Insulin exerts direct, IGF-1 independent actions in growth plate chondrocytes
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AbstractInsufficient insulin production or action in diabetic states is associated with growth retardation and impaired bone healing, while the underling mechanisms are unknown. In this study, we sought to define the role of insulin signaling in the growth plate. Insulin treatment of embryonic metatarsal bones from wild-type mice increased chondrocyte proliferation. Mice lacking insulin receptor (IR) selectively in chondrocytes (CartIR(-/-)) had no discernable differences in total femoral length compared to control littermates. However, CartIR(-/-) mice exhibited an increase in chondrocyte numbers in the growth plate than that of the controls. Chondrocytes lacking IR had elevated insulin-like growth factor (IGF)-1R mRNA and protein levels. Subsequently, IGF-1 induced phosphorylation of Akt and ERK was enhanced, while this action was eliminated when the cells were treated with IGF-1R inhibitor Picropodophyllin. Deletion of the IR impaired chondrogenic differentiation, and the effect could not be restored by treatment of insulin, but partially rescued by IGF-1 treatment. Intriguingly, the size of hypertrophic chondrocytes was smaller in CartIR(-/-) mice when compared with that of the control littermates, which was associated with upregulation of tuberous sclerosis complex 2 (TSC2). These results suggest that deletion of the IR in chondrocytes sensitizes IGF-1R signaling and action, IR and IGF-1R coordinate to regulate the proliferation, differentiation and hypertrophy of growth plate chondrocytes.
All Author(s) ListZhang FJ, He QL, Tsang WP, Garvey WT, Chan WY, Wan C
Journal nameBone Research
Volume Number2
PublisherNature Publishing Group: Open Access Journals - Option B / Nature Publishing Group
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesCell & Tissue Engineering; Cell Biology

Last updated on 2021-02-03 at 00:33