Oxytocin is an anabolic bone hormone.
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-kappaB 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.
Department of Human Anatomy and Histology, University of Bari, 70124 Bari, Italy.
Roberto
R
Tamma
Graziana
G
Colaianni
Ling-ling
LL
Zhu
Adriana
A
DiBenedetto
Giovanni
G
Greco
Gabriella
G
Montemurro
Nicola
N
Patano
Maurizio
M
Strippoli
Rosaria
R
Vergari
Lucia
L
Mancini
Silvia
S
Colucci
Maria
M
Grano
Roberta
R
Faccio
Xuan
X
Liu
Jianhua
J
Li
Sabah
S
Usmani
Marilyn
M
Bachar
Itai
I
Bab
Katsuhiko
K
Nishimori
Larry J
LJ
Young
Christoph
C
Buettner
Jameel
J
Iqbal
Li
L
Sun
Mone
M
Zaidi
Alberta
A
Zallone
D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010121:Oxytocin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D016328:NF-kappa B; D010121:Oxytocin; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium