Estrogen reduces mechanical injury-related cell death and proteoglycan degradation in mature articular cartilage independent of the presence of the superficial zone tissue

Objective: To study the effect of 17 beta-estradiol (E2) and the superficial zone (SFZ) on cell death and proteoglycan degradation in articular cartilage after a single injurious compression in vitro. Method: Cartilage explants from the femoropatellar groove of 2 year old cows with or without the SFZ were cultured serum-free with physiological concentrations of E2 and injured by an unconfined single load compression (strain 50%, velocity 2 mm/s). After 96 h cell death was measured histomorphometrically (nuclear blebbing (NB) and TUNEL staining) and release of glycosaminoglycans (GAG) by DMMB assay. Results: Injurious compression increased significantly the number of cells with NB and TUNEL staining and release of GAG. Physiological concentrations of E2 prevented the injury-related cell death and reduced the GAG release significantly in a receptor-mediated manner (shown by co-stimulation with the antiestrogen fulvestrant/faslodex/ICI-182,780). The presence of the SFZ did not alter the NB response to either the mechanical injury or E2, but reduced the overall release of GAG significantly. Conclusion: E2 prevents injury-related cell death and GAG release, and might be useful for the development of treatment options for either cartilage-related sports injuries or osteoarthritis (OA). The SFZ does not seem to play an important role in (1) the E2-related tissue response and (2) the mechanicallyinduced cell death in deeper regions of the explants and GAG release. The latter might be related to the unconfined nature of the injury model. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.