No Evidence for a Bone Phenotype in p21/CIP1 Knockout Mice under Normal Physiological Conditions

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 199-233-Bone Biology
Basic/Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-210
Hongrun Yu1, Heather Watt1 and Subburaman Mohan*2
1JL Pettis Memorial VA Medical Center, Loma Linda, CA, 2Loma Linda Univ, Loma Linda, CA
p21(WAF1/CIP1) is a well characterized cyclin-dependent kinase (cdk) inhibitor that has been implicated in the regulation of cell cycle control, apoptosis and differentiation.  Based on previous in vitro findings that: 1) p21 is down regulated during osteoblast differentiation and acts as a break on osteoblast proliferation and differentiation (Bellosta et al., 2003), 2) p21 is a transcriptional target of transcription factors, p53 and Runx2, which are master regulators of osteoblast development (Westendorf et al., 2002), and 3) BMP-4 effects on osteoblast differentiation are mediated in part via regulation of p21 expression (Chang et al., 2009), we proposed the hypothesis that p21 is an important regulator of osteoblast functions and skeletal development in vivo.  To test this hypothesis, we employed p21 deficient mice that were generated by targeted disruption of the p21 gene.  p21+/- mice purchased from Jackson Laboratory were intercrossed to generate homozygous p21-/- knockout (KO) and their littermate p21+/+ wild type (WT) control mice. Bone mass parameters were measured at 6 and 12 weeks of age by PIXImus.  Body weight was not significantly different between KO (n=13) and WT (n=8) mice either at 6 or 12 weeks of age.  Surprisingly, neither total body BMD nor BMD at individual skeletal sites (femur, tibia and vertebra) was significantly different between p21 KO and WT mice at 6 or 12 weeks of age.  Bone size parameters were also not different between the two genotypes.  In order to determine if the lack of p21 influences trabecular microarchitecture, the femoral metaphysis of KO (n=8) and WT (n=7) mice wasanalyzed at 12 weeks of age using microCT.  We found that trabecular bone volume adjusted for total volume in p21 KO mice (94±12 % of WT) was not different from that of WT mice.  Accordingly, there were no significant differences in trabecular number (97±6% of WT), trabecular thickness (95±4% of WT) or trabecular separation (103±7% of WT) between the KO and WT mice.  Based on these data, we conclude that mice with a targeted disruption of p21 exhibits a normal skeletal phenotype, thus suggesting that p21 functions are not essential for peak bone mass accrual under normal physiological conditions.   

Nothing to Disclose: HY, HW, SM

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm