Fig. 7
IL-6 deletion partially rescues the sex-specific difference in corticalization in Dmp1Cre.Socs3 f/f mice. a Representative images of the top slice from the femoral metaphysis of 12-week-old female and male Dmp1Cre.Socs3 f/f and Dmp1Cre.Socs3 f/f. IL-6 −/− littermates. b Cortical porosity (box plots with whiskers showing minimum and maximum values) in the femoral metaphysis of female and male Dmp1Cre.Socs3 f/f and Dmp1Cre.Socs3 f/f. IL-6 −/− littermates; n per group is shown below the graph; **p < 0.01 for comparison shown, determined by two-way ANOVA with Sidak post-hoc test. c Calcein labeling in the corticalization zone in male Dmp1Cre.Socs3 f/f and Dmp1Cre.Socs3 f/f. IL-6 −/− littermates on the lateral side of the tibial metaphysis (boxed region shown (d)). c Representative images showing the morphology of longitudinal sections of the lateral side of the tibial metaphysis in control female mice, Dmp1Cre.Socs3 f /f females, Dmp1Cre.Socs3 f /f males, and Dmp1Cre.Socs3 f/f .IL-6 −/− males. Scale bar = 100 µm. Note the change in corticalization at the right hand side (lateral edge) of the metaphysis; yellow boxes indicate the regions shown (c). e Schematic diagram illustrating that cytokines acting on receptors on the cell surface of Dmp1Cre-expressing cells require inhibition of STAT3 signaling by SOCS3 to promote corticalization. In Dmp1Cre.Socs3 f/f mice, this is lost, leading to delayed corticalization; this delay is overcome by androgens through an interleukin-6 (IL-6)-dependent action. f Schematic diagram illustrating the changes in bone cell activity in male (blue line) and female (red line) mice as they age including the theoretical threshold of remodeling (horizontal black line) below which bone resorption is restrained by SOCS3 in Dmp1Cre +ve cells
