Biomechanical and Bone Material Properties of Schnurri‐3 Null Mice

Abstract

Schnurri‐3 (Shn3) is an essential regulator of postnatal skeletal remodeling. Shn3‐deficient mice (Shn3–/–) have high bone mass; however, their bone mechanical and material properties have not been investigated to date. We performed three‐point bending of femora, compression tests of L3 vertebrae. We also measured intrinsic material properties, including bone mineralization density distribution (BMDD) and osteocyte lacunae section (OLS) characteristics by quantitative backscatter electron imaging, as well as collagen cross‐linking by Fourier transform infrared microspectroscopy of femora from Shn3–/– and WT mice at different ages (6 weeks, 4 months, and 18 months). Moreover, computer modeling was performed for the interpretation of the BMDD outcomes. Femora and L3 vertebrae from Shn3–/– aged 6 weeks revealed increased ultimate force (2.2‐ and 3.2‐fold, p < .01, respectively). Mineralized bone volume at the distal femoral metaphysis was about twofold (at 6 weeks) to eightfold (at 4 and 18 months of age) in Shn3–/– (p < .001). Compared with WT, the average degree of trabecular bone mineralization was similar at 6 weeks, but increased at 4 and 18 months of age (+12.6% and +7.7%, p < .01, respectively) in Shn3–/–. The analysis of OLS characteristics revealed a higher OLS area for Shn3–/– versus WT at all ages (+16%, +23%, +21%, respectively, p < .01). The collagen cross‐link ratio was similar between groups. We conclude that femora and vertebrae from Shn3–/– had higher ultimate force in mechanical testing. Computer modeling demonstrated that in cases of highly increased bone volume, the average degree of bone matrix mineralization can be higher than in WT bone, which was actually measured in the older Shn3–/– groups. The area of 2D osteocyte lacunae sections was also increased in Shn3‐deficiency, which could only partly be explained by larger remnant areas of primary cortical bone. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

No Role of Osteocytic Osteolysis in the Development and Recovery of the Bone Phenotype Induced by Severe Secondary Hyperparathyroidism in Vitamin D Receptor Deficient Mice

“…Some evidence of premature ageing was found based on effects in lipid and carbohydrate metabolism, although the VDR ∆/∆ mice might not be an appropriate model for studying such effects because the older VDR mutants have a lean phenotype [20]. Moreover, there is no evidence that BMDD changes occur by ageing adult wild-type mice to a much older age than studied in the present work [21,22]. This suggests that we were able to observe dietary effects only, and we can generally rule out any significant influence of age on BMDD in the present work.…”

Skeletal phenotypes in secreted frizzled-related protein 4 gene knockout mice mimic skeletal architectural abnormalities in subjects with Pyle’s disease from SFRP4 mutations

“…We suggest that the normal resorption of entire trabeculae at the metaphyseal-diaphyseal junction does not occur in the absence of SFRP4, resulting in marrow cavity trabecularization within the diaphysis. Extensive trabecularization of the diaphyseal marrow cavity also occurs in adult mice with genetic disruptions of Kindlin3 , 45 Lrrk1 46 , Schnurri3 , 47 Sgpl1 , 17 , 48 Slc37a2 49 , and Vhl . 50 Consistent with our suggestion, diaphyseal trabeculae in adult Lrrk1 and Vhl KO mice contain remnants of calcified cartilage, presumably originating from the metaphyseal growth plate region.…”

Vitamin C Deficiency Deteriorates Bone Microarchitecture and Mineralization in a Sex-Specific Manner in Adult Mice

“…Histomorphometric evaluation of the mineralized bone volume near to the growth plate (primary md.BV/TV) as well as in the metaphyseal region (secondary md.BV/TV), which is typically used for histomorphometric evaluation of trabecular bone volume in mice, ( 19 ) was performed. For this purpose, the qBEI overview images (3.1 μm pixel resolution) were binarized using a gray‐level threshold corresponding to calcium concentrations beyond 5.2 wt % calcium, and pixels below this threshold were excluded from the analysis.…”