Benvenuti ad Adobe GoLive 6

Chondrocyte-mediated collagenolysis correlates with cartilage destruction grades in osteoarthritis

Y.T. Konttinen^1,2,3, J. Ma⁴, P. Ruuttila¹, M. Hukkanen², S. Santavirta⁵

¹Department of Medicine, Helsinki University Central Hospital; ²ORTON Orthopaedic Hospital of the Invalid Foundation, Helsinki, Finland; ³COXA The Joint Replacement Hospital, Tampere, Finland; ⁴Anatomy, Biomedicum Helsinki, Helsinki University, Helsinki, Finland; ⁵Orthopaedics and Traumatology Department, Helsinki University Hospital, Finland.

ABSTRACT
Objective
Osteoarthritis (OA) is associated with destruction of type II collagen-rich hyaline articular cartilage. We hypothesized that classical interstitial collagenases cleave collagen type II, leading to the increased expression of the 3/4 native type II collagen fragment (COL2-3/4C) and the corresponding denatured type II collagen fragment (COL2-3/4M), which could correlate with different cartilage destruction grades. In addition, we assessed whether these fragments could be measured in joint fluid and serve as diagnostic markers.

Method
Cartilage specimens were obtained from the femoral heads of hip joints from total hip replacement operations. Articular gliding surfaces of the cartilage were categorized into normal (G0), fibrillated (G1), superficially fissured (G2) and deeply fissured (fissures that reach to the subchondral bone) (G3). A histological scoring of the cartilage was also used. COL2-3/4C and COL2-3/4M were detected by immunohistochemical staining. Dot blotting was used to detect these fragments in joint fluid.

Results
COL2-3/4C and COL2-3/4M were found in the perichondrocyte matrix around lacunae. Such COL2-3/4C (p < 0.05) and COL2-3/4M (p < 0.05) immunoreactivity was significantly increased in G3 and G2 compared to G0 and G1. A positive correlation (n = 35, Spearman rank correlation) was observed between the histological score and the percentage of COL2-3/4C positive lacunae (r = 0.43, p = 0.01) and COL2-3/4M positive lacunae (r = 0.53, p = 0.001). All 7/7 joint fluid samples contained COL2-3/4C in dot blots whereas only 4/7 contained COL2-3/4M.

Conclusion
Collagenase-cleaved collagen \endash both native and denatured - increases as the severity of OA increases, assessed using a macroscopic clinical and microscopic histological grading system. Collagen degradation was always most apparent around chondrocytes. Further
more, the native COL2-3/4C fragment has potential as a joint fluid marker for OA.

Key words
Collagenase, collagen type II, osteoarthritis, pannus.

This study was supported by grants from the Finska Läkaresällskapet, the Sigrid Juselius Foundation, the Willhelm and Else Stockmann Foundation, the National Technology Agency of Finland (TEKES), the University of Helsinki, the Academy of Finland and Clinical EVO Research Grants (TYH1202, TYH0215 and TKIO601).
Please address correspondence to: Yrjö T. Konttinen, MD, PhD, Biomedicum Helsinki, P. O. Box 700 (Haartmanin-katu 8), FIN-00029 Helsinki University Central Hospital, Finland.
E-mail: yrjo.konttinen@helsinki.fi