TY - JOUR
T1 - Oxytocin is an anabolic bone hormone
AU - Tamma, Roberto
AU - Colaianni, Graziana
AU - Zhu, Ling Ling
AU - DiBenedetto, Adriana
AU - Greco, Giovanni
AU - Montemurro, Gabriella
AU - Patano, Nicola
AU - Strippoli, Maurizio
AU - Vergari, Rosaria
AU - Mancini, Lucia
AU - Colucci, Silvia
AU - Grano, Maria
AU - Faccio, Roberta
AU - Liu, Xuan
AU - Li, Jianhua
AU - Usmani, Sabah
AU - Bachar, Marilyn
AU - Bab, Itai
AU - Nishimori, Katsuhiko
AU - Young, Larry J.
AU - Buettner, Christoph
AU - Iqbal, Jameel
AU - Sun, Li
AU - Zaidi, Mone
AU - Zallone, Alberta
PY - 2009/4/28
Y1 - 2009/4/28
N2 - 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.
AB - 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.
KW - Bone density
KW - Osteoblast
KW - Osteoclast
KW - Osteoporosis
KW - Pituitary hormones
UR - http://www.scopus.com/inward/record.url?scp=66349135343&partnerID=8YFLogxK
U2 - 10.1073/pnas.0901890106
DO - 10.1073/pnas.0901890106
M3 - Article
C2 - 19369205
AN - SCOPUS:66349135343
SN - 0027-8424
VL - 106
SP - 7149
EP - 7154
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 17
ER -