Trauma and disease of joints frequently involve structural damage of the articular cartilage. These pathologies result in severe pain and disability for millions of people world-wide and represent a major challenge for the orthopaedic community. Cellular therapy and tissue engineering are promising strategies for the repair of such defects. These approaches currently rely on the use of autologous articular chondrocytes (AC), harvested from a small articular cartilage biopsy. As compared to AC, nasal chondrocytes (NC) have been shown to have a higher and more reproducible chondrogenic capacity, thus their clinical utilization would improve the clinical outcome. However, the different embryologic origin of AC and NC (neuroectodermal and mesodermal, respectively), could represent a limit. This study generally addresses the suitability of NC for articular cartilage repair. In particular, modification of the expression of developmentally related HOX genes by NC under controlled conditions will be studied since these genes are supposed to be critical determinants for graft integration into new locations. The working hypothesis of the proposed research is that de-differentiated nasal chondrocytes, by displaying a large degree of plasticity, are compatible with articular joint implantation. The plasticity is defined by the capacity of nasal chondrocytes to (i) exhibit multipotential differentiation capacity -even at clonal levels, (ii) modify their original HOX gene expression status acquiring a pattern closer to that of articular chondrocytes under culture conditions mimicking the natural joint environment and (iii) promote cartilage repair following orthotopic implantation in articular defects created in goats. The proposed research will acquire crucial information about the biology of nasal chondrocytes and their response to specific in vitro conditions mimicking the articular joint environment. Moreover it will provide the necessary pre-clinical data for the potential use of nasal chondrocytes as a cell source for the repair of joint cartilage lesions. Finally, the analysis of the modulation of HOX genes in our cell culture system will represent a first step towards bringing together two traditionally separated disciplines, namely regenerative medicine and developmental biology.