Cathepsin K deficiency partially inhibits, but does not prevent, bone destruction in human tumor necrosis factor-transgenic mice.

Objective: Cathepsin K is believed to have an eminent role in the pathologic resorption of bone. However, several studies have shown that other proteinases also participate in this process. In order to clarify the contribution of cathepsin K to the destruction of arthritic bone, we applied the human tumor necrosis factor (hTNF)-transgenic mouse model, in which severe polyarthritis characterized by strong osteoclast-mediated bone destruction develops spontaneously.

Cooperation of Ras- and c-Myc-dependent pathways in regulating the growth and invasiveness of synovial fibroblasts in rheumatoid arthritis.

Objective: To study the specific contribution of MAP kinase activator c-Raf-1 and one of its downstream transcription factors, c-Myc, to the growth and invasive behavior of rheumatoid arthritis synovial fibroblasts (RASFs).

Methods: RASFs were transduced with retroviral constructs expressing dominant-negative mutants of c-Raf-1 or c-Myc (DN c-Raf-1 or DN c-Myc, respectively) or with the mock vector. The expression of wild-type and mutant proteins was confirmed by Western blotting.

Proinflammatory role of fractalkine (CX3CL1) in rheumatoid arthritis.

Objective: Fractalkine (CX3CL1) represents the sole member of the so-called CX3C chemokines. In rheumatoid arthritis (RA), functional studies suggest a role for this chemokine in monocyte chemotaxis and angiogenesis in the rheumatoid synovium. We analyzed the expression of fractalkine within different T cell subsets of the peripheral blood and expression of its receptor CX3CR1 within the rheumatoid synovium to further characterize its pathogenic role in RA.

Functional characterization of adherent synovial fluid cells in rheumatoid arthritis: destructive potential in vitro and in vivo.

Objective: To characterize the morphologic and immunologic features of adherent synovial fluid cells derived from patients with rheumatoid arthritis (RA), and to explore their potential function in vitro and in vivo by focusing on cartilage destruction.

Methods: Synovial fluid adherent cells obtained from patients with RA and from control subjects were characterized by immunohistochemistry, flow cytometry, and electron microscopy. In vitro, these cells were cultured in the presence of cartilage particles.

Expression of activation-induced, T cell-derived, and chemokine-related cytokine/lymphotactin and its functional role in rheumatoid arthritis.

Objective: To evaluate the possible role of activation-induced, T cell-derived, and chemokine-related cytokine (ATAC)/lymphotactin (Lptn) in the pathogenesis of rheumatoid arthritis (RA).

Methods: ATAC/Lptn levels in serum and synovial fluid samples were measured by sandwich enzyme-linked immunosorbent assay. Expression of messenger RNA for ATAC/Lptn in synovial tissues was analyzed by reverse transcription-polymerase chain reaction (PCR) and by in situ hybridization, and was quantitated by real-time PCR.

Osteoclast-independent bone resorption by fibroblast-like cells.

To date, mesenchymal cells have only been associated with bone resorption indirectly, and it has been hypothesized that the degradation of bone is associated exclusively with specific functions of osteoclasts. Here we show, in aseptic prosthesis loosening, that aggressive fibroblasts at the bone surface actively contribute to bone resorption and that this is independent of osteoclasts. In two separate models (a severe combined immunodeficient mouse coimplantation model and a dentin pit formation assay), these cells produce signs of bone resorption that are similar to those in early osteoclastic resorption.

[Metformin-associated lactic acidosis with acute renal failure in type 2 diabetes mellitus].

Case Report: An 83-year-old patient was admitted to our hospital because of gastrointestinal symptoms, mental confusion and dysarthria. The patient suffered from type 2 diabetes mellitus and was taking metformin. A mild renal insufficiency was known.