Fig. 6

Effects of β-catenin-linked Wnt signaling in A5 osteocytes on tumor progression. CN control (plain medium), CM conditioned medium, pl placebo, pL5 Lrp5 plasmids, and pβ-cat β-catenin plasmids. The single and double asterisks indicate P < 0.05 and P < 0.01, respectively. a–c Significant reductions in mammary tumor growth and bone degradation in the tibia in C57BL/6 mice by systemic administration of β-catenin-overexpressing osteocyte-derived CM. d–f Significant reductions in the number of TRAP-stained mature osteoclasts and the expression of NFATc1 and Cathepsin K in RANKL-stimulated osteoclasts by treatment with Lrp5- and β-catenin-overexpressing osteocyte-derived CM. Scale bar: 200 μm. g Schematic illustration of the mechanism regulating tumor-osteocyte interactions. In this diagram, Lrp5 and β-catenin in osteocytes inhibit tumor progression by decreasing the expression of tumor-promoting genes (TGFβ, CXCL1, and CXCL5) and increasing the expression of tumor-suppressing genes (p53, ANXA6, and TPM4) and apoptosis-inducing genes (Trail). In tumor cells, tumor-promoting genes (Lrp5, Runx2, MMP9, and Snail) were downregulated. Overexpression of Lrp5 and β-catenin also inhibited osteoclastogenesis by downregulating NFATc1 and cathepsin K