We previously demonstrated, using osteoblastic MC3T3-E1 cells, that P2Y2 purinergic receptors are involved in osteoblast mechanotransduction. In this study, our objective was to further investigate, using a knockout mouse model, the roles of P2Y2 receptors in bone mechanobiology. We first examined bone structure with micro-CT and measured bone mechanical properties with three point bending experiments in both wild type mice and P2Y2 knockout mice. We found that bones from P2Y2 knockout mice have significantly decreased bone volume, bone thickness, bone stiffness and bone ultimate breaking force at 17 week old age. In order to elucidate the mechanisms by which P2Y2 receptors contribute to bone biology, we examined differentiation and mineralization of bone marrow cells from wild type and P2Y2 knockout mice. We found that P2Y2 receptor deficiency reduces the differentiation and mineralization of bone marrow cells. Next, we compared the response of primary osteoblasts, from both wild type and P2Y2 knockout mice, to ATP and mechanical stimulation (oscillatory fluid flow), and found that osteoblasts from wild type mice have a stronger response, in terms of ERK1/2 phosphorylation, to both ATP and fluid flow, relative to P2Y2 knockout mice. However, we did not detect any difference in ATP release in response to fluid flow between wild type and P2Y2 knock out osteoblasts. Our findings suggest that P2Y2 receptors play important roles in bone marrow cell differentiation and mineralization as well as in bone cell mechanotransduction, leading to an osteopenic phenotype in P2Y2 knockout mice.

Ten weeks of ACE at 70% VO in high motor complete SCI improves aerobic capacity, community mobility, and metabolic profiles independent of changes in body composition.

PurposeFractures are the second most common presentation of child abuse following soft-tissue bruising and burns. It is often difficult to determine potential abuse in a child presenting with a non-rib fracture(s) and without soft-tissue injuries.MethodsOne hundred and fifteen consecutive patients aged ≤2 years who presented with a fracture between January 2010 and June 2012 to our emergency department (ED) or pediatric fracture clinic were retrospectively analyzed. Statistical analyses were carried out for non-accidental fractures based on age (<1 year vs 1–2 years), location of presentation (ED vs pediatric fracture clinic), type of long bone fracture, number of fractures, and patient demographics.ResultsFractures in 19 of 115 (17 %) patients were reported as non-accidental trauma (NAT). Eighty (70 %) of the 115 patients first reported to the ED. Thirty-two percent of fractures in children aged <1 year and 5 % of fractures in children aged 1–2 years were reported as NAT (p < 0.001). Sixteen of 19 (84 %) patients reported for abuse had multiple fractures; 15 of these patients were aged <1 year. Eight of 11 (73 %) reported femoral fractures were transverse fractures. Corner fractures (12) only occurred in children aged <1 year and never occurred in isolation; all of them were reported as NAT. Four of 60 patients (7 %) with commercial insurance and 15 of 55 patients (28 %) with Medicaid were reported as NAT.ConclusionsAge less than 1 year, multiple fractures, corner fractures, transverse fractures, and covered by Medicaid were the most common factors associated with reporting of NAT.