Aseptic prosthesis loosening (APL) is an active process that is linked to the development of a synovial-like interface membrane (SLIM) at the bone-implant interface. Growing evidence suggests that the synovial membrane in rheumatoid arthritis (RA) and this SLIM share certain similarities. However, the mechanisms of SLIM formation as well as the cellular and molecular events in the activation of fibroblast-like cells remain elusive. Recently, we have established a novel animal model of SLIM formation that is based on the implantation of joint arthroplasties into intracranially self-stimulated (ICSS) Wistar rats. Data from this animal model as well as from human SLIM samples suggest that there is a subset of activated fibroblast-like cells present also in the SLIM of APL. These prosthesis-loosening fibroblasts (PLF) not only show a similar growth pattern as RA-synovial fibroblasts (RA-SF) but also exhibit features of cellular activation found in RA. Among them, the up regulation of transcription factors and the resistance against Fas-induced apoptosis are most prominent. Although PLF express a number of matrix degrading enzymes and secrete soluble factors that stimulate neighbouring cells, their role in the degradation of bone has been restricted to that of supporting bystanders. Based on most recent results, we report that PLF from the SLIM around loose joint prostheses display a highly aggressive, RA-like phenotype when implanted into SCID mice, are capable of resorbing bone in vivo without the help of osteoclasts and release large amounts of acidic components. As demonstrated by RT-PCR, in situ hybridization and immuno electron microscopy, these cells express a specific proton pump (v-ATPase) on their cell surface that may account for their ability to decalcify bone. By quantitative real time PCR, an increased expression of this v-ATPase is found in prosthesis loosening fibroblasts and rheumatoid synovial fibroblasts as compared to normal or osteoarthritic cells. Inhibition of the v-ATPase with specific inhibitors results in a decrease of pericellular acidification. Investigating the exon structure of its catalytic β1 subunit, we were able to describe a hitherto unknown v-ATPase splice variant that appears to be regulated differently in prosthesis loosening fibroblasts as compared to rheumatoid and osteoarthritic cells. The expression of specific v–ATPases on their cell membranes including novel splice variants may provide the means by which these cells are able to decalcify bone prior to its degradation. Further studies will have to clarify whether the capability of PLF to resorb bone constitutes a rather unique feature of these cells or is linked also to cellular activation in RA.
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