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.