Reduced EGFR signaling enhances cartilage destruction in a mouse osteoarthritis model

Osteoarthritis （OA） is a degenerative joint disease and a major cause of pain and disability in older adults. We have previously identified epidermal growth factor receptor （EGFR） signaling as an important regulator of cartilage matrix degradation during epiphyseal cartilage development. To study its function in OA progression, we performed surgical destabilization of the medial meniscus （DMM） to induce OA in two mouse models with reduced EGFR activity, one with genetic modification （, was/＋ mice） and the other one with pharmacological inhibition （gefitinib treatment）. Histological analyses and scoring at 3 months post-surgery revealed increased cartilage destruction and accelerated OA progression in both mouse models. TUNEL staining demonstrated that EGFR signaling protects chondrocytes from OA-induced apoptosis, which was further confirmed in primary chondrocyte culture. Immunohistochemistry showed increased aggrecan degradation in these mouse models, which coincides with elevated amounts of ADAMTS5 and matrix metalloproteinase 13 （MMP13）, the principle proteinases responsible for aggrecan degradation, in the articular cartilage after DMM surgery. Furthermore, hypoxia-inducible factor 2α （HIF2α）, a critical catabolic transcription factor stimulating MMP13 expression during OA, was also upregulated in mice with reduced EGFR signaling. Taken together, our findings demonstrate a primarily protective role of EGFR during OA progression by regulating chondrocyte survival and cartilage degradation.

How to establish an expected animal model of post-traumatic osteoarthritis?

Background：Animal models of osteoarthritis（OA）,including post-traumatic osteoarthritis and spontaneous osteoarthritis,have been established in many ways.In recent years,there have been many reports in various foreign academic journals,but animal models of post-traumatic osteoarthritis（distinct from spontaneous osteoarthritis） have rarely been established or summarized in these reports.Animal models of post-traumatic osteoarthritis show different characteristics depending on the animal species and modeling methods used,which is why we have written this article.Objective：To summarize the research progress and research status of animal models of post-traumatic osteoarthritis.Methods：A retrospective review of the animal model of post-traumatic osteoarthritis（OA） was conducted on the basis of reports retrieved from the PubMed database with the keywords for searching ＂animal model,post-traumatic osteoarthritis（PTOA）＂ from October 2006 to October 2016 and confided English language.A total of 80 academic articles on the study of animal models of traumatic osteoarthritis were retrieved,and 34 of them were included in this literature review after reading the free fulltext of them.Results：Different PTOA models based on different modeling methods and different animal species had their own characteristics.Different modeling methods should be selected according to different modeling animals.Conclusions：Considering the project funds,experimental objectives and technical conditions,appropriate experimental animal and modeling method should be selected based on synthetic considerations to obtain an appropriate PTOA model and ideal experimental results.