Oxytocin is an anabolic bone hormone

Roberto Tamma, Graziana Colaianni, Ling Ling Zhu, Adriana DiBenedetto, Giovanni Greco, Gabriella Montemurro, Nicola Patano, Maurizio Strippoli, Rosaria Vergari, Lucia Mancini, Silvia Colucci, Maria Grano, Roberta Faccio, Xuan Liu, Jianhua Li, Sabah Usmani, Marilyn Bachar, Itai Bab, Katsuhiko Nishimori, Larry J. YoungChristoph Buettner, Jameel Iqbal, Li Sun, Mone Zaidi, Alberta Zallone

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

We report that oxytocin (OT), a primitive neurohypophyseal hormone, hitherto thought solely to modulate lactation and social bonding, is a direct regulator of bone mass. Deletion of OT or the OT receptor (Oxtr) in male or female mice causes osteoporosis resulting from reduced bone formation. Consistent with low bone formation, OT stimulates the differentiation of osteoblasts to a mineralizing phenotype by causing the up-regulation of BMP-2, which in turn controls Schnurri-2 and 3, Osterix, and ATF-4 expression. In contrast, OT has dual effects on the osteoclast. It stimulates osteoclast formation both directly, by activating NF-κB and MAP kinase signaling, and indirectly through the up-regulation of RANK-L On the other hand, OT inhibits bone resorption by mature osteoclasts by triggering cytosolic Ca 2+ release and NO synthesis. Together, the complementary genetic and pharmacologic approaches reveal OT as a novel anabolic regulator of bone mass, with potential implications for osteoporosis therapy.

Original languageEnglish
Pages (from-to)7149-7154
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number17
DOIs
Publication statusPublished - 2009 Apr 28

Keywords

  • Bone density
  • Osteoblast
  • Osteoclast
  • Osteoporosis
  • Pituitary hormones

ASJC Scopus subject areas

  • General

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  • Cite this

    Tamma, R., Colaianni, G., Zhu, L. L., DiBenedetto, A., Greco, G., Montemurro, G., Patano, N., Strippoli, M., Vergari, R., Mancini, L., Colucci, S., Grano, M., Faccio, R., Liu, X., Li, J., Usmani, S., Bachar, M., Bab, I., Nishimori, K., ... Zallone, A. (2009). Oxytocin is an anabolic bone hormone. Proceedings of the National Academy of Sciences of the United States of America, 106(17), 7149-7154. https://doi.org/10.1073/pnas.0901890106