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. 2014 Nov 13;5(11):e1522. doi: 10.1038/cddis.2014.480

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Copyright © 2014 Macmillan Publishers Limited

Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0

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Increased trabecular bone in KO mice. To ascertain whether differences in bone formation persisted as the mice aged, 3-month-, 1–year- and 2-year-old mouse femurs from WT, Het and KO were subjected to microCT analysis. (a) Representative microCT generated longitudinal sections of hind limb femurs demonstrated increased number and penetration into the diaphysis of trabeculae (dotted lines) in the KO animal at 3 months. (b) Increased trabeculae observed in 200 16-μm slices in cross-section of the KO mouse. (c) Analysis of trabecular bone (red circle in b) shows a significant increase in mineralized bone volume/total bone volume (BV/TV), trabecular number (Tb.n.) and connectivity density (Conn.Dens., an assessment of the number of connected structures in the trabecular bone network) in KO mice compared with WT. There was no difference in bone quality (mineral density) of trabeculae. (d) Cortical bone BV/TV and mean density showed no significant difference. (e) Trabecular analysis by microCT at 1 year of age showed equalization of BV/TV, which persisted through 2 years (f). (n=3 for each genotype; **P≤0.01; NS, not significant; scale bar, 500 μm)