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Mol Cell Endocrinol. 1996 Oct 14;123(1):27-35.

Prostaglandin E2 stimulates incorporation of proline into collagenase digestible proteins in human articular chondrocytes: identification of an effector autocrine loop involving insulin-like growth factor I.

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Department of Medicine, University of Montreal, Quebec, Canada.


Prostaglandin E2 (PGE2) stimulates collagen gene promoter activity in transfected human chondrocytes though no canonical cyclic AMP (cAMP) response element has been yet identified. Human insulin-like growth factor-1 (IGF-1) induces an increase in collagen type II expression and synthesis in chondrocytes. Since our preliminary data suggested that PGE2 can stimulate IGF-1 release from human articular chondrocytes, we examined whether the eicosanoid could influence collagen synthesis and whether the effect was mediated by IGF-1. Incubation of primary cultures of human articular chondrocytes with increasing concentrations of PGE2 resulted in a dose-dependent (ANOVA, F= 51.62, P < 0.0001, n = 5) and saturable increase in the synthesis and release of IGF-1 and expression of IGF-1 mRNA. At relatively low concentrations (30 pmol/1 to 30 nmol/l), PGE2 stimulated an increase in the incorporation of [3H]proline into collagenase digestible protein (CDP) (P < 0.01, n = 5) whereas at high levels (300 nmol/l to 3 micromol/l) of the eicosanoid, incorporation diminished precipitously. Human IGF-1 mimicked the effects of low PGE2 concentrations by stimulating in a dose-dependent (ANOVA, F= 31.65, P < 0.001, n = 3) and saturable fashion the incorporation of [3H]proline into CDP although the magnitude of the response induced by IGF-1 was far greater (3.5-fold). An IGF-1 receptor blocking antibody completely abrogated the IGF-1 induced response suggesting that the effect was specifically IGF-1 receptor mediated. Furthermore, the PGE2-induced increase in [3H]proline incorporation into CDP was inhibited (63%, P < 0.001, n = 7) by the addition to the culture medium of an anti-IGF-1 antibody. We conclude that PGE2 may act as a secretagogue of IGF-1 and that the latter growth factor may mediate, via an autocrine loop and the IGF-1 receptor, at least some of the anabolic effects of the eicosanoid on cartilage metabolism.

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