Bars represent the means ± SE (n = 6). *p < 0.05.

C control, SN sciatic neurectomy, L loading Loading reversed the sciatic neurectomy-induced increases in the percentage of sclerostin-positive osteocytes in the cortical bone of both the proximal and distal sites (Fig. 3a, b) and in the trabecular bone of both the primary and secondary spongiosa (Fig. 4a, b). However, loading reduced the percentage of sclerostin-positive osteocytes to a level FK228 solubility dmso significantly lower than that in controls only in the proximal cortical region and the secondary spongiosa. Discussion In the present study, we used the mouse unilateral tibia axial loading I-BET151 solubility dmso model [24, 25] to assess the effects of loading on both cortical and trabecular bone compartments in vivo. In cortical bone, short periods of dynamic loading, in addition to that engendered by habitual physical activity, MAPK inhibitor were associated with decreased osteocyte sclerostin staining and increased bone formation and bone volume at the proximal but not the distal site. In contrast, reduced loading due to sciatic neurectomy resulted in an increase in the percentage of sclerostin-positive osteocytes and decreased bone volume at both sites. In trabecular bone, exposure to the same artificial loading regimen induced a decrease in osteocyte sclerostin staining

and an increase in bone volume in the secondary but not the selleck products primary spongiosa. Sciatic neurectomy-related disuse caused an increase in osteocyte sclerostin staining and a decrease in bone volume in both primary and secondary spongiosa. The effects of sciatic neurectomy-related disuse on both cortical and trabecular bone were reversed by artificial loading, with a significant reduction in sclerostin expression, to below that seen in controls, at the proximal site and secondary spongiosa, respectively.

The analysis of loading-related strain levels, areas of new bone formed, and changes in the sclerostin status of osteocytes in cortical bone confirmed that sclerostin downregulation by loading was not uniform throughout the bone, and revealed that this was less closely associated with the magnitude of peak strain engendered than with the degree of subsequent local new bone formation. In the proximal cortical region, loading-related suppression of osteocyte sclerostin expression was linked to the area of loading-related newly formed bone. Loading-induced strain magnitude is frequently associated with subsequent bone formation, and at the proximal site, the strain distribution map we present, which is similar to that reported by others [30], was also related to the area of loading-related newly formed bone. These data are consistent with the results reported previously [6].