Although adult human cartilage is physiologically avascular tissue, angiogenesis can be observed during the process of endochondral bone development. Inflammation in articular joints can also lead to ...neovascularization in cartilage. In such conditions, the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF), has been shown to play a key role, controlling not only angiogenesis but also chondrocyte metabolism. Here we review recent research findings concerning the potential role of VEGF in cartilage, focusing in particular on its possible involvement in the pathogenesis of osteoarthritis.
Objective: To determine whether IL18 has any indirect effects on osteoclastogenesis mediated by T cells in RA synovium, and compare its effects with those of IL1β and TNFα. Methods: Resting T cells ...were isolated from peripheral blood of healthy donors, and stimulated with 2 μg/ml phytohaemagglutinin (PHA) and 0.5 ng/ml IL2 for 24 hours. Synovial T cells were isolated from RA synovial tissue. The levels of soluble receptor activator of the NF-κB ligand (RANKL), osteoprotegerin (OPG), IFNγ, M-CSF, and GM-CSF were determined by ELISA. Membrane bound RANKL expression was analysed by flow cytometry. Commercially available human osteoclast precursors were cocultured with T cells to induce osteoclast formation, which was determined with tartrate resistant acid phosphatase staining and pit formation assay. Results: In PHA prestimulated T cells or RA synovial T cells, IL18, IL1β, or TNFα increased soluble RANKL production and membrane bound RANKL expression in a dose dependent manner. IL18, IL1β, and TNFα did not induce M-CSF, GM-CSF, IFNγ, or OPG production in PHA prestimulated T cells or RA synovial T cells. IL18 increased the number of osteoclasts and bone resorption area on dentine slices in the coculture of human osteoclast precursors with PHA prestimulated T cells or RA synovial T cells; its ability was equivalent to that of IL1β, but less potent than that of TNFα. In the coculture system, OPG completely blocked osteoclast induction by IL18 or IL1β, and greatly inhibited induction by TNFα. Conclusion: IL18, IL1β, or TNFα can indirectly stimulate osteoclast formation through up regulation of RANKL production from T cells in RA synovitis; IL18 is as effective as IL1β, but less potent than TNFα.
The vascular invasion of bone marrow tissue into the subchondral plate is often observed in articular cartilage and we named it the subchondral bone absorption pit; however, its implication in the ...pathogenesis of osteoarthritis (OA) has been poorly understood. The purpose of this study was to evaluate its characteristics and roles in osteoarthritic conditions.
Articular cartilage specimens from 11 patients with medial type knee OA and 7 non-arthritic cadavers were analyzed with HE staining. OA sections were stained with safranin-O, TRAP (tartrate resistant acid phosphatase) and immunostained with anti-MMP-1, MMP-3, MMP-13, vitronectin receptor (VNR)-α chain, vimentin and bone morphogenic protein (BMP) 2/4 antibodies.
Subchondral bone resorption pits were classified according to the extent of invasion: pits with bone marrow tissue were located within uncalcified cartilage below the tidemark in grade I and invaded beyond the tidemark in grade II, while no invasion was seen in grade 0. Grade II pits were dominant in OA compared to non-arthritic joints, especially medial condyles. Proteoglycan detected with safranin-O staining was lost around the tip of grade II pits and the density of pits was related to the modified Mankin Score. Cells in pits expressed vimentin, MMP-1, MMP-3 and MMP-13. Some polynuclear cells co-expressed VNR-α chain and MMP-13, whereas pits showed reparative features expressing BMP.
These results suggest that subchondral bone resorption pits contribute to cartilage degradation by expressing matrix metalloproteinases in OA.
Osteoarthritis (OA) is considered to be linked to obesity and body fat mass. Recent investigations, however, are aimed at clarifying the roles of adipose tissue-derived proteins and a wide variety of ...lipid mediators, including fatty acids, sphingolipids, and eicosanoids, in cartilage degradation in OA, in addition to the effects body weight itself. Here, we review recent progress in studies of OA, focusing on the potential role of lipid mediators in articular cartilage and introducing the concept that "OA is a metabolic disease" in which lipids essentially contribute to the pathophysiology of cartilage degradation.
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