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Title: Bone marrow oxytocin mediates the anabolic action of estrogen on the skeleton

item COLAIANNI, GRAZIANA - Mount Sinai School Of Medicine
item SUN, LI - Mount Sinai School Of Medicine
item DI BENEDETTO, ANDRIANA - Mount Sinai School Of Medicine
item TAMMA, ROBERTO - University Of Bari
item ZHU, LING-LING - University Of Bari
item Cao, Jay
item GRANO, MARIA - University Of Bari
item YUAN, TONY - Mount Sinai School Of Medicine
item COLUCCI, SYLVA - University Of Bari
item CUSCITO, CONCETTA - Mount Sinai School Of Medicine
item MANCINI, LUCIA - University Of Bari
item LI, JINHUA - Mount Sinai School Of Medicine
item NISHIMORI, KATSUHIKO - Tokyo University Of Agriculture & Technology
item BAB, ITAI - University Of Jerusalem
item LEE, HEON-JIN - Kyungpook National University
item IQBAL, JAMEEL - Mount Sinai School Of Medicine
item YOUNG, W. SCOTT - University Of Bari
item ROSEN, CLIFFORD - Maine Medical Center Research Institute (MMCRI)
item ZALLONE, ALBERTA - University Of Bari
item ZAIDI, MONE - Mount Sinai School Of Medicine

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/18/2012
Publication Date: 8/17/2012
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.