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.