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

肌肉和滑膜来源的间充质型细胞分化成软骨，以响应部分纯化的兔骨形态发生蛋白（BMP）的塑料基质上的涂层。通过相差显微镜、光学显微镜组织化学和电子显微镜观察，BMP涂层塑料基质上的事件顺序与骨基质上观察到的事件顺序相同。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。软骨从滑膜细胞和滑膜下细胞的分化类似于人类软骨瘤病的病理过程。在骨关节炎中，关节软骨典型地表现出破坏和修复的迹象。对于后者，可以观察到间充质细胞分化为软骨细胞，开辟了软骨再生的前景。骨形态作为一种能够诱导软骨细胞分化的生物因子， ...更多信息 已在软骨修复的动物模型中研究了从骨基质中获得的遗传蛋白（BMP）。从兔长骨中通过脱钙、提取、透析和纯化制备BMP作为粗级分（分子量约20，000）。在连续单层培养2-3次后，将来自大鼠胎儿肌肉的间充质细胞或来自成熟兔的滑膜细胞暴露于BMP。两者均在20天内显示出软骨细胞分化，与仅产生成纤维细胞的对照培养物（无BMP）形成对比。BMP作用下分化的新软骨细胞的功能能力表现为蛋白多糖的合成和大软骨细胞结节的形成，当双氯芬酸钠或吲哚美辛引入BMP培养物时，软骨细胞组装的证据（在接近治疗浓度的1 × 10^6和1 × 10^5 mol/l下）两种化合物均未对细胞粘附、软骨细胞分化或蛋白聚糖合成。只有在浓度高于治疗范围（10 μ <-1>mol/l）时，蛋白聚糖合成才被抑制。我们研究了注射II型胶原诱导的实验性多关节炎小鼠和人类类风湿性关节炎实验模型血清中肽酶的活性。二肽基肽酶II（DPP II）活性增加，二肽基肽酶IV（DPP IV）活性降低，导致血清DPP II/DPP IV比值显著增加，这是一种新的胶原诱导的多发性关节炎小鼠疾病活动性指标，可用于评估人类类风湿性关节炎的活动性。少

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。”

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,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-

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”。

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”。