Joint Hemorrhage Accelerates Cartilage Degeneration in a Rat Immobilized Knee Model
Abstract Background: Joint hemorrhage is caused by trauma, ligament reconstruction surgery, and bleeding disorder such as hemophilia. Recurrence of hemorrhage in the joint space induces hemosiderotic synovitis as well as oxidative stress, resulting in both articular cartilage degeneration and arthropathy. Joint immobilization is a common treatment option for articular fractures accompanied by joint hemorrhage. Although it is apparent that joint hemorrhage is harmful on the articular cartilage, there was no consensus whether reduction of joint hemorrhage is effective to prevent articular cartilage degeneration. The purpose of this study was to investigate the articular cartilage degeneration induced by a combination of joint hemorrhage and joint immobilization in a rat knee model.Methods: The knee joints of adult male rats were immobilized at the flexion using an internal fixator from 3 days to 8 weeks. The rats were divided randomly into two groups: immobilized blood injection (Im-B) group and immobilized-normal saline injection (Im-NS) group. The cartilage was evaluated at two areas (contact and non-contact areas). The cartilage was assessed for the chondrocyte count, Modified Mankin score, and cartilage thickness. Total RNA was extracted from the cartilage in both areas, and gene expressions of metalloproteinase (MMP)-8, MMP-13, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α were measured by quantitative real-time polymerase chain reaction.Results: The number of chondrocytes in the Im-B group significantly decreased in both areas, compared to the Im-NS group. Modified Mankin score from 4–8 weeks of the Im-B group was significantly greater than the Im-NS group only in the contact area. Gene expressions of MMP-8 and MMP-13 from 2–4 weeks and TNF-α from 2–8 weeks significantly increased in the Im-B group compared to the Im-NS group, while there was no significant difference in IL-1β.Conclusions: This study showed that joint hemorrhage exacerbated immobilization-induced articular cartilage degeneration. Therefore, drainage of a joint hemorrhage and avoidance of loading are recommended to prevent cartilage degeneration during immobilization of a joint hemorrhage.