Fig. 8: Specific overexpression of SERCA2 in osteocytes suppresses the T2D-induced deterioration in bone mechano-responsiveness.

a The experimental protocol of the high-fat diet/streptozotocin treatment in SERCA2^flox/flox; DMP1-Cre (SERCA2 cKI) mice, and subsequent application of cyclic compressive loading (1200 cycles/day) on the tibiae. b–d Micro-CT scanning for showing trabecular bone architecture, cortical bone thickness, and cortical porosity in the proximal tibiae of SERCA2 cKI mice with high-fat diet/streptozotocin treatment subjected to subsequent exogenous cyclic loading. e Three-point bending testing showing whole-bone mechanical properties in the tibiae of SERCA2 cKI mice with high-fat diet/streptozotocin treatment. f Nanoindentation testing showing local material properties in the tibiae of SERCA2 cKI mice with high-fat diet/streptozotocin treatment. g, h Immunohistochemical staining showing the protein expression of RANKL and sclerostin in osteocytes in tibial cortical bone matrix of SERCA2 cKI mice with high-fat diet/streptozotocin treatment. i Representative TRAP staining to label osteoclasts on tibial bone surfaces, and the corresponding statistical result. j Representative toluidine blue staining to label osteoblasts on tibial trabecular bone surface, and the corresponding statistical result. k Representative calcein and alizarin red double labeling of tibial trabecular bone surfaces, and the corresponding statistical result. Graphs represent mean ± SD (n = 6 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 bars: g, h, j 20 μm; i 30 μm; k 50 μm.