TRANSFORMING GROWTH FACTOR-BETA-1 STIMULATES SYNTHESIS OF PROTEOGLYCAN AGGREGATES IN CALF ARTICULAR-CARTILAGE ORGAN-CULTURES

TRANSFORMING GROWTH FACTOR-BETA-1 STIMULATES SYNTHESIS OF PROTEOGLYCAN AGGREGATES IN CALF ARTICULAR-CARTILAGE ORGAN-CULTURES
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DOI:
10.1016/0003-9861(91)90013-9
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发表时间:
1991-04-01
影响因子:
3.9
通讯作者:
MORALES, TI
MORALES, TI
中科院分区:
生物学3区
文献类型:
--
作者:
MORALES, TI

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以前的工作表明,转化生长因子-β1(TGF-β1),单独添加到牛软骨器官培养,刺激[35 S]硫酸盐掺入到大分子材料,但没有调查的保真度刺激系统,以维持软骨型蛋白聚糖的合成。本文提供了软骨细胞在TGF-β1刺激下合成适当蛋白多糖基质的证据:(i)透明质酸和蛋白多糖单体合成协调增加,(ii)组装连接稳定的蛋白多糖聚集体,(iii)合成混合硫酸软骨素/硫酸角质素单体物质,(iv)蛋白质核心合成增加。当将在TGF-β1刺激下合成的蛋白聚糖与在基础条件下合成的蛋白聚糖进行比较时,观察到糖基化模式的一些变化。因此,分别将TGF-β1与基础样品进行比较,单体较大(Kavon Sepharose CL-2B = 0.29 vs 0.41),硫酸软骨素链较长约3.5 kDa,硫酸角质素中总糖胺聚糖的百分比略有增加,从约4%(基础)增加到约6%,未硫酸化的二糖从28%(基础)减少到12%。所有这些变化都是在更阴离子蛋白聚糖的方向上。由于蛋白聚糖赋予软骨基质弹性的能力与其阴离子性质直接相关,因此这些变化可能对组织功能具有有益影响。
Previous work showed that transforming growth factor-β1 (TGF-β1), added alone to bovine cartilage organ cultures, stimulated [35S]sulfate incorporation into macromolecular material but did not investigate the fidelity of the stimulated system to maintain synthesis of cartilage-type proteoglycans. This paper provides evidence that chondrocytes synthesize the appropriate proteoglycan matrix under TGF-β1 stimulation: (i) there is a coordinated increase in hyaluronic acid and proteoglycan monomer synthesis, (ii) link-stable proteoglycan aggregates are assembled, (iii) the hybrid chondroitin sulfate/ keratan sulfate monomeric species is synthesized, and (iv) there is an increase in protein core synthesis. Some variation in glycosylation patterns was observed when proteoglycans synthesized under TGF-β1 stimulation were compared to those synthesized under basal conditions. Thus comparing TGF-β1 to basal samples respectively, the monomers were larger (Kavon Sepharose CL-2B = 0.29 vs 0.41), the chondroitin sulfate chains were longer by ~3.5 kDa, the percentage of total glycosaminoglycan in keratan sulfate increased slightly from ~4% (basal) to ~6%, and the unsulfated disaccharide decreased from 28% (basal) to 12%. All of these variations are in the direction of a more anionic proteoglycan. Since the ability of proteoglycans to confer resiliency to the cartilage matrix is directly related to their anionic nature, these changes would presumably have a beneficial effect on tissue function.