The biochemical mechanism for initiation of cartilage destruction in osteoarthritis (OA) is unknown but may involve as yet unidentified cartilage genes. The first evidence that MIG-6, a protein involved in signal transduction, is expressed in articular cartilage came from our recent in vitro microarray experiments using the Affymetrix canine GeneChip. Quantitative RT-PCR (q RT-PCR) confirmed a fourfold increase in MIG-6 mRNA in cartilage in response to mechanical impact ill vitro. Our goal is to determine if MIG-6, which responds to mechanical impact, could have a role in the initiation of OA. We determined that mRNA transcript levels of MIG-6 were fourfold higher in degenerated cartilage from dogs with hip osteoarthritis than in disease-free cartilage from unaffected dogs and twofold higher than in the cartilage surrounding the lesion. This is the first report associating MIG-6 with OA. Additional studies will determine what role MIG-6 has in the origin of cartilage degeneration. (C) 2005 Elsevier Inc. All rights reserved.