Effects of EGFR and CCR2 Signaling in Post-Traumatic Osteoarthritis
Abstract
Background: Researchers demonstrated that inhibition of epidermal growth factor receptor (EGFR) and/or its downstream signal transducer, C-C motif chemokine receptor-2 (CCR2) blocked development of post-traumatic Osteoarthritis (PTOA) in rat model if applied from the time of injury. However, it is unclear how effective these drugs are if treatment is initiated after injury, a situation more translatable to the human condition.
Methods: Osteoarthritis (OA) was induced surgically in 4 groups. Treatment was initiated 4-weeks post-surgery where groups were given 50% DMSO solution(vehicle), AG1478(EGFR-blocker), RS504393(CCR2-blocker), and EGFR+CCR2 combinational inhibitor. Rats were sacrificed 7 and 10weeks after surgery. OA was examined histologically by staining the samples with Safranin-O-fast green and hematoxylin & eosin stain for assessing cartilage and synovial damage respectively.
Results: There are no significant differences seen in treated Osteoarthritis Research Society International (OARSI) and synovitis scores vs vehicle group in both timeline rats.
Conclusion: Thus, our results did not support our hypothesis and the described protective effects of these compounds require application at or immediately after injury.
Keywords: Epidermal Growth Factor Receptor, CCR2, CCL2, post-traumatic Osteoarthritis