{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:17:51Z","timestamp":1792552671766,"version":"4.5.0"},"reference-count":22,"publisher":"National Academy of Sciences","issue":"43","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,10,25]]},"abstract":"<jats:p>The sympathetic nervous system suppresses bone mass by mechanisms that remain incompletely elucidated. Using cell-based and murine genetics approaches, we show that this activity of the sympathetic nervous system requires osteopontin (OPN), a cytokine and one of the major members of the noncollagenous extracellular matrix proteins of bone. In this work, we found that the stimulation of the sympathetic tone by isoproterenol increased the level of OPN expression in the plasma and bone and that mice lacking OPN (OPN-KO) suppressed the isoproterenol-induced bone loss by preventing reduced osteoblastic and enhanced osteoclastic activities. In addition, we found that OPN is necessary for changes in the expression of genes related to bone resorption and bone formation that are induced by activation of the sympathetic tone. At the cellular level, we showed that intracellular OPN modulated the capacity of the \u03b22-adrenergic receptor to generate cAMP with a corresponding modulation of cAMP-response element binding (CREB) phosphorylation and associated transcriptional events inside the cell. Our results indicate that OPN plays a critical role in sympathetic tone regulation of bone mass and that this OPN regulation is taking place through modulation of the \u03b22-adrenergic receptor\/cAMP signaling system.<\/jats:p>","DOI":"10.1073\/pnas.1109402108","type":"journal-article","created":{"date-parts":[[2011,10,11]],"date-time":"2011-10-11T23:37:30Z","timestamp":1318376250000},"page":"17767-17772","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":80,"title":["Sympathetic control of bone mass regulated by osteopontin"],"prefix":"10.1073","volume":"108","author":[{"given":"Masashi","family":"Nagao","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology, Medical Research Institute, and"},{"name":"Global Center of Excellence Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8510 Tokyo, Japan;"},{"name":"Department of Orthopedics, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, 113-8421 Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy N.","family":"Feinstein","sequence":"additional","affiliation":[{"name":"Laboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Ezura","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Medical Research Institute, and"},{"name":"Global Center of Excellence Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8510 Tokyo, Japan;"},{"name":"Advanced Bone and Joint Science Program, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8510 Tokyo, 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