183, 237, 249, 252 TRAPPC9 knockdown study using siRNA showed deficiency in nerve growth factor-induced neuronal differentiation of PC12 cells through the attenuation of the TNFα-induced NF-κB activation and decreases the expression Bcl-xL gene.167 These studies underline the involvement of TRAPPC9 in NF-κB pathway activation during nervous system …show more content…
NF-κB activation is known to be controlled through the canonical or classical 187 and non-canonical or alternate pathway333. The canonical activation is mediated through the translocation of the 65-kDa RelA and the 50-kDa NF-κB1 DNA-binding subunit, whereas, the non-canonical is thought to be mediated through the processing and translocation of the RelB complex. Emerging evidence shows that NF-κB activation negatively regulates osteoblast differentiation and function.7, 59 Inflammatory cytokines, in particular TNFα, provided the first indication of the inhibitor effect of the classical NF-κB pathway on bone formation in vivo and in vitro.129 The inhibitory effect of TNFα on osteoblast differentiation was mediated through Runx2 inhibition and was NF-kB dependent220. TNFα- and TNFR1- deficient mice showed increased basal bone mass in vivo and increased OB differentiation in vitro.220 Neil et al.7 showed that inhibition of NF-κB using S1627 NF-κB inhibitor increased osteoblast differentiation and bone formation through the up-regulation of osteoblast specific genes in vivo followed by an increased bone formation and repair bone defect in mouse calvarias critical defect model. The role on the non-classical NF-κB pathway in osteoblast was investigated by Chang et al.167 who showed that time and stage –specific inhibition of the IKK/NF-κB significantly increased