{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T07:45:24Z","timestamp":1792395924516,"version":"4.4.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2010,4,30]],"date-time":"2010-04-30T00:00:00Z","timestamp":1272585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Gene targeting of the p50 and p52 subunits of NF-\u03baB has shown that NF-\u03baB plays a critical role in osteoclast differentiation. However, the molecular mechanism by which NF-\u03baB 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 owing to an inactive form of NF-\u03baB-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 also was suppressed. RANKL still induced the degradation of I\u03baB\u03b1 and activated classical NF-\u03baB, 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 IKK\u03b1 or p52 restored osteoclastogenesis in aly\/aly cells. Finally, transfection of either wild-type p100, p100\u0394GRR that cannot be processed to p52, or p52 into NF-\u03baB2-deficient cells followed by RANKL treatment revealed a strong correlation between the number of osteoclasts induced by RANKL and the ratio of p52 to p100 expression. Our data provide a new finding for a previously unappreciated role for NF-\u03baB in osteoclast differentiation. \u00a9 2010 American Society for Bone and Mineral Research<\/jats:p>","DOI":"10.1359\/jbmr.091032","type":"journal-article","created":{"date-parts":[[2009,10,29]],"date-time":"2009-10-29T17:11:51Z","timestamp":1256836311000},"page":"1058-1067","source":"Crossref","is-referenced-by-count":55,"title":["Processing of the NF-\u03baB2 precursor p100 to p52 is critical for RANKL-induced osteoclast differentiation"],"prefix":"10.1093","volume":"25","author":[{"given":"Toshimasa","family":"Maruyama","sequence":"first","affiliation":[{"name":"Division of Oral Reconstruction and Rehabilitation, Department of Oral Functional Reconstruction, Kyushu Dental College, Fukuoka, Japan"},{"name":"Division of Molecular Signaling and Biochemistry, Department of Bioscience, Kyushu Dental College, Fukuoka, 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