|Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Articular cartilage has the boundary surfaces such as articular surface, osteochondral junction and synovial-cartilage junction. These boundary surfaces have the peculiar form, and it seems to be the part in which the change occurs in arthrosis and arthritis, etc. first. Since it is contributory to elucidation of pathogenesis of arthropathies and establishment of the therapy, (1) biochemical analysis of articular cartilage most superficial layer, (2) change in the synovial-cartilage junction and destruction of subchondral bone in the arthritis, (3) effect by the drugs of the joint destruction in the arthritis, and (4) gene expression relevant to osteoclastogenesis in the synovium and bone marrow in the arthritis were examined.
(1)The most superficial layer of adult articular cartilage consisted not of type II collagen but of types I and III. This immunohistochemical finding was identical to that of synovial tissue. The results suggested this layer is absolutely independent from its deep
er layer. and that the most superficial layer could be a residue of fibrous tissue derived from the synovial mesenchyme at developmental stage of the joint.
(2)Bone destruction in collagen-induced arthritis (CIA) began with the appearance of tartrate-resistant acid phosphatase, (TRAP)-positive cells on the lateral side of the cortical bone under the synovial-cartilage junction (SCJ), followed by the TRAP-positive multinuclear cells in bone marrow, which were morphologically unconnected to the SCJ lesions. These findings suggested that bone destruction in the early stage of arthritis occurred in two anatomically different regions.
(3)A third-generation bisphosphonate containing nitrogen suppressed the decrease in bone mineral density (BMD) and deterioration of the bone microstructure caused by CIA. The prophylactic administration of this bisphosphonate had more preventive effect against arthritis at the early 'stage, not throughout the observation period, than the therapeutic administration. Intermittent PTH administration activated bone formation, resulting in increased BMD and preventing deterioration of mechanical properties. PTH had no effect on arthritis.
(4) In the early stages of CIA, synovial RANKL was closely involved in osteoclastogenesis, and various changes in synovial cytokines, including down-regulation of OPG, probably accelerated osteoclast formation. In contrast, cytokine mRNA in the bone marrow showed little fluctuation. The results' suggested that synovial' cytokines affect osteoclastogenesis not only in the synovium but in the bone marrow. Less