Abstract
Purpose: Study of 846 as anabolic marker and C2C as catabolic marker of post-traumatic osteoarthritis (OA) in the rabbit model of anterior cruciate ligament transection (ACLT). Methods: Transection of the anterior cruciate ligament was performed in adult male New Zealand white rabbits (n = 32). An open arthrotomy surgery of only the right knees was used. Left knees remained untreated and served as intraindividual control knees. At time 0 before surgery and at 2, 4, 8 and 12 weeks before sacrifice, synovial fluid was aspirated from both, right and left knee joints. Use of all animals had been permitted by both, the University’s ethics committee and the government ethics committee (Regierungsprasidium Darmstadt, Germany). Macroscopic grading was performed of all right and left knee joints. 9 areas per each medial and lateral tibia, respectively medial and lateral femur and the patella were evaluated. Histologic grading was performed with a grading system accounting for proteoglycan content, matrix structure, cellularity, and osteophyte formation. 846 levels and C2C levels were measured in the synovial fluid lavages with immunoassays. The distributions of synovial fluid levels of 846 and C2C were statistically analysed (Kolmogorov-Smirnov-test). Differences between left and right knees were then statistically analysed by student’s t-test. Results: All rabbits had a normal postoperative course after ACLT. At 2 weeks after ACLT, macroscopically visible lesions were only detected at the medial femoral site (p< 0.05). With time, lesion size increased and lesions appeared at more joint sites. At 12 weeks after ACLT, medial and lateral tibiae as well as both femoral condyles showed statistically significant lesions. Histologic scores showed early OA after ACLT, when compared with the unoperated contralateral side. 846 levels in the synovial fluid lavages of the operated knee joints were increased at all timepoints (p< 0.05) when compared to the non-operated contralateral knees. The highest levels were measured from 2 to 8 weeks with a decrease at 12 weeks. The C2C levels at 4 and 8 weeks were higher than at 2 weeks after ACLT (p< 0.05). Conclusions: To our knowledge, this is the first report of 846 and C2C studied in the same rabbit synovial fluid samples. Both markers have been reported as potential markers of metabolic processes in post-traumatic OA, probably reflecting degrading, respectively rebuilding cartilage processes. Biologically, they might be markers of the ensuing macroscopic and microscopic changes. While the reparative response, as possibly indicated by 846, is not sufficient to stop the destructive process of OA, possibly indicated by C2C, the exact meaning of these marker levels has to be characterised in more detail.
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