Cruciate ligament laxity and femoral intercondylar notch narrowing in early-stage knee osteoarthritis

Arthritis Rheum. 2005 Oct;52(10):3100-9. doi: 10.1002/art.21340.


Objective: The influence of the cruciate ligaments in spontaneous osteoarthritis (OA) is not understood, although ligament rupture is known to cause secondary OA. Additionally, femoral notch narrowing at the anterior cruciate ligament (ACL) insertion site is associated with disease severity, but it is unknown whether ligament deterioration precedes or follows osteophyte formation. We examined cruciate ligament mechanics and metabolism and the intercondylar notch width in OA-prone Dunkin-Hartley (DH) guinea pigs at ages up to and including the age at OA onset (24 weeks), and compared the data with those in age-matched controls (Bristol strain 2 [BS2] guinea pigs).

Methods: Guinea pigs were assessed at 3, 6, 9, 12, 16, 20, 24, and 36 weeks of age. ACLs were mechanically tested, and the intercondylar notch width index (NWI) was determined. Cruciate ligament metabolism was determined by measuring the following markers of collagen turnover: matrix metalloproteinase 2 (MMP-2), tissue inhibitor of metalloproteinases 2, C-terminal type I procollagen propeptide (PICP), and the immature collagen-derived crosslink dihydroxylysinonorleucine (DHLNL).

Results: DH guinea pigs had significantly laxer ACLs than did BS2 guinea pigs, at 12, 16, and 24 weeks. We observed elevated levels of pro and active MMP-2, PICP, and DHLNL in the cruciate ligaments of DH animals at most ages, compared with BS2 guinea pigs. The NWI in DH animals was significantly lower than that in BS2 guinea pigs at 24 and 36 weeks.

Conclusion: In DH guinea pigs, laxer ACLs, which are associated with increased collagen turnover, may cause joint instability and predispose these animals to the early onset of OA. Decreased intercondylar notch width in the DH animals indicates that bone remodeling at the ACL insertion site is a response to elevated ACL laxity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anterior Cruciate Ligament / metabolism
  • Anterior Cruciate Ligament / pathology*
  • Anterior Cruciate Ligament / physiology
  • Biomarkers / metabolism
  • Biomechanical Phenomena
  • Collagen Type I / metabolism
  • Cross-Linking Reagents / metabolism
  • Femur / pathology*
  • Femur / physiology
  • Guinea Pigs
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Osteoarthritis, Knee / metabolism
  • Osteoarthritis, Knee / pathology*
  • Osteoarthritis, Knee / physiopathology
  • Peptide Fragments / metabolism
  • Procollagen / metabolism
  • Severity of Illness Index
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism


  • Biomarkers
  • Collagen Type I
  • Cross-Linking Reagents
  • Peptide Fragments
  • Procollagen
  • procollagen type I carboxy terminal peptide
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2