Site-Specific alterations in bone characteristics and mechanical properties in MYO9B-Deficient mice

Myosin IXB (MYO9B) is an unconventional class IX myosin expressed in bone cells that plays a role in normal skeletal growth, potentially due to MYO9B's interaction with IGF-1 signaling in osteoblasts. However, the role of MYO9B in determining jawbone characteristics has not been investigated. The objectives of this study were to investigate the effects of MYO9B knockout on the characteristics of the mandible and femur in young mice and to extend understanding of the role of MYO9B knockdown in osteoblastic IGF-1 signaling. C57BL/6 background MYO9B KO mice were generated. Sixty-one mice (30 male and 31 female, 12 weeks old) were assigned to either the WT (n = 31) or KO (n = 30) group. After euthanization, hemi-mandibles and femurs were dissected and scanned using microcomputed tomography to assess bone volumetric, tissue mineral density (TMD), geometric, and growth plate characteristics. A non-destructive dynamic mechanical analysis (DMA) was then performed using non-destructive oscillatory compression and bending on the hemi-mandible and femur, respectively. Finally, static bending was applied to the femur until fracture. MYO9B KO significantly worsened the characteristics of the femur by reducing length (8.76 %), bone mass (19.15 %), volume (19.12 %), geometry (56.32 %), and mechanical (41.59 %) parameters compared to the WT group. The growth plate in the KO group was also abnormally thinner, with a smaller bone fraction and lower TMD. In contrast, mandibular bone was not significantly different between MYO9B WT and KO mice. In vitro examination of MYO9B-deficient osteoblasts confirmed that loss of MYO9B resulted in altered expression, activation, and trafficking of IGF1R, leading to diminished IGF-1 signaling. These results suggest that site-specificity may arise due to differing roles of IGF-1 in growth of jaw versus appendicular bone.