Chondrogenesis of expanded adult human articular chondrocytes is enhanced by specific prostaglandins
Chondrogenesis of expanded adult human articular chondrocytes is enhanced by specific prostaglandins
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DOI：
10.1093/rheumatology/keh197
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发表时间：
2004-07-01
期刊：
影响因子：
5.5
通讯作者：
Martin, I
中科院分区：
文献类型：
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作者：
Jakob, M;Démarteau, O;Martin, I
Objective.研究环氧化酶-2（考克斯-2）依赖的前列腺素D-2（PGD（2））、E-2（PGE（2））和F（2）α（PGF（2）α）对去分化关节软骨细胞再分化和软骨基质生成的影响。通过单层扩增使来自三个成年供体的人关节软骨细胞去分化，并通过在含有TGF-β（1）和地塞米松的确定的无血清培养基中培养成3D团块诱导再分化，所述培养基不含或进一步补充PGD（2）、PGE（2）或PGF（2）α。2周后，通过组织学、免疫化学、生物化学和实时定量逆转录聚合酶链反应对颗粒进行评估。所有三种PG，但主要是PGE（2），降低了I型胶原颗粒的染色强度，而PGD（2）和PGF（2）α增加了II型胶原和糖胺聚糖（GAG）颗粒的染色强度。颗粒的GAG/DNA含量不受PGE（2）的影响，但PGD（2）和PGF（2）α分别使其增加1.5倍和2.1倍。PGE（2）降低I型胶原mRNA的表达（9.0倍），而PGD（2）和PGF（2）α分别增加II型胶原和聚集蛋白聚糖mRNA的表达（分别为6.2和4.1倍和29.8和10.7倍）。与PGE（2）相反，PGD（2）和PGF（2）α通过扩增的人关节软骨细胞增强软骨形成分化和透明软骨基质沉积，因此可以用于改善基于这些细胞的体外或体内软骨再生方法。
Objective. To investigate the effects of the cyclooxygenase-2 (cox-2)-dependent prostaglandins D-2 (PGD(2)), E-2 (PGE(2)) and F(2)alpha (PGF(2)alpha) on the redifferentiation and cartilage matrix production of dedifferentiated articular chondrocytes.Methods. Human articular chondrocytes from three adult donors were dedifferentiated by monolayer expansion and induced to redifferentiate by culture as 3D pellets in a defined serum-free medium containing TGF-beta(1) and dexamethasone, without or with further supplementation with PGD(2), PGE(2) or PGF(2)alpha. After 2 weeks, pellets were assessed histologically, immunohistochemically, biochemically and by real-time quantitative reverse transcriptase-polymerase chain reaction.Results. All three PGs, but predominantly PGE(2), reduced the staining intensity of pellets for collagen type I, whereas PGD(2) and PGF(2)alpha increased the staining intensity of pellets for collagen type II and glycosaminoglycans (GAG). The GAG/DNA content of pellets was not affected by PGE(2) but was increased 1.5- and 2.1-fold by PGD(2) and PGF(2)alpha respectively. PGE(2) reduced the expression of collagen type I mRNA (9.0-fold), whereas PGD(2) and PGF(2)alpha increased the mRNA expression of collagen type II (6.2- and 4.1-fold respectively) and aggrecan (29.8- and 10.7-fold respectively).Conclusion. In contrast to PGE(2), PGD(2) and PGF(2)alpha enhanced chondrogenic differentiation and hyaline cartilage matrix deposition by expanded human articular chondrocytes, and could thus be used to improve in vitro or in vivo cartilage regeneration approaches based on these cells.