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Publication : Pappa2 deletion has sex- and age-specific effects on bone in mice.

First Author  Christians JK Year  2019
Journal  Growth Horm IGF Res Volume  44
Pages  6-10 PubMed ID  30445407
Mgi Jnum  J:310507 Mgi Id  MGI:6756857
Doi  10.1016/j.ghir.2018.10.006 Citation  Christians JK, et al. (2019) Pappa2 deletion has sex- and age-specific effects on bone in mice. Growth Horm IGF Res 44:6-10
abstractText  OBJECTIVE: In humans, loss-of-function mutations in the gene encoding pregnancy-associated pregnancy protein-A2 cause short stature and slightly reduced bone density. The goal of this study was to determine the effects of Pappa2 deletion on bone in mice. DESIGN: Pappa2 deletion mice and littermate controls were culled at 10, 19 or 30weeks of age and femurs were analysed by micro-computed tomography. Serum markers of bone turnover and insulin-like growth factor binding protein 5 (IGFBP-5), a proteolytic target of PAPP-A2, were measured by ELISA. RESULTS: At 10 and 19weeks of age, Pappa2 deletion mice had slightly reduced trabecular parameters, but by 19weeks of age, female deletion mice had increased cortical tissue mineral density, and this trait was increased by a small amount in deletion mice of both sexes at 30weeks. Cortical area fraction was increased in Pappa2 deletion mice at all ages. Deletion of Pappa2 increased circulating IGFBP-5 levels and reduced markers of bone turnover (PINP and TRACP 5b). CONCLUSIONS: PAPP-A2 contributes to the regulation of bone structure and mass in mice, likely through control of IGFBP-5 levels. The net effect of changes in bone formation and resorption depend on sex and age, and differ between trabecular and cortical bone.
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