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Stimulatory Effects of Insulin-like Growth Factor-I on Growth Plate Chondrogenesis Are Mediated by Nuclear Factor-κB p65
Journal article   Open access   Peer reviewed

Stimulatory Effects of Insulin-like Growth Factor-I on Growth Plate Chondrogenesis Are Mediated by Nuclear Factor-κB p65

Shufang Wu, Doris Fadoju, Geoffrey Rezvani and Francesco De Luca
The Journal of biological chemistry, v 283(49), pp 34037-34044
05 Dec 2008
PMID: 18922796
url
https://doi.org/10.1074/jbc.m803754200View
Published, Version of Record (VoR)CC BY V4.0 Open
url
https://doi.org/10.1074/jbc.M803754200View
Published, Version of Record (VoR) Open

Abstract

Molecular Basis of Cell and Developmental Biology
Insulin-like growth factor-I (IGF-I) is an important regulator of endochondral ossification. However, little is known about the signaling pathways activated by IGF-I in growth plate chondrocytes. We have previously shown that NF-κB-p65 facilitates growth plate chondrogenesis. In this study, we first cultured rat metatarsal bones with IGF-I and/or pyrrolidine dithiocarbamate (PDTC), a known NF-κB inhibitor. The IGF-I-mediated stimulation of metatarsal growth and growth plate chondrogenesis was neutralized by PDTC. In rat growth plate chondrocytes, IGF-I induced NF-κB-p65 nuclear translocation. The inhibition of NF-κB-p65 expression and activity (by p65 short interfering RNA and PDTC, respectively) in chondrocytes reversed the IGF-I-mediated induction of cell proliferation and differentiation and the IGF-I-mediated prevention of cell apoptosis. Moreover, the inhibition of the phosphatidylinositol 3-kinase and Akt abolished the effects of IGF-I on NF-κB activation. In conclusion, our findings indicate that IGF-I stimulates growth plate chondrogenesis by activating NF-κB-p65 in chondrocytes.

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Web of Science research areas
Biochemistry & Molecular Biology
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