Induction of growth plate cartilage ossification by basic fibroblast growth factor.

In mammals, longitudinal bone growth results from the precise coupling of chondrogenesis and osteogenesis within the epiphyseal growth plate, a process termed endochondral ossification. The mechanisms coupling chondrogenesis and osteogenesis are unknown. Previous studies have shown that both basic fibroblast growth factor (bFGF) and acidic FGF are expressed by growth plate chondrocytes. Here we show that bFGF, infused directly into the rabbit proximal tibial growth plate, accelerates vascular invasion and ossification of growth plate cartilage. Our results suggest the possibility that bFGF (or a related member of the FGF family) couples osteogenesis to chondrogenesis by attracting vascular and bone cell invasion from the adjacent metaphyseal bone.

Catch-up growth after glucocorticoid excess: a mechanism intrinsic to the growth plate.

In humans and other mammals, the release from growth-inhibiting conditions, such as glucocorticoid excess, leads to supranormal linear growth. The prevailing explanation for this catch-up growth involves a central nervous system mechanism that compares actual body size to an age-appropriate set-point and adjusts growth rate accordingly via a circulating factor. Although such a neuroendocrine "sizostat" was hypothesized more than 30 yr ago, its existence has never been confirmed experimentally. Here we show that suppression of growth within a single growth plate by locally administered glucocorticoid is followed by local catch-up growth that is restricted to the affected growth plate. Thus, the catch-up growth cannot be explained by neuroendocrine mechanism but, rather, must arise from a mechanism intrinsic to the growth plate. To explain this finding, we propose that the normal senescent decline in growth plate function depends not on age per se, but on the cumulative number of stem cell divisions, and that glucocorticoid administration, by suppressing stem cell proliferation, delays senescence, resulting in catch-up growth after the growth-inhibiting agent is removed.