Processing of the NF-kappaB2 Precursor, p100, to p52 is Critical for RANKL-Induced Osteoclast Differentiation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] Journal article | | Title | Processing of the NF-kappaB2 Precursor, p100, to p52 is Critical for RANKL-Induced Osteoclast Differentiation. | | Author(s) | Maruyama T, Fukushima H, Nakao K, Shin M, Yasuda H, Weih F, Doi T, Aoki K, Alles N, Ohya K, Hosokawa R, Jimi E | | Source | J Bone Miner Res 2009 Oct 29. | | Abstract | Abstract Gene targeting of p50 and p52 subunits of NF-kappaB has shown that NF-kappaB plays a critical role in osteoclast differentiation. However, the molecular mechanism by which NF-kappaB regulates osteoclast differentiation is still unclear. To address this issue, we analyzed alymphoplasia (aly/aly) mice in which the processing of p100 to p52 does not occur due to an inactive form of NF-kappaB-inducing kinase (NIK). Aly/aly mice showed a mild osteopetrosis, with significantly reduced osteoclast numbers. RANKL-induced osteoclastogenesis from bone marrow cells of aly/aly mice was also suppressed. RANKL still induced the degradation of IkappaBalpha and activated classical NF-kappaB, whereas processing of p100 to p52 was abolished by the aly/aly mutation. Moreover, RANKL-induced expression of NFATc1 was impaired in aly/aly bone marrow. Overexpression of constitutively active IKKalpha or p52 restored osteoclastogenesis in aly/aly cells. Finally, transfection of either wild-type p100, p100DeltaGRR that cannot be processed to p52, or p52 into NF-kappaB2-deficient cells followed by RANKL treatment revealed a strong correlation between the number of osteoclasts induced by RANKL and the ratio of p52 versus p100 expression. Our data provide a new finding for a previously unappreciated role for NF-kappaB in osteoclast differentiation. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19874202 |
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