Association between changes in molecular biomarkers of cartilage matrix turnover and changes in knee articular cartilage: a longitudinal pilot study

Abstract

Background An early detection of Osteoarthritis is urgently needed and still not possible until today. The aim of the study was to assess whether molecular biomarkers of cartilage turnover are associated with longitudinal change in knee cartilage thickness during a 2 year period in individuals with increased risk of developing knee osteoarthritis. A secondary aim was to assess whether prior knee injury or subjective patient-reported outcomes at baseline (BL) were associated with articular cartilage changes. Nineteen volleyball players (mean age 46.5 ± 4.9 years, 47% male) with a 30-year history of regular high impact training were recruited. The serum biomarkers Cpropeptide of type II procollagen (CPII), cartilage oligomeric matrix protein (COMP), collagenase generated carboxy-terminal neoepitope of type II collagen (sC2C), cartilage intermediate layer protein 2 (CILP-2), and the urine biomarkers C-telopeptide of type II collagen (CTX-II) and collagenase-generated peptide(s) of type II collagen (C2C-HUSA) were assessed at BL and at 2 year follow up (FU). Femorotibial cartilage thinning, thickening and absolute thickness change between BL and FU was evaluated from magnetic resonance imaging. Subjective clinical status at BL was evaluated by the International Knee Documentation Committee Subjective Knee Form and the Short-Form 36 Physical Component Score. Results CILP-2 was significantly higher at FU and linearly associated with the absolute cartilage thickness change during the experimental period. Prior injury was a predictor of increased absolute cartilage thickness change. Conclusion Measuring the change in the cartilage biomarker CILP-2 might be a valid and sensitive method to detect early development of knee osteoarthritis as CILP-2 appears to be related to cartilage thickness loss in certain individuals with increased risk of developing knee osteoarthritis. Prior knee injury may be predictive of increased articular cartilage thickness change.

Membrane-Free Stem Cell Components Inhibit Interleukin-1α-Stimulated Inflammation and Cartilage Degradation In Vitro and In Vivo: A Rat Model of Osteoarthritis

“…In the pathogenesis of OA, IL-1α induces the expression of catabolic enzymes such as MMPs, COMP, and CTX-II that plays a vital role in the degradation of cartilage and also serves as a biomarker of OA [20,21]. First, we investigated the MFSCC-regulated MMPs in IL-1α-stimulated rat primary chondrocytes in vitro.…”

Common Biochemical and Magnetic Resonance Imaging Biomarkers of Early Knee Osteoarthritis and of Exercise/Training in Athletes: A Narrative Review

“…The levels of HA did not vary in marathoners, soccer players, and walkers [47,75]. Increased levels of COMP were reported in marathoners and walkers [52,[66][67][68]75], but remained unchanged in cyclists and volleyball players [53,54]. In soccer players [76,77], training induced fluctuations in the serum COMP levels during a competitive season.…”

“…In contrast, NTX-I, CTX-I, and CTX-II levels were decreased in cyclists [54]. In volleyball players, C2C and CTX-II levels were reported as unchanged [53,59], and C2C levels were unchanged as well in marathoners [52,53].…”

“…Serum levels of the collagen synthesis markers CPII and PIIANP have been reported to decrease in OA [51,62], and the CPII decrease was also observed in situ in OA knee cartilage [81]. There is no report of the effect of exercise on PIIANP levels, but CPII levels were found unchanged in runners, soccer, rugby, and volleyball players [52,53,60].…”

Biomarkers of Joint Damage in Osteoarthritis: Current Status and Future Directions

“…Two more byproducts of collagen breakdown have been identified, which are responsible for cartilage deformity, type II procollagen carboxy-propeptide (CPII), and urinary cterminal crosslinking telopeptide [33]. CPII levels were upregulated in serum and SF in the early stage of OA, while the levels of CPII were found to be downregulated due to chondrocyte failure and cartilage erosion [34].…”