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.

Osteoblasts cultured on three-dimensional synthetic hydroxyapatite implanted on a chick allantochorial membrane induce ectopic bone marrow differentiation.

Osteoblast (OB) activities have been studied on hydroxyapatite three-dimensional (3D) scaffolds in comparison with traditional planar substrata. OBs cultured on 3D displayed increased proliferation, differentiation, and matrix protein synthesis, when compared to 2D cultures on the same substrata. Confluent cultures, however, could not be maintained for long, due to insufficient fluid diffusion within 3D scaffolds that impaired cell viability. Thus, confluent OB 3D cultures were implanted on the allantochorial membrane of chick embryos. Vessels from the embryo colonized the bone-like network giving rise in the presence of OBs to an ectopic bone marrow formation in the intratrabecular spaces. In the absence of OBs, when the biomaterial alone was implanted, blood vessels were still present but hematopoietic marrow was absent. In both cases osteoclasts (OCs) derived from the host were found on the implant surface. These results indicated that scaffolds with cells can be easily vascularized and confirmed the role of OBs in the definition of the microenvironment that induce blood marrow differentiation in the intratrabecular spaces.

Enhanced osteoclastogenesis in women after natural delivery.

In the pre-expulsive and expulsive phases of labor, oxytocin and several other osteoclastogenic mediators, such as prostaglandins and IL-6, are secreted in high concentrations. This study was undertaken to assess whether the peripheral blood obtained from healthy women after vaginal delivery contains a larger pool of osteoclast precursors compared with age- and gender-matched controls. Our results clearly show that the number and size of osteoclasts generated in vitro from osteoclast precursors isolated from women after delivery are significantly larger than those from controls. This finding can account for the decrease in bone mass that is often observed during the breastfeeding period and the concomitant release of high quantities of calcium in the milk. Further investigations are required to establish whether analysis of blood osteoclast precursors can be predictive of changes in bone remodeling in this setting.