Destruction and repair of articular cartilage in osteoarthritis and rheumatoid arthritis. From the point of the analysis of matrix macro-molecules

骨关节炎和类风湿关节炎中关节软骨的破坏和修复。

• 批准号: 04454374
• 负责人: IWATA Hisashi
• 金额: $ 4.16万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454374/
• 关键词: Articular cartilage destruction; Articulr cartilage repair; Effect of NSAID; BMP (Bone Morphogenetic Protein) induced cartilage; Dipeptidyl peptidase IV; Dipeptidyl peptidase II; RA, OA synovial fulid; 軟骨マトリックス欠損マウス

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 … More 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

肌肉和滑膜衍生的间充质型细胞因在塑料的底物上的部分净化的兔骨形态发生蛋白（BMP）的涂层而分化为软骨。通过相对比显微镜，光学显微镜组织化学和电子显微镜观察到，在BMP涂层塑料底物上的事件序列与在骨基质的底物上观察到的事件相同。塑料消除了任何内源性同种异体基质衍生的BMP污染系统的可能性。在骨关节炎中，滑膜和亚式小细胞的软骨的差异类似于在人软骨中发生的病理过程，关节软骨通常显示出破坏和修复的证据。关于后者，可以观察到间充质细胞向软骨细胞的差异，从而打开了软骨再生的前景。作为能够诱导软骨细胞分化的生物学因子，骨形态……更多的遗传蛋白（BMP）已从骨基质中获得，已经研究了软骨修复的动物模型。 BMP是通过脱钙化，提取，透析和纯化来制备的，是从兔子长骨中从兔子长骨中制备的。 2-3个成功的单层培养物后，将大鼠胎儿肌肉或滑膜细胞的间充质细胞暴露于BMP。两者都显示了20天内的软骨细胞分化，与仅产生成纤维细胞的对照培养物（无BMP）相比。 The functional competence of the new chondrocytes differentiated under the influence of BMP was shown by proteoglycan synthesis and the formation of large chondrocyte 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对细胞粘附，软骨细胞分化或蛋白聚糖合成的任何抑制作用。仅在蛋白聚糖的合成中，仅在高于治疗范围（10^<-1> mol/i）的浓度下被抑制。我们研究了通过注射II型胶原蛋白和人类鼻鼻炎实验模型引起的实验性多关节炎的小鼠血清中petidase的活性。 The activity of dipeptidyl peptide II (DPP II) was increased and that of dipeptidl peptide 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.较少的

项目成果

Y.Hasegawa,H.Iwata,M.Mizuno,E.Genda,S.Sato and T.Miura.: "The natural course of osteoarthritis of the hip due to subluxation or acetabular dysplasia." Arch Orthop Trauma Surg.111. 187-191 (1992)

Y.Hasekawa、H.Iwata、M.Mizuno、E.Genda、S.Sato 和 T.Miura.：“由于半脱位或髋臼发育不良导致的髋部骨关节炎的自然病程。”

H.Iwata,Y.Hasegawa,M.Mizuno,E.Genda,Y.Kataoka and A.Kada.: "Nagoya J.Med.Sci. 54" Progression of Avascular Necrosis of Femoral Head and Choice of Treatment., 27-39 (1992)

H.Iwata，Y.Hasekawa，M.Mizuno，E.Genda，Y.Kataoka 和 A.Kada.：“名古屋 J.Med.Sci. 54”股骨头缺血性坏死的进展和治疗选择。，27-

Y.Kataoka,Y.Hasegawa,H.Iwata,T.Matsuda,E.Genda,T.Miura,and H.Takahashi.: "Effect of hyperbaric oxygenation on femoral head osteonecrosis in spontaneously hypertensive rats." Acta Orthop.Scand.63. 527-530 (1992)

Y.Kataoka、Y.Hasekawa、H.Iwata、T.Matsuda、E.Genda、T.Miura 和 H.Takahashi.：“高压氧对自发性高血压大鼠股骨头坏死的影响”。

H.Iwata, S.Torii, Y.Hasegawa, H.Itoh, M.Mizuno, E.Genda, and Y.Kataoka: "Indication and Results of Vascularized Pedicle Iliac Bone Graftin Avascular Necrosis of the Femoral Head." Clin.Orthop.295. 281-288 (1993)

H.Iwata、S.Torii、Y.Hasekawa、H.Itoh、M.Mizuno、E.Genda 和 Y.Kataoka：“血管蒂髂骨移植股骨头缺血性坏死的适应症和结果”。

S.Sakano,Y.Murata,T.Miura,H.Iwata,K.Sato,N.Matsui and H.Seo.: "Collagen and Alkaline Phosphatase Gene Expression During Cartilage and Bone Differentiation by Bone Morphogenetic Protein." Clin.Orthop.292. 337-344 (1993)

S.Sakano、Y.Murata、T.Miura、H.Iwata、K.Sato、N.Matsui 和 H.Seo.：“骨形态发生蛋白在软骨和骨分化过程中胶原蛋白和碱性磷酸酶基因的表达”。