| Co-Investigator(Kenkyū-buntansha) |
ISHIGURO Naoki Nagoya University School of Medicine, Assistant Prof., 医学部, 助手 (20212871)
HASEGAWA Yukiharu Nagoya University School of Medicine, Lecturer, 医学部, 講師 (50208500)
SATO Keiji Nagoya University School of Medicine, Lecturer, 医学部, 講師 (20178726)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1992: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Research Abstract |
Muscle- and synovium-derived mesenchymal-type cells differenitated into cartilage in response to a coating of partially purifed rabbit bone morphogenetic protein (BMP) on a substratum of plastic. Observed by means of phase contrast microscopy, light microscope histochemistry, and electron microscopy, the sequence of events on a BMP-coated plastic substratum is the same as that observed on a substratum of bone matrix. The plastic eliminates the possibility of any endogenous allogeneic matrix-derived BMP contaminating the system. The differntiation of cartilage from synoviocytes and subsynovial cells resembles the pathologic process occurring in human chondromatosis.
In osteoarthritis, the articular cartilage typically shows evidence of both destruction and repair. As regards the latter, differenctiation of mesenchymal cells into chondrocytes can be observed, opening up prospects of cartilage regeneration. As a biological factor capable of inducing chondrocyte differentiation, bone morpho
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genetic protein (BMP), obtained from bone matrix, has been studied in animal models of cartilage repair. BMP was prepared as a crude fraction (molecular weight about 20,000) from rabbit long bone by decalcification, extraction, dialysis and purification. Mesenchymal cells from rat fetal muscle or synovial cells from mature rabbits were exposed to BMP after 2-3 successive monolayr cultures. Both showed chondrocyte differentiation within 20 days, in contrast to control cultures (without BMP) which only produced fibroblasts. The functional competence of the new chondrocytes differentiated under the influence of BMP was shown by proteoglycan synthesis and the formation of large chondrocyie nodules, with evidence of chondrocyte assembly when diclofenac sodium or indomethacin was introduced into the BMP culture (at near-therapeutic concentrations of IxlO^6 and IxlO^5 mol/I) neither compound caused any inhibitory effect on cell adhesion, chondrocyte differentiation, or proteoglycan synthesis. Only at concentrations above the therapeutic range (10^<-1>mol/I) was proteoglycansynthesis found to be suppressed.
We investigated the activity of peptidases in the serum of mice with experimental polyarthritis that was induced by the injection of type II collagen, and experimental model of human rheumatoid arthritis. The activity of dipeptidyl peptidase II (DPP II) was increased and that of dipeptidl peptidase IV (DPP IV) was decreased resulting in the significant increase of the serum DPP II/DPP IV ratio is a novel index of disease activity in mnice with collagen-induced polyarthritis and may be useful in assessing the activity of rheumatoid arthritis in humans. Less
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