Catch-up growth after dexamethasone withdrawal occurs in cultured postnatal rat metatarsal bones.
Children exposed to systemic glucocorticoids often exhibit growth retardation and after the cessation of therapy catch-up growth occurs in many, but not all patients. The developmental regulation and underlying cellular mechanisms of catch-up growth are not fully understood. To clarify this issue, we established an in vitro model of catch-up growth. Here we present a protocol for the long-term culture (up to 160 days) of fetal (E20) as well as postnatal (P8) rat metatarsal bones which allowed us to characterize ex vivo the phenomenon of catch-up growth without any influence by systemic factors. The relevance of the model was confirmed by the demonstration that the growth of fetal and postnatal bones were stimulated by IGF1 (100 ng/ml) and inhibited by dexamethasone (Dexa; 1 microM). We found that the capacity to undergo catch-up growth was restricted to postnatal bones. Catch-up growth occurred after postnatal bones had been exposed to Dexa for 7 or 12 days but not after a more prolonged exposure (19 days). Incomplete catch-up growth resulted in compromised bone length when assessed at the end of the 4-month period of culture. While exposure to Dexa was associated with decreased chondrocyte proliferation and differentiation, catch-up growth was only associated with increased cell proliferation. We conclude that the phenomenon of catch-up growth after Dexa treatment is intrinsic to the growth plate and primarily mediated by an upregulation of chondrocyte proliferation.
Chagin
Andrei S
AS
Pediatric Endocrinology Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Stockholm SE-17176, Sweden. achagin@partners.org
Karimian
Elham
E
Sundström
Katja
K
Eriksson
Emma
E
Sävendahl
Lars
L
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D047109:Fetal Development / Q000187:drug effects*; D005333:Fetus; D005938:Glucocorticoids / Q000008:administration & dosage*; D006128:Growth / Q000187:drug effects; D006132:Growth Plate / Q000187:drug effects / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008682:Metatarsal Bones / Q000196:embryology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D046509:Tissue Culture Techniques
D005938:Glucocorticoids; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone