373 Polycytin-2 function in cortical bone development

Thursday, March 22, 2012: 2 p.m. - 3:15 p.m.
Presentation Type: Poster Session
C.J. HAYCRAFT, and S.G. JOSEPH, Craniofacial Biology, Medical University of South Carolina, Charleston, SC
Objectives: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of a growing number of human disorders linked  to the primary cilium due to the localization of the affected protein.  Mutations in polycystin-1 (PC1) or polycystin-2 (PC2) cause ADPKD and the two transmembrane proteins have been shown to function as a mechanosensitive complex.  While the requirement for cilia during bone development has been demonstrated, the requirement for PC2 in osteoblast differentiation and bone development has yet to be investigated. Recent studies have shown that loss of PC1 leads to changes in osteoblast gene expression and trabecular and cortical bone thickness. The objective of the current study is to asses the requirement for PC2 in bone formation and modeling using conditional mouse mutants.  

Methods: To remove PC2 from the appendicular skeleton, mice expressing a conditional allele of PC2 were mated to mice expressing Cre recombinase in the developing limbs (prx1cre).  The resulting conditional mutant mice and littermate controls were analyzed using microCT to examine cortical and trabecular bone parameters. 

Results: In the conditional mutant mice, PC2 was efficiently removed from the developing bones on Western blots.  In contrast to the role of PC1 in the skeleton, loss of PC2 leads to an increase in cortical bone thickness in the tibia when analyzed by microCT.  The increased cortical bone thickness is apparent as early as 1 month of age.  No significant changes in trabecular bone morphology were observed. 

Conclusions: Overall, we conclude that PC2 is essential in the developing long bones for proper cortical bone architecture but is not essential for osteoblast differentiation.

This abstract is based on research that was funded entirely or partially by an outside source: NIH 5 P30 DK074038

Keywords: Bone, Cell biology, Genetics, Growth & development and Osteoblasts/osteoclasts