Chondrogenesis of expanded adult human articular chondrocytes is enhanced by specific prostaglandins.

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.