Targeted Deletion of the Sclerostin Gene in Mice Results in Increased Bone Formation and Bone Strength

• DOI: 10.1359/jbmr.080216
• Publication Date: 2008-02-12T14:30:37Z
• Authors: Xiaodong Li; Michael S Ominsky; Qing-Tian Niu; Ning Sun; Betsy Daugherty; Diane D'Agostin; Carole Kurahara; Yongming Gao; Jin Cao; Jianhua Gong; Frank Asuncion; Mauricio Barrero; Kelly Warmington; Denise Dwyer; Marina Stolina; Sean Morony; Ildiko Sarosi; Paul J Kostenuik; David L Lacey; W Scott Simonet; Hua Zhu Ke; Chris Paszty
• Keywords: Sclerostin; Osteocyte; Densitometry

Sclerosteosis is a rare high bone mass genetic disorder in humans caused by inactivating mutations SOST, the gene encoding sclerostin. Based on these data, sclerostin has emerged as key negative regulator of mass. We generated SOST knockout (KO) mice to gain more detailed understanding effects deficiency bone.Gene targeting was used inactivate and generate line KO mice. Radiography, densitometry, microCT, histomorphometry, mechanical testing were characterize impact male female Comparisons made between same sex wildtype (WT) mice.The results for similar, with differences only magnitude some effects. had increased radiodensity throughout skeleton, general skeletal morphology being normal appearance. DXA analysis lumbar vertebrae whole leg showed that there significant increase BMD (>50%) at both sites. microCT femur volume significantly trabecular cortical compartments. Histomorphometry revealed osteoblast surface no change osteoclast The formation rate (>9-fold) distal femur, well endocortical periosteal surfaces midshaft. Mechanical strength sites mice.SOST have phenotype characterized marked increases BMD, volume, formation, strength. These show powerful, evolutionarily conserved pathway acts bone.