PAPP-A2 expression by osteoblasts is required for normal postnatal growth in mice

Area of Science:

• Endocrinology
• Bone Biology
• Genetics

Background:

• Pregnancy Associated Plasma Protein-A2 (PAPP-A2) is a protease that cleaves insulin-like growth factor binding protein-5 (IGFBP-5).
• IGFBP-5 is the most abundant IGFBP in bone.
• Pappa2 deletion in mice leads to reduced postnatal growth and bone length.

Purpose of the Study:

• To determine if locally produced PAPP-A2 is necessary for normal bone growth.
• Investigate the role of osteoblast-specific PAPP-A2 in postnatal development.

Main Methods:

• Conditional Pappa2 deletion in osteoblasts using Sp7 (Osterix) promoter-driven Cre recombinase.
• Measurement of body mass and tail length at multiple ages (3, 6, 10, 12 weeks).
• Analysis of bone dimensions at 12 weeks of age.

Main Results:

• Osteoblast-specific Pappa2 deletion significantly reduced body mass, tail length, and linear bone dimensions.
• PAPP-A2 produced by Sp7-expressing cells is demonstrably required for normal growth.
• Constitutive Pappa2 deletion showed more pronounced effects than osteoblast-specific deletion, suggesting other PAPP-A2 sources impact postnatal growth.

Conclusions:

• Locally produced PAPP-A2 is indispensable for normal bone growth.
• PAPP-A2 expression in osteoblasts plays a critical role in skeletal development.