Atrophic myotubes presented molecular characteristics that are typically observed 
following DUX4 expression. Conversely, disorganized myotubes presented increased Lomitapide Mesylate levels of proteins involved in microtubule network organization and myofibrillar remodeling, which suggests a compensatory response to DUX4-mediated damage. Further studies are necessary to determine the relative contribution of other 4q35 genes leading to this phenotype. Moreover, our results suggest that FSHD pathogenesis could partially involve a defect of membrane microdomains as observed in other neuromuscular disorders. Finally, the study of a fraction enriched in nuclear proteins suggested a defect in RNA processing in FSHD myotubes. The temporo-mandibular joint disc is a fibrocartilaginous tissue that lies between the mandibular condyle and the temporal fossa-eminence. Several disorders may affect the TMJ disc, including intra-articular positional and structural abnormalities with high prevalence in adult populations, especially TMJ degenerative diseases, known as osteoarthrosis or osteoarthritis. Butenafine hydrochloride clinical management of the most prevalent TMJ disc disorders is very challenging due to the low regeneration capability of human cartilage, and emerging therapies based on cultured human TMJF and tissue engineering represent a novel treatment possibility. The TMJ disc is mainly composed by fibrochondrocytes, which have features of both chondrocytes and fibroblasts. Human TMJF are known to have the capability to synthetize different fibrillar extracellular matrix constituents, mainly collagen, and several non-fibrillar components, and to proliferate faster than hyaline chondrocytes. The distribution of TMJF into the disc appears to be heterogeneous, and cells tend to show a round morphology surrounded by pericellular matrix. Several efforts are currently ongoing in the field of TMJ disc tissue engineering using an immense variety of scaffolds and cell sources. Nevertheless, the scarce number of cells that can be obtained from small TMJ disc tissue biopsies and the drop of cell viability and cell differentiation levels caused by continuous cell passaging in order to obtain large amounts of cells, are significant limitations associated to TMJF culturing and TMJ disc tissue engineering. All these limitations can result in the failure of cell therapy and tissue engineering strategies of the human TMJ disc repair. For these reasons, a deep study of sequential cell passages of cultured human TMJF might be a useful tool for tissue engineers in order to select the most suitable cell passage in terms of cell viability and differentiation from a clinical standpoint. In fact, several previous studies previously demonstrated that cell viability may vary among several cell passages and that selection of the most adequate cell passage is very important for cell therapy success. In this study, we carried out a comprehensive analysis of cell proliferation, cell viability and cell function on 9 consecutive cell passages of human TMJF to determine which passage is the most adequate for future clinical use. A therapeutic advance in the treatment of TMJ pathological conditions could be the generation of biological substitutes of damaged discs generated by tissue engineering. Different models of engineered TMJ disc have been developed by using animal cells and different biomaterials and signaling. In most of these studies, the key importance of an accurate cell viability determination has been established, since only viable cells should be used for TMJ disc tissue engineering.