Regulation of cell proliferation in rat mandibular condylar cartilage in explant culture by insulin-like growth factor-1 and fibroblast growth factor-2.

Insulin-like growth factor-1 (IGF-1) and fibroblast growth factor-2 (FGF-2) regulate the proliferation and differentiation of growth-plate chondrocytes, but surprisingly little is known of the mechanisms underlying growth regulation in secondary cartilages such as the mandibular condylar. The aims here were to investigate whether IGF-1 and FGF-2 receptors are present in mandibular condylar cartilage in vivo from 28-day-old male Sprague-Dawley rats (by immunohistochemistry), how proliferation in that cartilage responds to increasing concentrations of exogenous IGF-1 or FGF-2 in explant culture (by [3H]thymidine incorporation), and whether the expression of these growth factors and their receptors in the cartilage changes during the transition to puberty (quantitative reverse transcriptase-polymerase chain reaction). Immunoreactivity for receptors (R) for IGF-1 and FGF-2 (IGF-1R, FGFR1, and FGFR3) was most pronounced in chondroblasts and hypertrophic chondrocytes, while FGFR2 immunoreactivity was strongest in the articular and prechondroblastic zones. The proliferative response elicited by exogenous IGF-1 was considerably greater than that induced by FGF-2, although the threshold concentration for a significant response was lower for FGF-2. In the transition from prepuberty (31 days) to the beginning of late puberty (42 days), a pronounced trend of increasing IGF-1 and decreasing FGF-2 gene expression was evident. Of the receptors, only FGFR2 and FGFR3 expression increased. These data provide evidence that proliferation in the mandibular condylar cartilage might be regulated in part by IGF-1 and FGF-2, and that expression of these genes changes considerably at puberty. The data also suggest that mechanisms governing proliferation in mandibular condylar cartilage might have as much in common with those regulating cranial sutures as those regulating growth-plate.