However, despite the lack of correlation with birth weight, we did identify a statistically Gefitinib clinical trial significant
negative correlation between PHLDA2 expression and linear growth rate in the 58 infants who underwent ultrasound scanning at 19 and 34 weeks. There was also a weak negative correlation between placental PHLDA2 and crown heel length at birth and also height at age 4, both of which might be anticipated to have a relationship with pre term femoral length. While these measurements did not reach significance, DXA data obtained at 4 years did reveal an inverse correlation between placental PHLDA2 expression and bone mineral content [31]. These data suggest that PHLDA2 may act to restrict skeletal growth and this restricted growth in utero has post natal consequences for skeletal integrity. As with birth weights, the lack of significant negative correlation of PHLDA2 expression with crown heel length at birth and height at age 4 might be explained by the imprecision
of measurements taken on a single occasion over that obtained from scan data. It may well be that with a larger cohort these negative trends will achieve significance. We have previously reported a direct causative effect between high PHLDA2 and late onset growth restriction in an animal model, which we attributed to placental insufficiency [23] and [24]. Data from an animal model employing bilateral uterine vessel ligation to mimic GSK1120212 order placental insufficiency suggests a link between suboptimal fetal growth and postnatal bone density [32]. PHLDA2 may act specifically to
limit the transport of factors required for skeletal growth, for example by limiting calcium transport. Alternatively, PHLDA2 may indirectly affect calcium and bone metabolism through its role in regulating the placental hormones [24] involved in driving the maternal adaptations to pregnancy, which include increased maternal bone turnover. A third possibility is that PHLDA2 acts intrinsically to limit bone growth. PHLDA2 is expressed in human chondrocytes [33] and high expression of PHLDA2 has recently Farnesyltransferase been reported in hypertrophic mouse chondrocytes, as compared to proliferative/resting chondrocytes [34]. Animal models will play an important role in distinguishing between an intrinsic or extrinsic mechanism for limiting skeletal growth. Whatever the mechanism turns out to be, we have identified a potential role for PHLDA2 in restricting early skeletal growth, which has post natal consequences for skeletal integrity. In contrast to the negative relationship with fetal femur growth, PHLDA2 was positively associated with change in abdominal circumference from 19 to 34 weeks.
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