Pregnancy associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that cleaves insulin like growth factor binding protein-5 (IGFBP-5), the most abundant IGFBP in bone. Deletion of the Pappa2 gene reduces post-natal growth and skeletal size in mice. This research aimed to further understand the role of PAPP-A2 in skeletal physiology using mice with Pappa2 disrupted constitutively, spatially (in bone), or temporally (in adulthood). I demonstrate that PAPP-A2 produced in bone AND other tissues regulates post-natal growth and skeletal size. Constitutive Pappa2 deletion increases cortical bone mineral density (BMD), whereas disruption of Pappa2 in adulthood decreases trabecular BMD in males alone. PAPP-A2, therefore, appears to play age-specific and potentially site-specific roles. Currently, there is a need for anabolic agents for the treatment of diseases like osteoporosis, making PAPP-A2 an interesting avenue of research.
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Thesis advisor: Christians, Julian
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