Ontogenesis of IGF regulation of longitudinal bone growth in rat metatarsal rudiments cultured in serum-free medium.

The aim of this study was to compare the effect of two cytokines, IGF-I and IGF-II on skeletal development in the rat. The three medial metatarsal rudiments were dissected out from fetuses at days 19, 20 or 21 of gestation and from newborns at days 1, 3, 6 and 9 after birth, then grown in serum-free MEM medium at 37 degrees C and 5% CO2 in air. From day 19 of gestation to the end of experiment, longitudinal bone growth (mm) was significantly increased by IGF-I (2.975 +/- 0.050) and IGF-II (2.530 +/- 0.062), compared to controls (2.188 +/- 0.060). In the same way, the width (mm) at the last experimental day was 0.360 +/- 0.010 in IGF-I- and 0.327 +/- 0.008 in IGF-II-treated bones, respectively (vs 0.313 +/- 0.012 in controls). Mineralization was also stimulated under both growth factors (length of the calcified diaphysis (mm): 0.691 +/- 0.019 in IGF-I- and 0.446 +/- 0.017 in IGF-II-treated bones; vs 0.383 +/- 0.024 in controls). IGF-I and IGF-II (but to a lesser extent) stimulation was due to an increased DNA synthesis (3H-thymidine uptake) as well as protein anabolism (incorporated proline). In addition, cartilage activity (35S captation) and mineralization (45Ca fixed) were involved in the action of these cytokines. An age dependency of bone response to IGFs was pointed out, the effect being higher during the fetal period than after birth. In conclusion, our results raise the possibility that IGF-II, as well as IGF-I, is involved in the control of osteogenesis.