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This Article Accepted manuscript (PDF) Supplementary figures All Versions of this Article: JOE-09-0307v1 JOE-09-0307v2    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chagin, A. S Articles by Savendahl, L. PubMed PubMed Citation Articles by Chagin, A. S Articles by Savendahl, L.

A Chagin, Woman and Child Health, Karolinska Institutet, Stockholm, Sweden
E Karimian, Woman and Child Health, Karolinska Institutet, Stockholm, Sweden
K Sundström, Woman and Child Health, Karolinska Institutet, Stockholm, Sweden
E Eriksson, Woman and Child Health, Karolinska Institutet, Stockholm, Sweden
L Savendahl, Woman and Child Health, Karolinska Institutet, Stockholm, Sweden

Correspondence: Andrei S Chagin, Email: Andrei.Chagin{at}gmail.com

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. We here 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 ex vivo characterize the phenomenon of catch-up growth without any influence of systemic factors. The relevance of the model was confirmed by the demonstration that the growth of fetal and postnatal bones were stimulated by insulin-like growth factor-I (100 ng/ml) and inhibited by dexamethasone (Dexa; 1 µM). 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 up-regulation of chondrocyte proliferation.