| dc.description.abstract | Joint injures frequently involve structural damage to articular cartilage and the underlying subchondral bone. The outcome of acute joint surface defects (JSD) varies from spontaneous healing to the development of post-traumatic osteoarthritis (PTOA). The cellular and molecular mechanisms regulating joint surface repair are still unknown and failure of these reparative mechanisms could be a contributing factor for PTOA development. The absence of animal models suitable for molecular functional studies in cartilage regeneration has so far represented a bottleneck for the research in this field.
In this study we have generated a mouse model of joint surface injury which, in a strain- and age-dependent manner results either in spontaneous healing in the DBA/1 strain or in PTOA in C57BL/6 strain. The healing outcome in DBA/1 mice was associated with progressive decline of chondrocyte apoptosis, cell proliferation within the repair tissue, persistent type II collagen neo-deposition, less type II collagen degradation, and aggrecan degradation predominantly driven by metalloproteinases, with minor aggrecanase activity. Furthermore, we have demonstrated that mechanical injury to articular cartilage in vitro and in vivo results in activation of a signalling response with reactivation of morphogenetic pathways such as BMP and Wnt. Notably, we have observed a striking up-regulation of Wnt16 following cartilage injury and in osteoarthritis and showed that this molecule might have a chondro-protective role in murine osteoarthritis. The in vivo model of JSD, being amenable to genetic manipulation, offers the opportunity to investigate the function of different candidate molecules modulated in response to injury which is an essential prerequisite to develop novel molecular therapeutics to support joint surface healing and to prevent possible evolution of PTOA. | en_US |
