Cartilage Collagen Neoepitope C2C Expression in the Articular Cartilage and Its Relation to Joint Tissue Damage in Patients with Knee Osteoarthritis.

Pathological cleavage of type II collagen (Col2) and generation of Col2 neoepitopes can serve as useful molecular markers of the progression of osteoarthritis (OA). One of such potential biomarkers is type II collagen neoepitope C2C. The aim of this study was to correlate the degree of articular cartilage damage in OA patients with C2C expression in histological samples of tissues removed during total knee replacement. Cartilage samples were obtained from 27 patients ranging in age from 55 to 66 years. In each patient, medial and lateral tibia plateau samples were analyzed according to the OARSI histopathology grading system. The C2C expression was evaluated on histological slides by semi-quantitative analysis using ImageJ Fiji 2.14.0 software. Spearman's rank correlation analysis revealed a positive weak correlation (rho = 0.289, p = 0.0356) between the histological grade of tissue damage and the percentage of C2C staining. In addition, a highly significant positive correlation (rho = 0.388, p = 0.0041) was discovered between the osteoarthritis score (combining the histological grade of damage with the OA macroscopic stage) and the percentage of C2C staining in the samples. The C2C expression was detected in all the regions of the articular cartilage (i.e., the superficial zone, mid zone, deep zone and tidemark area, and the zone of calcified cartilage). Our findings imply that local expression of C2C correlates with the articular cartilage damage in OA-affected knees. This confirms that C2C can be used as a prospective marker for assessing pathological changes in the OA course and OA clinical trials.

Morphological study of incompetent saphenous veins: apoptosis and ultrastructural changes of smooth muscle cells.

BACKGROUND: Varicose veins affect approximately 25% of people in industrialized countries. METHODS: The study aimed at detecting apoptotic cells and histopathological changes in varicose vein walls. Patients (N.=41) with varicose veins and 30 control group patients were divided into two groups according to their age (younger and older than 50 years). Apoptosis was determined by the TUNEL assay, elastin and collagen IV expression by immunohistochemistry and ultrastructural changes by transmission electron microscopy. RESULTS: The results show that the number of apoptotic cells in the layers of varicose veins increased, in particular in a group of patients aged over 50 years. In the varicose veins as compared to control veins the elastic fibers were found to be thinner, more fragmented and disorderly arranged. Elastin and collagen IV expression was found to decline in the intima and the media of varicose veins in both age groups. Electron microscopy demonstrated hypertrophy and degeneration of smooth muscle cells. Furthermore, cells with ultrastructural feature of apoptosis were noted. In the disorganized and expanded extracellular matrix membrane-bound vesicles, ghost bodies with different size and electron density were observed. Ghost bodies seem to bud off from smooth muscle cells and are likely to be involved in extracellular matrix remodeling as they are seen in close contact with collagen fibers. CONCLUSIONS: The study demonstrates increase of apoptotic cells in the wall of varicose veins along with vein wall structural abnormalities including alterations of smooth muscle cells and decline of elastin and collagen IV expression.

Expression of CILP-2 and DDR2 and ultrastructural changes in the articular cartilage of patients with knee osteoarthritis undergoing total knee arthroplasty: a pilot morphological study.

The aim of the study was to correlate the immunohistochemical expression of cartilage intermediate layer protein 2 (CILP-2) and discoidin domain receptor 2 (DDR2), and the ultrastructural changes in the cartilage with the degree of articular cartilage damage in osteoarthritis (OA) patients. Cartilage samples were obtained from twenty patients aged from 46 to 68 years undergoing total knee arthroplasty. In each patient, medial and lateral tibial plateau samples were analysed applying OARSI histopathology grading. Positive correlation was noted between the extent of CILP-2 staining intensity and OARSI grades. Abundant staining for CILP-2 was found in the superficial and middle layers and in the pericellular matrix (PCM) of the deep zone. Transmission electron microscopy studies demonstrated strong damage of chondrocytes, the organelles were often diminished or focally aggregated. As a characteristic finding, PCM was frequently expanded, which may reflect a pathogenic step in OA progression. In conclusion, CILP-2 may potentially be a relevant marker of OA progression as its expression correlated better with cartilage damage than the known marker of articular cartilage damage, DDR2.