Evaluation of cartilage damage by measuring collagen degradation products in joint extracts in a traumatic model of osteoarthritis

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 III 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.

Regulation of the inflammatory response by tin protoporphyrin IX in the rat anterior cruciate ligament transection model of osteoarthritis

“…The development of cartilage degeneration follows mechanical overloading of the surface of cartilage and it is associated with localized destruction of the type II collagen network 5. In fact, the CTX‐II epitope has been shown to be highly expressed and co‐localized to damaged articular cartilage in ACLT‐operated rat joints 23. Our results confirm the interest of serum CTX‐II as a biomarker of disease progression in this OA animal model.…”

Matrix metalloproteinase-9-mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis

“…CTX‐I is a bone resorption marker in both simple in vitro systems, preclinical animal models and in clinical trials, where it rapidly and sensitively monitors bone resorption (11, 36). CTX‐II is generated by MMP activity during cartilage degradation, occurring as a result of both inflammatory arthritis and osteoarthritis (37, 38). CTX‐II levels have been shown to predict joint space narrowing and loss of cartilage volume (27–29).…”

Lessons Learned From the Development of Oral Calcitonin: The First Tablet Formulation of a Protein in Phase III Clinical Trials

“…42,44 During cartilage degradation, CTX-II is generated by the matrix metalloproteinase activity that occurs in inflammatory arthritis and osteoarthritis. 45,46 Raised CTX-II levels have been shown to predict joint space narrowing and loss of cartilage volume. [47][48][49]…”