Abnormal expression of Col X, PTHrP, TGF-β, bFGF, and VEGF in cartilage with Kashin–Beck disease

The purpose of the current study was to investigate the abnormal expression of Col X, PTHrP, TGF-β, bFGF, and VEGF in cartilage from patients with Kashin–Beck disease (KBD) to understand the pathogenesis of chondronecrosis in KBD. Articular cartilage and growth plate cartilage collected were divided into four groups: control children (8 samples, 5 cases), KBD children (19 samples, 9 cases), control adults (8 samples, 6 cases), and KBD adults (16 samples, 15 cases). The presence of PTHrP, TGF-β₁, bFGF, VEGF, and collagen X in articular cartilage and in growth plate cartilage was analyzed by immunohistochemistry. Articular cartilage and growth plate were each divided in three zones, and the rate of positive cells was counted by light microscope for cytoplasmic and pericellular staining. Results showed that (1) in KBD children, Col X expression was lower in the deep zone of growth plate cartilage than in normal children; in articular cartilage of KBD adults, however, collagen X expression was higher in the middle zone compared to the controls; (2) staining for bFGF, PTHrP, TGF-β₁, and VEGF in KBD adult patients was prominent in the chondrocyte clusters and the eroded surface of articular cartilage, and the percentage of chondrocyte staining was significantly higher than in control samples (t = 3.64–10.34, df = 12 for children and 19 for adults, P = 0.002–0.0001); and (3) the enhanced PTHrP, TGF-β₁, and VEGF staining in the deep and middle zone of KBD articular cartilage correlated with the high incidence of chondronecrosis in the middle zone (48.5% ± 10.2%) and deep zone (70.6% ± 27.0%) of adult KBD cartilage. In conclusion, Col X expression was reduced in areas of chondrocyte necrosis in the deep zone of KBD articular cartilage, indicating changes in terminal chondrocyte differentiation. PTHrP, TGF-β₁, and VEGF expression was significantly altered and indicated degenerative changes in KBD cartilage, which initially resemble those occurring in osteoarthritis, but lead eventually to chondronecrosis, an event not observed in osteoarthritis.     

T1ρ/T2 mapping and histopathology of degenerative cartilage in advanced knee osteoarthritis

AIM To investigate whether normal thickness cartilage in osteoarthritic knees demonstrate depletion of proteoglycan or collagen content compared to healthy knees.METHODS Magnetic resonance(MR) images were acquired from5 subjects scheduled for total knee arthroplasty(TKA)(mean age 70 years) and 20 young healthy control subjects without knee pain(mean age 28.9 years). MR images of T1ρ mapping, T2 mapping, and fat suppressed proton-density weighted sequences were obtained.Following TKA each condyle was divided into 4 parts(distal medial, posterior medial, distal lateral, posterior lateral) for cartilage analysis. Twenty specimens(bone and cartilage blocks) were examined. For each joint,the degree and extent of cartilage destruction was determined using the Osteoarthritis Research Society International cartilage histopathology assessment system.In magnetic resonance imaging(MRI) analysis, 2 readers performed cartilage segmentation for T1ρ/T2 values and cartilage thickness measurement.RESULTS Eleven areas in MRI including normal or near normal cartilage thickness were selected. The corresponding histopathological sections demonstrated mild to moderate osteoarthritis(OA). There was no significant difference in cartilage thickness in MRI between control and advanced OA samples [medial distal condyle, P = 0.461;medial posterior condyle(MPC), P = 0.352; lateral distal condyle, P = 0.654; lateral posterior condyle, P = 0.550],suggesting arthritic specimens were morphologically similar to normal or early staged degenerative cartilage.Cartilage T2 and T1ρ values from the MPC were significantly higher among the patients with advanced OA(P= 0.043). For remaining condylar samples there was no statistical difference in T2 and T1ρ values between cases and controls but there was a trend towards higher values in advanced OA patients. CONCLUSION Though cartilage is morphologically normal or near normal, degenerative changes exist in advanced OA patients. These changes can be detected with T2 and T1ρ MRI techniques.