title: Regional differences of tibial and femoral cartilage in the chondrocyte gene expression, immunhistochemistry and composite in different stages of osteoarthritis.
abstract: The function of articular cartilage as an avascular tissue is mainly served by collagen type II and proteoglycan molecules. Within this matrix homeostasis between production and breakdown of the matrix is exceptionally sensitive. The current study was conducted to identify regional differences in specific alterations in cartilage composition during the osteoarthritic process of the human knee joint. Therefor the changes in the expression of the key molecules of the extracellular matrix were measured in dependence of the anatomical side (femoral vs tibial) and associated with immunohistochemistry and quantitative measurement. 60 serial osteochondral femoral condyle and the tibial plateau samples of patients undergoing implantation of total knee endoprosthesis of areas showing mild (Group A, macroscopically ICRS grade 1b) respectively advanced (Group B, macroscopically ICRS grade 3a/3b) (30 each) osteoarthritis according to the histological-histochemical grading system (HHGS) were compared with 20 healthy biopsies with immunohistochemistry and histology. We quantified our results on the gene expression of collagen type I and II and aggrecan with the help of real-time (RT)-PCR. Proteoglycan content was measured colorometrically. In group A slightly increased colour intensity was found for collagen II in deeper layers, suggesting a persisting but initially still intact repair process. But especially on the medial tibia plateau the initial Col II increase in gene expression is followed by a decrease leading to the lowest over all Col II expression on the medial plateau, here especially in the central part. There in late stage diseases the collagen type I expression was also more pronounced. Markedly decreased safranin O staining intensity was observed in the radial zone and less reduced intensity in the transitional zone with loss of zonal anatomy in 40% of the specimens in group A and all specimens in group B. Correlation between colorometrically analysed proteoglycan GAG content and aggrecan Real Time PCR is mainly weak. Tibial and femoral cartilage in contrast to patellar cartilage both are preferential exposed to compressive stresses, but presence of menisci affects the load distribution at the tibial side, which creates varying conditions for the different cartilage surfaces in the knee. As directly measured Poissońs ratio in tibial cartilage is higher but Younǵs modulus is lower than in femoral cartilage, different resulting feedback amplification loops interact with proceeding cartilage damage. The initial loss of aggrecan may support Matrix metalloproteinases (Mmps) in the access to the collagen network and the considerably differing mechanical properties at both joint surfaces result in varying increased synthesis and release of matrix degrading enzymes. The present study has identified a selection of events which reflect the response of cartilage structure and composite, chondrocytes itself and their productivity to changes in mechanical stress depending on the anatomical site.
authors.affiliation: Department of Orthopaedics and Orthopaedic Surgery, Ernst-Moritz-Arndt University Greifswald, F.-Sauerbruch Str., D-17475 Greifswald, Germany; Kliniken Maria Hilf Mönchengladbach, Academic Teaching Hospital of the RWTH Aachen, Viersener Str. 450, D-41061 Mönchengladbach, Germany. Electronic address: alahm@uni-greifswald.de.
authors.forename: A
authors.initials: A
authors.lastname: Lahm
authors.affiliation: Department of Orthopaedics and Orthopaedic Surgery, Ernst-Moritz-Arndt University Greifswald, F.-Sauerbruch Str., D-17475 Greifswald, Germany; Center for Orthopaedics and Spinal Surgery, Klinikum Fichtelgebirge, Weißenbacher Str. 62, D-95100 Selb, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Dabravolski
authors.affiliation: Department of Orthopaedics and Orthopaedic Surgery, Ernst-Moritz-Arndt University Greifswald, F.-Sauerbruch Str., D-17475 Greifswald, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Spank
authors.affiliation: Department of Orthopaedics and Orthopaedic Surgery, Ernst-Moritz-Arndt University Greifswald, F.-Sauerbruch Str., D-17475 Greifswald, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Merk
authors.affiliation: Department of Orthopaedics and Orthopaedic Surgery, Ernst-Moritz-Arndt University Greifswald, F.-Sauerbruch Str., D-17475 Greifswald, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Esser
authors.affiliation: Department of Orthopaedics and Orthopaedic Surgery, Ernst-Moritz-Arndt University Greifswald, F.-Sauerbruch Str., D-17475 Greifswald, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kasch
mesh_terms: D000368:Aged; D053674:Aggrecans / Q000096:biosynthesis* / Q000235:genetics; D002358:Cartilage, Articular / Q000254:growth & development / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism; D024042:Collagen Type I / Q000096:biosynthesis* / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D024043:Collagen Type II / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005269:Femur / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007719:Knee Joint / Q000254:growth & development / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans / Q000096:biosynthesis; D013314:Stress, Mechanical; D013977:Tibia / Q000254:growth & development / Q000378:metabolism / Q000473:pathology
chemical_list: D053674:Aggrecans; C499177:COL2A1 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024043:Collagen Type II; D011509:Proteoglycans
keywords: Cartilage degeneration; Composite of tibial and femoral cartilage; PCR