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United States Department of Agriculture

Agricultural Research Service

Research Project: BONE METABOLISM IN OBESITY Title: Bone marrow oxytocin mediates the anabolic action of estrogen on the skeleton

item Colaianni, Graziana -
item Sun, Li -
item Di Benedetto, Andriana -
item Tamma, Roberto -
item Zhu, Ling-Ling -
item Cao, Jay
item Grano, Maria -
item Yuan, Tony -
item Colucci, Sylva -
item Cuscito, Concetta -
item Mancini, Lucia -
item Li, Jinhua -
item Nishimori, Katsuhiko -
item Bab, Itai -
item Lee, Heon-Jin -
item Iqbal, Jameel -
item Young, W. Scott -
item Rosen, Clifford -
item Zallone, Alberta -
item Zaidi, Mone -

Submitted to: Proceedings of the National Academy of Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 18, 2012
Publication Date: August 17, 2012
Repository URL:
Citation: Colaianni, G., Sun, L., Di Benedetto, A., Tamma, R., Zhu, L., Cao, J.J., Grano, M., Yuan, T., Colucci, S., Cuscito, C., Mancini, L., Li, J., Nishimori, K., Bab, I., Lee, H., Iqbal, J., Young, W., Rosen, C., Zallone, A., Zaidi, M. 2012. Bone marrow oxytocin mediates the anabolic action of estrogen on the skeleton. Proceedings of the National Academy of Sciences. 287(34):29159-29167.

Interpretive Summary: Oxytocin (OT) is a nanopeptide synthesized in the hypothalamus and released into circulation by the posterior pituitary. Its primary function is to mediate the milk ejection reflex in nursing mammals1. It also augments uterine contraction during parturition2. Serum OT levels peak during late pregnancy and lactation. These periods correspond, respectively, to maximal fetal and post-natal bone growth, because of which, the mother must loose ~120g of calcium from her skeleton3,4. Hormonal adaptations, including low estrogen and elevated PTHrP levels, permit this maternal hyper-resorption and intergenerational calcium transfer5. However, it is surprising that shortly after these periods of profound bone loss, the mother’s skeleton is rapidly repleted; if not, pregnancy- and lactation-associated osteoporosis ensues. The mechanisms for this dramatic skeletal recovery remain poorly understood.

Technical Abstract: Estrogen withdrawal in women due to natural or artificial menopause is followed by rapid bone loss, osteoporosis, and a high fracture risk. Replacement with estrogen prevents this bone loss and reduces the risk of fracture. Estrogen uses two mechanisms to exert this effect: it inhibits bone resorption by osteoclasts and stimulates bone formation by osteoblasts. While the antiresorptive actions of estrogen arise from the inhibition of the MAP kinase JNK, the mechanism of its effect on the osteoblast remains unclear. Here we show that the osteoblast-directed anabolic action of estrogen occurs, at least in part, through an intermediary, oxytocin (OT), produced by bone marrow osteoblasts in response to estrogen.

Last Modified: 7/27/2016