Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF, 1171K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Van Epps, H. L. Search for Related Content PubMed Articles by Van Epps, H. L. Related Collections Related Article Social Bookmarking                            What's this?

Deconstructing IB kinase

On page 1677, Ruocco et al. show that the formation of bone-resorbing osteoclasts is crippled when the ß subunit of the NF-B–activating IB kinase (IKK) complex is missing. The absence of IKKß also protected mice against inflammatory-induced bone loss, a complication of inflammatory diseases such as rheumatoid arthritis (RA) that is caused by excessive activation of osteoclasts.

The ß subunit of the IB kinase complex is required for inflammation-induced bone loss (arrows).

The osteoclast growth factor RANKL (receptor activator of NF-B ligand) activates the transcription factor NF-B, which promotes osteoclast development. NF-B activation requires the upstream IKK complex (IKK, ß, ), which releases NF-B from its inhibitor protein. Although a recent report showed that the IKK complex is required for osteoclast development, the relative importance of the two catalytic subunits of IKK (, ß) in this process remained unclear.

Ruocco et al. now show that mice lacking IKKß were unable to generate osteoclasts and developed severe osteopetrosis (increased bone formation), whereas those lacking IKK activity had no apparent bone abnormalities. The IKKß-deficient mice failed to transmit RANKL signals and had increased TNF-induced apoptosis in osteoclast precursors. Osteoclast formation was partially restored in mice that lacked both IKKß and the type I TNF receptor.

IKKß-deficient mice were also resistant to inflammatory bone loss and this resistance was dependent on TNF-derived signals. Thus the authors suggest that drugs designed to block IKKß may prevent bone loss in patients. However, they caution that such drugs, if developed, should perhaps not be combined with anti-TNF therapy (commonly used to treat RA) as the combination may not be effective.

hvanepps{at}rockefeller.edu

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

IB kinase (IKK)ß, but not IKK, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss

Maria Grazia Ruocco, Shin Maeda, Jin Mo Park, Toby Lawrence, Li-Chung Hsu, Yixue Cao, Georg Schett, Erwin F. Wagner, and Michael Karin
J. Exp. Med. 2005 201: 1677-1687. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 1171K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Van Epps, H. L. Search for Related Content PubMed Articles by Van Epps, H. L. Related Collections Related Article Social Bookmarking                            What's this?