Changes in the Integrins Expression Are Related With the Osteoarthritis Severity in an Experimental Animal Model in Rats

We identify changes in the expression and localization of alpha 5, alpha 4, and alpha 2 integrins during osteoarthritis (OA) pathogenesis in a rat experimental model. The changes were concomitant with variations in the extracellular matrix (ECM) content and the increase of metalloproteinases (MMPs) activity during OA pathogenesis, which were analyzed by immunofluorescence and Western blot assays. Our results showed an increased expression of alpha 5 and alpha 2 integrins at OA late stages, which was co-related with changes in the ECM content, as a consequence of the MMPs activity. In addition, this is the first report that has shown the presence of alpha 4 integrin since OA early stages, which was co-related with the loss of proteoglycans and clusters formation. However, at late OA stages, the increased expression of alpha 4 integrin in the middle and deep zones of the cartilage was also co-related with the abnormal endochondral ossification of the cartilage through its interaction with osteopontin. Finally, we conclude that ECM-chondrocytes interaction through specific cell receptors is essential to maintain the cartilage homeostasis. However, due to integrins cell signaling is ligand-dependent; changes in the ECM contents could induce activation of either anabolic or catabolic processes, which limits the reparative capacity of chondrocytes, favoring OA severity. (C) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.