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Evaluation of cartilage damage by measuring collagen degradation products in joint extracts in a traumatic model of osteoarthritis
Authors:Rasmus H Nielsen  Reinout Stoop  Diana J Leeming  Marina Stolina  Per Qvist  Claus Christiansen
Institution:1. Nordic Bioscience, Herlev, Denmark;2. NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany;3. Department of Metabolic Disorders, Amgen Inc, Thousand Oaks, CA, USA
Abstract:The objective of this work was to investigate whether collagen degradation products in protein extract from joints could provide quantitative information on cartilage damage. Osteoarthritis (OA) was surgically induced in rat knee joints. Joints were isolated 7, 14 and 28 days after surgery for protein extraction and histology. C-terminal telopeptide of type II collagen (CTX-II), CTX-I and hydroxyproline were measured in protein extracts. Matrix metalloproteinase (MMP)-2 and -9 activity was evaluated by gelatinase zymography and joint pathology was visualized by histology and immunohistochemistry. The results showed that levels of CTX-II were significantly increased in anterior cruciate ligament transection (ACLT)-operated compared with sham-operated knee joints on days 7 and 28, whereas the levels of hydroxyproline and CTX-I epitopes showed no difference. MMP activity was slightly increased in ACLT-operated joints. The CTX-II epitope was highly expressed and co-localized to damaged articular cartilage in ACLT-operated joints. We have therefore demonstrated an increased type II collagen degradation in knees after surgical induction of OA, and propose assessment of collagen degradation epitopes as a quantitative measure of cartilage damage.
Keywords:Osteoarthritis  anterior cruciate ligament transaction  cartilage damage  protein extraction  CTX-II  CTX-I
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