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

将部分纯化的兔骨形态发生蛋白（BMP）包覆在塑料基质上后，肌肉和滑膜来源的间充质细胞分化为软骨。通过相衬显微镜、光镜组织化学和电子显微镜观察，bmp涂层塑料基质上的事件序列与骨基质基质上的事件序列相同。这种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，关节软骨典型地显示出破坏和修复的证据。后者可以观察到间充质细胞向软骨细胞的分化，为软骨再生开辟了前景。骨形态蛋白（bone morpho…More genetic protein， BMP）作为一种能够诱导软骨细胞分化的生物因子，已在软骨修复动物模型中进行了研究。以兔长骨为原料，经脱钙、提取、透析、纯化等工艺制备BMP粗馏分（分子量约20000）。将大鼠胎肌间充质细胞或成熟兔滑膜细胞连续培养2-3次后暴露于BMP中。两者在20天内均显示软骨细胞分化，而对照培养（不含BMP）只产生成纤维细胞。在BMP影响下分化的新软骨细胞的功能能力通过蛋白聚糖合成和大软骨细胞结节的形成来证明，当双氯芬酸钠或吲哚美辛入BMP培养物（接近治疗浓度的IxlO^6和IxlO^5 mol/I）时，软骨细胞组装的证据，这两种化合物对细胞粘附、软骨细胞分化或蛋白聚糖合成都没有任何抑制作用。只有在浓度高于治疗范围（10^<-1>mol/I）时，才发现蛋白多糖合成受到抑制。我们研究了II型胶原诱导的实验性多发性关节炎小鼠和类风湿关节炎实验模型血清中肽酶的活性。二肽基肽酶II （DPP II）活性升高，二肽基肽酶IV （DPP IV）活性降低，导致血清DPP II/DPP IV比值显著升高，是胶原诱导的多发性关节炎患者疾病活动性的新指标，可用于评估人类类风湿关节炎的活动性。少

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