COMPARISON OF THE EFFECTS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDS) ON PROTEOGLYCAN SYNTHESIS BY ARTICULAR-CARTILAGE EXPLANT AND CHONDROCYTE MONOLAYER-CULTURES
COMPARISON OF THE EFFECTS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDS) ON PROTEOGLYCAN SYNTHESIS BY ARTICULAR-CARTILAGE EXPLANT AND CHONDROCYTE MONOLAYER-CULTURES
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DOI：
10.1016/0006-2952(91)90111-h
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发表时间：
1991-05-01
影响因子：
5.8
通讯作者：
GHOSH, P
中科院分区：
文献类型：
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作者：
COLLIER, S;GHOSH, P
实验研究了兔关节软骨细胞在非甾体抗炎药和(SO4)- s -35- o2 -存在下培养8天的蛋白多糖生物合成。采用关节软骨外植体和融合软骨细胞单层培养模型。每隔2天换一次培养基，分别检测培养期间培养基中积累的[SO-35(4)]蛋白聚糖和细胞外基质。在长期实验中，在第8天去除药物，并在10-12天的培养间隔内测定蛋白多糖的产量。所研究的药物为双氯芬酸、吲哚美辛、酮洛芬、吡罗西康和硫丙酸，浓度分别为0、0.1、1、10、50和100 μ g/mL。细胞培养产生的蛋白多糖在培养初期达到最大值，随着时间的推移，外植体产生的蛋白多糖更多。所有药物的最高浓度，特别是双氯芬酸和吲哚美辛，抑制细胞和外植体培养的蛋白多糖分泌。然而，从培养物中去除药物后，抑制蛋白多糖的产生逆转到与细胞培养物相当或高于对照组的水平，但在外植体培养物中大部分持续存在。外植体产生的蛋白多糖约有70-80%保留在基质中，而细胞培养产生的蛋白多糖约有80-90%分泌到培养基中。当药物抑制蛋白多糖的产生时，在细胞外基质和培养基中，蛋白多糖的水平降低的比例大致相同。在所检测的非甾体抗炎药中，只有酮洛芬在生理浓度（0.1 μ g/mL）下对外植体培养的PG合成有刺激作用。
Experiments were conducted to study proteoglycan biosynthesis by rabbit articular chondrocytes cultured in the presence of NSAIDs and (SO4)-S-35-O2- for up to 8 day. Both articular cartilage explants and confluent chondrocyte monolayer culture models were used. Medium was changed every 2 days and the [SO-35(4)]proteoglycans which had accumulated in the medium and the extracellular matrix during the culture intervals were assayed separately. In long-term experiments, drugs were removed on day 8, and proteoglycan production during a 10-12 day culture interval also was assayed. The drugs studied were diclofenac, indomethacin, ketoprofen, piroxicam and tiaprofenic acid, at concentrations of 0, 0.1, 1, 10, 50 and 100-mu-g/mL. Whereas proteoglycan production by cell cultures was maximal early in the culture period, explants produced more proteoglycans as time progressed. The highest concentrations of all of the drugs, especially diclofenac and indomethacin, inhibited proteoglycan secretion by both cell and explant cultures. However, after removal of the drugs from the cultures, suppressed proteoglycan production reversed to levels equivalent to, or higher than controls in the cell cultures, but largely persisted in explant cultures. About 70-80% of proteoglycans produced by explants were retained in the matrix, whereas about 80-90% of proteoglycans produced by cell cultures were secreted into the medium. Where drugs inhibited proteoglycan production, the levels were reduced by approximately the same proportions in both extracellular matrix and culture medium fractions. Of the NSAIDs examined only ketoprofen demonstrated a stimulatory effect on PG synthesis in explant cultures at a physiological concentration (0.1-mu-g/mL).