The extent of degeneration of cruciate ligament is associated with chondrogenic differentiation in patients with osteoarthritis of the knee

Abstract

Degeneration in cruciate ligaments results from abnormal biomechanical stress and the aging process. Such degeneration is a common outcome in patients with osteoarthritis (OA) of the knee and contributes to the progression of OA. However, to date, there are no specific markers that can predict the extent of ligament degeneration. We hypothesized that the extent of degeneration has correlations to increased chondrogenic potential. Twenty anterior cruciate ligaments (ACLs) and 30 posterior cruciate ligaments (PCLs) from 30 knees of 28 adult patients with OA at the time of total knee arthroplasty were used for the study. Degeneration was histologically assessed using a grading system. Expressions of Scleraxis (as a ligament cell marker) and Sry-type HMG box 9 (SOX9) (as a chondrogenic marker) were immunohistochemically assessed in each grade. We found the opposite expression pattern between Scleraxis and SOX9 according to the grade. The percentage of Scleraxis-positive cells decreased significantly by grade (60.9±23.7 in grade 1, 39.7±30.5 in grade 2, and 13.9±27.1 in grade 3, P<0.0001). In contrast, the percentage of SOX9-positive cells increased significantly by grade (2.5±4.9 in grade 1, 17.5±13.4 in grade 2, and 50.9±27.1 in grade 3, P<0.0001). Furthermore, co-localized expression of both Scleraxis and SOX9 was demonstrated in chondrocyte-like cells. This study indicates that chondrogenic differentiation is associated with the progression of degeneration in human ligaments. Our results suggest that the expression of SOX9 as a chondrogenic marker could be an indicator for the extent of degeneration in human ligaments. It remains to be elucidated whether suppression of chondrogenic differentiation can prevent progression of the degenerative process of cruciate ligaments in patients with OA.