Oxytocin is an anabolic bone hormone

R Tamma, G Colaianni, L Zhu… - Proceedings of the …, 2009 - National Acad Sciences
R Tamma, G Colaianni, L Zhu, A DiBenedetto, G Greco, G Montemurro, N Patano…
Proceedings of the National Academy of Sciences, 2009National Acad Sciences
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 …
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 Ca2+ 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.
National Acad Sciences