Fig. 1: Exogenous cyclic loading-induced increases in bone mass and strength are suppressed in both genetically spontaneous and experimentally-induced T2D mice.

a The flow diagram of the experimental protocol, including the establishment of the genetically spontaneous and experimentally-induced male T2D mice, i.e., the KK-Ay mice and high-fat diet/streptozotocin-treated (HFD + STZ) mice, and subsequent application of cyclic compressive mechanical loading on tibiae for 2 weeks. The left tibia was subjected to daily physiological mechanical loading with 1200 cycles/day, and the contralateral right tibia was not subjected to cyclic loading and served as a control. b The linear correlation between the applied loads and strains on the antemedial surface of the mouse tibia in the non-diabetes, KK-Ay, and HFD + STZ groups. c A waveform of cyclic ramp loading at 4 Hz was applied with the identical tensile strain (1455 µε) generated on the antemedial surface by applying cyclic compressive loading with 9.0 N, 6.8 N, and 7.9 N on the mouse tibia in the non-diabetes, KK-Ay, and HFD + STZ groups, respectively. d Three-dimensional reconstructed micro-CT results showing proximal tibial trabecular bone microarchitecture in mice of the non-diabetes, KK-Ay and HFD + STZ groups. e Two-dimensional hematoxylin-eosin (H&E) staining images showing trabecular area microstructure in the proximal tibia. f, g Micro-CT results showing cortical bone thickness and cortical porosity. h, i Comparison of the whole-bone mechanical properties via the three-point bending testing and local tissue-level material properties via the nanoindentation testing. Graphs represent mean ± SD (n = 8 mice per group). *P < 0.05, **P < 0.01, and ***P < 0.001 by two-way ANOVA with Bonferroni’s post test. Specific P values are provided in the Source Data file. Scale bar: e 50 μm.