Deletion of estrogen receptor beta accelerates early stage of bone healing in a mouse osteotomy model

• Published in: Osteoporosis international 2012-01, Vol.23 (1), p.377-389
• Main Authors: He, Y.-X., Liu, Z., Pan, X.-H., Tang, T., Guo, B.-S., Zheng, L.-Z., Xie, X.-H., Wang, X.-L., Lee, K.-M., Li, G., Cao, Y.-P., Wei, L., Chen, Y., Yang, Z.-J., Hung, L.-K., Qin, L., Zhang, G.
• Format: Article
• Language: English
• Subjects: Angiography; Animals; Beta; Biochemical markers; Biomarkers - blood; Biomechanical Phenomena; Bone (endochondral); Bone healing; Bone histomorphometry; Bone Remodeling - physiology; Bony Callus - blood supply; Bony Callus - diagnostic imaging; Bony Callus - physiology; Callus; Collagen; Collagen Type I - blood; Computed tomography; Data processing; Disease Models, Animal; Endocrinology; Energy; Estrogen Receptor beta - deficiency; Estrogen Receptor beta - genetics; Estrogen Receptor beta - physiology; Estrogen receptors; Estrogens; Female; Femoral Fractures - diagnostic imaging; Femoral Fractures - physiopathology; Femur; Femur - blood supply; Fracture Healing - physiology; Fractures; Mechanical properties; Medicine; Medicine & Public Health; Mice; Mice, Knockout; Neovascularization, Physiologic - physiology; Neurons; Original Article; Orthopedics; Ossification; Osteoporosis; Osteotomy; Peptide Fragments - blood; Peptides - blood; Polymerase chain reaction; Procollagen - blood; Real-Time Polymerase Chain Reaction - methods; Rheumatology; Rodents; vascularization; X-Ray Microtomography
• ISSN: 0937-941X; 1433-2965
• DOI: 10.1007/s00198-011-1812-x

Summary This study examined the role of estrogen receptor (ER) beta during mouse femoral fracture healing by employing ER knockout (KO) mice. The fracture healing in KO mice was enhanced in the early stage of neovascularization and the middle stage of endochondral ossification. Introduction This study was conducted to examine the role of ER beta during fracture healing. Methods Female ERbeta knockout (KO) mice (18 weeks old) and age-matched female wild-type (WT) mice underwent open osteotomy on the right femur. They were sacrificed at 1, 2, 4 and 6 weeks post-fracture. The sera and callus samples were subjected to the following analyses: micro-computed tomography (CT)-based angiography, micro-CT evaluation, histological examination, histomorphometry examination, real-time polymerase chain reaction (PCR) analysis, biochemical marker, and mechanical testing. Results Micro-CT-based angiography showed that the total vessel volume at the fracture site was larger in the KO group than the WT group at 1 and 2 weeks post-fracture. Micro-CT analysis revealed that the callus volume was significantly higher in the KO group from week 2 to week 4 post-fracture when compared with the WT group consistent with the histological data. Analysis of biochemical markers indicated that circulating P1NP levels in the KO mice were significantly higher than in the WT mice from week 2 to week 4 and that temporal expression of circulating C-terminal telopeptide of type I collagen (CTX) levels was also higher in the KO mice than in the WT mice. These results were consistent with quantitative real-time PCR analysis. The ultimate load, stiffness, and energy to failure were significantly higher in the KO mice than in the WT mice at week 4. Conclusions The fracture healing in KO mice was enhanced in the early stage of neovascularization and the middle stage of endochondral ossification, but not by the end of healing. Blockade of ERbeta can be considered as another therapeutic strategy for osteoporotic fracture and non-union fracture.