Fig. 2: Osteoblast-specific Hsd11b1 knockout mice are resistant to high-fat diet-induced trabecular bone loss and systemic metabolic disorders.
From: Targeting osteoblastic 11β-HSD1 to combat high-fat diet-induced bone loss and obesity
a Fluorescent immunohistochemistry analysis of 11β-HSD1 expression in bone cells of wild-type mice high-fat diet (HFD, n = 9) or chow diet (Chow, n = 9) for 16 weeks. Left: representative fluorescent images. Right: the ratio of 11β-HSD1-positive cells in either osteoblast lineage cells (Osx+ and Ocn+) or osteoclast lineage cells (Oscar+ and Ctsk+). Scale bar=50 μm. b The Hsd11b1 mRNA expression in osteoblast precursors (Osx+Ocn-) and osteoblasts (Osx+Ocn+) harvested from bone of mice with HFD (n = 5) or Chow (n = 5). c The constructing strategy. d Experimental design of osteoblast-specific Hsd11b1 knockout mice (Ob-CKO) and their littermates (WT mice) fed with HFD or Chow. e Systemic adrenocorticotropic hormone (ACTH) and corticosterone (n = 10 for Ob-CKO, n = 6 for WT). f Skeletal mRNA expression of the 11β-HSD1 gene (Hsd11b1) and the glucocorticoid target gene Glucocorticoid-induced leucine zipper (Gilz) (n = 8 for Ob-CKO, n = 6 for WT). g–j The micro-CT analysis and bone histometric analysis (n = 10 for Ob-CKO, n = 6 for WT). The data was normalized by WT-Chow group. g The trabecular bone microstructure. h The trabecular bone volume/total volume (Tb. BV/TV) and trabecular bone density (Tb. v. BMD). i The calcein double labeling. j The quantitative analysis of mineral apposition rate (MAR) and bone formation rate per bone surface (BFR/BS). k–m Weight gain, food intake and adipose tissues (n = 10 for Ob-CKO, n = 6 for WT). *P < 0.05, **P < 0.01 when HFD vs. Chow at the same genotype. k: Weight gain. The data was normalized by baseline. l: Food intake. m Weights and representative photographs of gonadal white adipose tissues (gWAT). n–p Glucose handling tests (n = 8 for Ob-CKO, n = 6 for WT). *P < 0.05, **P < 0.01, ***P < 0.001 when HFD vs. Chow at the same genotype. n Fasting blood glucose. o Insulin tolerance test (ITT). p Oral glucose tolerance test (oGTT). Note: Data were presented as mean value ± SEM for (b, e, f, h, j–p). All samples are biologically independent samples. Statistical significance was calculated using one-way ANOVA followed by Tukey’s post-hoc test (a) and two-way ANOVA followed by Sidak’s multiple comparisons test (b, e–p). All tests were two-sided.
