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

Abstract

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.

Callus formation is related to the expression ratios of estrogen receptors-alpha and -beta in ovariectomy-induced osteoporotic fracture healing

“…The differences in ER protein expression between the SHAM and OVX groups are consistent with the callus size and gene expression results, indicating the impaired response of fracture healing in the OVX group might be partly due to delayed arrival of the progenitor cells, angiogenesis and inferior circulation [5,42]. In contrast to ER-b gene over expression in other OVX animal models with cortical bone defects [17] and no fracture [19], our findings in both gene expression and protein expression may suggest that the impairment in early inflammation phase of endochondral ossification has caused the difference in ER presence, leading to delayed consolidation as shown by the mechanical test results.…”

“…It was also reported previously that the expression of ER-b would be higher in the OVX group throughout the healing process indicating the possible antagonistic function of ERb to ER-a in a different OVX-induced bone defect model [18]. However, the different patterns of expression in terms of the surging time [17,18] compared to the present study might be explained by the different animal models as closed femoral fractures would heal by endochondral ossification as compared to cortical drill-hole defects that would heal predominantly by intramembranous ossification [32]. Together with the observations in ER expression shown by IHC, our results may suggest that the expression of ER in fracture callus may be an early response of fracture healing or an early stimulus driving subsequent processes that is impaired in OVX.…”

“…The relationships between the two subtypes of ER-a and ER-b have not been completely unraveled. However, in bone metabolism, possibly due to the high degree of similarity in the DNA binding domain and the low overall homology between two subtypes [1,15,25], ER-b would act to supplement the functions of the ER-a when ER-a is in short supply but antagonize ER-a when both are abundant [17,30]. Therefore, the relative amounts of each have a determining effect on osteogenic responses in bone metabolism.…”

“…To study the mid-shaft fracture on an osteoporotic animal model with focuses in ER expression patterns and fracture healing through endochondral ossification, bone defect [32] and open fracture models [17,18] were excluded for this study. A standard closed femoral fracture model following Einhorn's protocol [7] was chosen because it is the most accepted fracture model for its high clinical relevance.…”

Bioinformatics and Microarray Analysis of miRNAs in Aged Female Mice Model Implied New Molecular Mechanisms for Impaired Fracture Healing

“…A low-pass Gaussian filter was used to do the three-dimensional (3D) reconstructions of mineralized tissues (Sigma = 1.2, Support = 2). To distinguish the newly mineralized callus from the old cortices, different thresholds (low attenuation = 130, high attenuation = 220) were determined in 2D images using the established evaluation protocol to reconstruct the low- and high-density mineralized tissues [52]. The low-density tissues indicated newly formed callus, while the high-density tissues indicated old cortices and highly mineralized callus.…”