Activation of NF-kappaB in human osteoblasts by stimulators of bone resorption

Several bone resorptive stimuli affect osteoclasts indirectly by modulating the production and release of osteoblastic factors. Using electrophoretic mobility shift assays, we found that not only tumour necrosis factor-alpha (TNF-alpha) but also interleukin-1beta and parathyroid hormone (PTH) caused dose and time-related increases in nuclear factor kappaB (NF-kappaB)-DNA binding in Saos-2 human osteoblastic (hOB) cells. Activation of NF-kappaB by TNF-alpha was reproduced in primary hOBs. In contrast, consistent with their previously reported lack of response to steroid hormones, Saos-2 cells did not respond to 1,25-dihydroxyvitamin D(3). We suggest that NF-kappaB activation in osteoblastic cells constitutes an important pathway in osteoblast-mediated resorptive signalling.