels from the CAM to various extents. Associated with these blood vessels was a loss of staining for proteoglycans and cartilage specific glycosaminoglycans (GAG). A deposition of collagen types I and X was also visualized around the invasive vessels. CONCLUSIONS: OA cartilage loses or has already lost its ability to remain avascular when placed onto the chick CAM. Changes occur in the matrix around the invasive blood vessels, specifically a loss of proteoglycan and GAG, and the deposition of new collagen types, notably I and X.

Aged↗

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↗

Assessment of rat articular cartilage maturation using 50-MHz quantitative ultrasonography.

OBJECTIVE: The objective was to assess the relationship between maturation-related structural changes of articular cartilage and variations of acoustic parameters estimated using high frequency ultrasonography. DESIGN: Patellae taken from 48 immature Wistar male rats and divided into six age groups (from five to 11 weeks old) were explored in vitro using 50-MHz scanning acoustic microscopy, then assessed by histology for the analysis of the cartilage cell distribution and fibrillar collagen organization. The variation of cartilage proteoglycan and collagen content with age was evaluated. Thickness measurements performed on both B-scan images and histologic sections were compared. Ultrasonic radiofrequency signals reflected by the cartilage surface and backscattered from its internal matrix were processed to estimate the integrated reflection coefficient (IRC) and apparent integrated backscatter (AIB). RESULTS: One-way ANOVA indicated that acoustic parameters and thickness change significantly (P < 0.05) as the animal matures because of age-related changes in cartilage composition and morphology. A moderate correlation was found between IRC and the animal age. The parameter decreased slightly but significantly over time. However, a good correlation was observed between the rat age and the AIB, which decreased significantly over time. The parameter variation was mostly related to the changes in collagen fiber orientation, and/or to a change in cell size, density and organization. CONCLUSIONS: Current results indicate that acoustic properties of cartilage are affected by maturation-related cartilage changes. This suggests that high frequency ultrasonography may serve as a useful means for the investigation of cartilage matrix structural changes occurring under various clinical circumstances, like those observed during osteoarthritis, and for the evaluation of the efficacy of specific therapeutics.

Aging↗

High-resolution MRI detects cartilage swelling at the early stages of experimental osteoarthritis.

OBJECTIVE: The progressive early changes in cartilage and subchondral bone in an experimental model of osteoarthritis (OA) were investigated with high-resolution magnetic resonance imaging (MRI) and microradiography. METHODS: Partial medial meniscectomy was performed in the left knee of 16 rabbits. Four normal and four sham-operated additional rabbits were used as controls. Changes in cartilage and subchondral bone were sequentially assessed after surgery with MRI at 0, 2, 4, 6, 8 and 10 weeks, subchondral bone variations quantified postoperatively on microradiographs of sagittal sections at 6 and 10 weeks and the macroscopic alterations graded according to the severity of joint changes. RESULTS: MRI demonstrated a progressive increase in the articular cartilage thickness in the weight-bearing area of the femur at weeks 4, 6 and 8 vs basal. Tibial cartilage thickness only showed a significant increment at week 6. No significant abnormalities were detected on X-rays in subchondral bone when compared to controls. Macroscopically, 4 weeks after the operation OA rabbits had only slight cartilage discoloration. Cartilage eburnation, pitting, superficial erosions and osteophytes were detected at week 6. These abnormalities were more evident at 8 and 10 weeks after meniscectomy. CONCLUSION: The focal increase in cartilage thickness is one of the earliest measurable changes in OA and preceeds subchondral bone remodeling. The measurement of cartilage thickness variations with MRI can be used to follow the course of OA and to evaluate the potential beneficial effect of novel therapies.

Animals↗

Regulation of the nitric oxide production resulting from the glucocorticoid-insensitive expression of iNOS in human osteoarthritic cartilage.

