{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T19:31:01Z","timestamp":1770838261815,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,10,14]],"date-time":"2009-10-14T00:00:00Z","timestamp":1255478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2009,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The transcription factor NF\u2010\u03baB is essential for osteoclastogenesis and is considered an immune\u2010modulator of rheumatoid arthritis and inflammatory osteolysis. Activation of NF\u2010\u03baB subunits is regulated by the upstream I\u03baB kinase (IKK) complex which contains IKK\u03b1, IKK\u03b2, and IKK\u03b3; the latter also known as NF\u2010\u03baB essential modulator (NEMO). The role of IKK\u03b1 and IKK\u03b2 in the skeletal development and inflammatory osteolysis has been described, whereas little is known regarding the role of NEMO in this setting. Typically, signals induced by RANK ligand (RANKL) or TNF prompt oligomerization of NEMO monomers through the coiled\u2010coil\u20102 (CC2) and leucine zipper (LZ) motifs. This step facilitates binding to IKKs and further relaying signal transduction. Given the central role of NF\u2010\u03baB in osteoclastogenesis, we asked whether NEMO is essential for osteoclastogenesis and whether interruption of NEMO oligomerization impedes osteoclast differentiation in vitro and in vivo. Using cell\u2010permeable short peptides overlapping the CC2 and LZ motifs we show that these peptides specifically bind to NEMO monomers, prevent trimer formation, and render NEMO monomers susceptible for ubiquitin\u2010mediated degradation. Further, CC2 and LZ peptides attenuate RANKL\u2010 and TNF\u2010induced NF\u2010\u03baB signaling in bone marrow\u2010derived osteoclast precursors (OCPs). More importantly, these peptides potently inhibit osteoclastogenesis, in vitro, and arrest RANKL\u2010induced osteolysis, in mice. To further ascertain its role in osteoclastogenesis, we were able to block osteoclastogenesis using NEMO siRNA knockdown approach. Collectively, our data establish that obstruction of NEMO oligomerization destabilizes NEMO monomers, inhibits NF\u2010\u03baB activation, impedes osteoclastogenesis and arrests inflammatory osteolysis. Thus, NEMO presents itself as a promising target for anti\u2010osteolytic intervention. J. Cell. Biochem. 108: 1337\u20131345, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.22364","type":"journal-article","created":{"date-parts":[[2009,10,14]],"date-time":"2009-10-14T16:17:52Z","timestamp":1255537072000},"page":"1337-1345","source":"Crossref","is-referenced-by-count":17,"title":["Impediment of NEMO oligomerization inhibits osteoclastogenesis and 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