The present results suggest that activated RASF, by expressing ODF, play an important role in rheumatoid bone destruction. Moreover, the data provide evidence that RASF not only activate osteoclasts, but also contribute directly to osteoclastogenesis.

Our results indicate a role for MT1-MMP not only in the matrix degradation by fibroblasts, but also in osteoclast-mediated bone resorption in RA. Given the ability of MT1-MMP to activate MMP-2 and MMP-13, the findings also point to a cooperation between fibroblasts and macrophages in degrading cartilage and bone. While MT3-MMP is also intensely expressed in RA synovium, MT2- and MT4-MMP appear not to be involved in rheumatoid joint destruction.

Objective. Sentrin, a novel antiapoptotic molecule, has been shown to interact with the signalcompetent form of Fas/APO-1 and tumor necrosis factor receptor I (TNFRI), and thereby, to protect cells against anti-Fas/APO-1-and TNF-induced cell death. Since reduced apoptosis in the synovial lining is supposed to contribute to synovial hyperplasia in rheumatoid arthritis (RA), we searched for the expression of sentrin-1 messenger RNA (mRNA) in synovium from patients with RA.Methods. The expression of sentrin-1 mRNA was examined by in situ hybridization on snap-frozen sections of normal and RA synovial tissues as well as on paraffin-embedded RA synovial specimens, including the interface of cartilage-bone and invading synovium. Immunohistochemical double labeling after in situ hybridization was performed to further characterize sentrin-1 mRNA-expressing cells. In addition, quantitative analysis of sentrin-1 mRNA expression in RA synovial fibroblasts (RASF), osteoarthritis synovial fibroblasts (OASF), and normal fibroblasts was performed by quantitative real-time polymerase chain reaction. Expression levels were standardized to the expression of GAPDH. The in vivo maintenance of sentrin expression in RASF aggressively invading human cartilage was explored in the SCID mouse model of RA.Results. A marked expression of sentrin-1 mRNA could be seen in all RA synovial specimens, predominantly in SF of the lining layer and at sites of invasion of RA synovium into cartilage. In normal synovial tissues, no sentrin-1 mRNA was detectable. RASF showed a maximum 32.5-fold (mean ؎ SD 14.9 ؎ 11.6) increase of sentrin-1 mRNA expression compared with normal fibroblasts and a maximum 31.4-fold (mean ؎ SD 14.3 ؎ 10.9) increase compared with OASF. When coimplanted with normal human cartilage in the SCID mouse model, invading RASF maintained their sentrin-1 mRNA expression for at least 60 days in vivo.

We treated 31 patients with non-traumatic paralysis of the posterior interosseous nerve over 15 years. There were 10 men and 21 women of mean age 40.3 years (17 to 71). Six were managed conservatively, and 25 by operation. In 14 patients entrapment occurred at the supinator, including three who had double compression at both the entrance and exit from the muscle. In four it was caused by a ganglion, in one by a lipoma, in one by a dislocated radial head and in two by a marked constriction in the nerve of unknown cause. The remaining three patients were retrospectively diagnosed as having neuralgic amyotrophy, the only observable change at operation being slight oedema of the nerve. Paralysis recovered in 24 out of the 25 patients at between 2 to 18 months (mean 5.6) after operation, and the one failure was treated later by tendon transfer.

Conclusion. The data demonstrate that an antisense RNA expression construct against MT1-MMP can be generated and expressed in RASFs for at least 60 days. Inhibition of MT1-MMP significantly reduces the cartilage degradation by RASFs.Membrane-type matrix metalloproteinases (MTMMPs) are cell membrane-anchored MMPs that have been associated with both normal tissue remodeling and various diseases. Six different MT-MMPs have thus far been described, of which membrane type 1 MMP (MT1-MMP) has been studied most intensively. MT1-MMP (also called MMP-14) has a specific structural organization that is characterized by a hydrophobic transmembrane domain and a short cytoplasmic tail. It also contains a recognition site for furin-like proprotein convertases, which, by furin-dependent cleavage, activate MT1-MMP intracellularly (1). MT1-MMP digests interstitial collagens as well as other extracellular matrix components, including fibronectin, laminin, aggrecan,