OBJECTIVE: Nitric oxide (NO) produced by cartilage and synovial membranes is implicated in the pathogenesis of osteoarthritis (OA) and inhibitors of NO synthesis may have indications in the treatment or prevention of joint destruction in OA. Because the signaling mechanisms as well as the NOS isoform involved in induction of NO production in human cartilage remain in many parts unclear, the present study was designed to investigate the regulation of inducible NO synthesis in human intact OA cartilage. METHODS: Cartilage specimens were collected from OA patients undergoing knee replacement surgery and studied for iNOS expression and NO production in organ culture to allow intact chondrocyte-matrix interactions. J774 macrophages were used for comparison as a well-documented source of iNOS. RESULTS: OA cartilage expressed iNOS and produced NO in the absence of exogenous cytokines. Addition of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha) or lipopolysaccharide (LPS) into the culture medium enhanced NO production in a dose-and time-dependent manner. Various NOS inhibitors suppressed NO production in the following order of potency: 1400W (novel selective iNOS inhibitor)=L-NIO>L-NMMA>L-NAME. Cycloheximide (an inhibitor of protein synthesis), pyrrolidine dithiocarbamate (PDTC; an NF-kappa B inhibitor) and genistein (an inhibitor of tyrosine protein kinases) inhibited cytokine-induced NO production, while dexamethasone, diaminohydroxypyrimidine (DAHP; an inhibitor of tetrahydrobiopterin synthesis) and PD 98059 (p42/44 MAP kinase inhibitor) had no effect. CONCLUSIONS: The results suggest that NO synthesis in human osteoarthritic cartilage derives from the glucocorticoid-insensitive expression of iNOS. Very similar mechanisms appear to regulate inducible NO synthesis in human osteoarthritic cartilage and J774 macrophages with the exception that dexamethasone inhibited NO production in J774 cells but not in osteoarthritic cartilage.

Analysis of Variance↗

Comparison of collagenase-cleaved articular cartilage collagen in mice in the naturally occurring STR/ort model of osteoarthritis and in collagen-induced arthritis.

OBJECTIVE: The STR/ort mouse develops a naturally occurring osteoarthritis of the femorotibial joint that provides a model with which to establish the time course of biochemical changes taking place in articular cartilage in the disease. Our objective was to define the onset, location and progression of type II collagen cleavage by collagenase in the tibial cartilage of the STR/ort mouse. For comparison, cartilage collagen cleavage was also studied in collagen-induced arthritis in DBA mice. DESIGN: STR and control CBA mice aged 6-45 weeks were examined. DBA/1 mice were studied 2 and 3 weeks after initiating collagen-induced arthritis. Collagen cleavage was detected by immunolocalization using the antibody COL2-3/4Cshort which recognizes a carboxy terminal neoepitope created by collagenase cleavage of type I and II collagens. RESULTS: No COL 2-3/4Cshort immunostaining was observed in the intact cartilage of healthy young or old mice. The earliest detectable collagen degradation occurred at the cartilage surface coincident with the appearance of surface roughening. As fibrillations developed, further collagen degradation was evident around the edge of the lesion and in adjacent extracellular matrix. In contrast, staining was observed throughout the cartilage matrix in type II collagen-induced arthritis prior to the development of histopathological lesions. CONCLUSION: No evidence was found for collagen cleavage in intact/pre-lesional cartilage from STR/ort mice. Local collagen cleavage was, however, clearly associated with very early histopathological lesions and immunostaining with COL 2-3/4Cshort increased with progression of the latter. In contrast, type II collagen cleavage occurs throughout the articular cartilage at an early stage in collagen-induced arthritis.

Animals↗

Detection of changes in cartilage water content using MRI T2-mapping in vivo.

OBJECTIVES: Osteoarthritis (OA) is the most prevalent chronic disease in the elderly, and it is generally diagnosed at an advanced state when treatment is difficult if not impossible. The early form of OA is characterized by an elevated water content in the cartilage tissue. The purpose of this study was to verify in vivo if changes in the water content of patellar cartilage typically occurring in early OA can be detected using T(2) mapping MRI methods. DESIGN: Twenty healthy volunteers performed 60 knee bends in order to compress their patellar cartilage thereby reducing its water content. MR images of the patellar cartilage were acquired immediately following exercise and after 45 min of rest. Patellar cartilage thickness and T(2) maps were determined and their difference between the time points evaluated. RESULTS: Cartilage thickness increased by 5.4+/-1.5% from 2.94+/-0.15 mm to 3.10+/-0.15 mm (P< 0.001) following 45 min of rest, while T(2) increased by 2.6+/-1.0% from 23.1+/-0.5 ms to 23.7+/-0.6 ms (P< 0.05). CONCLUSION: Small, physiologic changes in the water content of patellar cartilage and the concomitant change in proteoglycan and collagen density following exercise can be detected using MRI. The proposed T(2)-mapping method, together with other non-invasive MR cartilage imaging techniques, could aid in the early diagnosis of OA.

