Activation of NF-kappaB is involved in the survival of osteoclasts promoted by interleukin-1.

We previously reported that interleukin-1 (IL-1) promoted the survival of murine osteoclast-like cells (OCLs) formed in vitro and activated a transcription factor, NF-kappaB, of OCLs. The present study examined whether the activation of NF-kappaB is directly involved in the survival of OCLs promoted by IL-1. The expression of IL-1 type I receptor mRNA in OCLs was detected by the polymerase chain reaction amplification of reverse-transcribed mRNA. An electrophoretic mobility shift assay showed that IL-1 transiently activated NF-kappaB in the nuclei of the OCLs, and the maximal activation occurred at 30 min. The degradation of IkappaBalpha coincided with the activation of NF-kappaB in the OCLs. The immunocytochemical study revealed that p65, a subunit of NF-kappaB, was translocated from the cytoplasm into almost all of the nuclei of the OCLs within 30 min after IL-1 stimulation. The purified OCLs spontaneously died via apoptosis, and IL-1 promoted the survival of OCLs by preventing their apoptosis. The pretreatment of purified OCLs with proteasome inhibitors suppressed the IL-1-induced activation of NF-kappaB and prevented the survival of OCLs supported by IL-1. When OCLs were pretreated with antisense oligodeoxynucleotides to p65 and p50 of NF-kappaB, the expression of respective mRNAs by OCLs was suppressed, and the IL-1-induced survival of OCLs was concomitantly inhibited. These results indicate that IL-1 promotes the survival of osteoclasts through the activation of NF-kappaB.