Adult↗

No loss of cartilage volume over three years in patients with knee osteoarthritis as assessed by magnetic resonance imaging.

OBJECTIVE: Magnetic resonance imaging (MRI) has the potential to provide accurate quantification of structural changes in joint disease, with sensitivity to change, as it can provide direct visualization of the cartilage and bone. In this study, we investigated whether knee cartilage volume, as assessed by MRI, is sensitive to change over time in patients with osteoarthritis (OA). DESIGN: Sixteen patient volunteers (10 male, six female) with established OA of the knee were entered into the study and demographic data recorded. At baseline, 12 months and 37+/-2 months, patients underwent simple measures of disease severity, as well as extended weight-bearing AP knee X-rays. In addition the patient's index knee was imaged using MR at 1.0 T using a 3-D spoiled gradient-echo sequence with fat-suppression, repetition time 50 ms, echo time 11 ms, flip-angle 40 degrees, sagittal slice thickness 1.56 mm and in-plane pixel resolution 0.55 mm. Manual image segmentation was performed on all knee cartilage compartments and the respective cartilage volumes determined. RESULTS: Eleven of the original patients recruited completed the 3-year study. Radiographic features indicated that the majority had a spectrum of well-established OA at entry. The average decrease in medial tibiofemoral joint space width was 0.21+/-0.37 mm (mean+/-S.D.). Comparison of MR images at baseline and 37+/-2 months indicated little evidence of cartilage lesion shape or size change in any of the compartments. There was no significant MRI volume change in any of the knee cartilage compartments over the course of 1 year. The change in total knee cartilage volume, as measured by MRI, was a loss of only 1.6%, or 0.36+/-1.3 ml (mean+/-S.D.), over the 3 years. CONCLUSIONS: The failure to identify loss of cartilage volume over 3 years in this cohort of patients with established knee OA using MRI challenges the face validity of this endpoint to assess structural changes in OA.

Aged↗

Analysis of rabbit articular cartilage repair after chondrocyte implantation using optical coherence tomography.

OBJECTIVE: To evaluate the utility and limitations of optical coherence tomography (OCT) for immediate, high-resolution structural analysis of rabbit articular repair tissue following chondrocyte implantation without excising or sectioning the specimen. METHODS: Full thickness articular cartilage defects were created in the patellar grooves of 30 adult rabbit knee joints. Allogenic cultured chondrocytes embedded in collagen gels were implanted into the surgical defects. A periosteal patch was then sutured over the chondrocyte-collagen composites. Six animals per time point were sacrificed at 2, 4, 8, 12 and 24 weeks after surgery. The repair tissues were sequentially analysed by arthroscopic surface imaging, OCT, and histology. The resulting images were compared to determine qualitative and quantitative features of surface roughness, repair tissue integration, and micro-architecture. Statistical analysis was performed using Student's t -testing and linear regression. RESULTS: OCT was able to identify the bone and cartilage interface in normal rabbit articular cartilage and regenerated cartilage at 24 weeks post chondrocyte implantation. OCT was able to identify hypertrophy at 4 and 8 weeks, and subtle surface fibrillations at 24 weeks, comparable with histological analysis at low magnification (20x). More importantly, OCT was able to detect embedded gaps between the repair tissue and surrounding host cartilage. CONCLUSION: Close correlation was observed between OCT and histological analysis of morphological features important to the assessment of articular cartilage repair. These results demonstrate that OCT is capable of providing immediate 'optical biopsy' of the rabbit articular cartilage repair tissue without damaging the specimen, and suggest that this new technique, if integrated with an arthroscope, can potentially be used in longitudinal studies of articular cartilage repair in vivo.

Animals↗