‘Educated’ Osteoblasts Reduce Osteoclastogenesis in a Bone-Tumor Mimetic Microenvironment

Breast cancer (BC) metastases to bone disrupt the balance between osteoblasts and osteoclasts, leading excessive resorption. We identified a novel subpopulation of with tumor-inhibitory properties, called educated (EOs). Here we sought examine effect EOs on osteoclastogenesis during tumor progression. hypothesized that affect osteoclast development in bone-tumor niche, suppressed pre-osteoclast fusion Conditioned media (CM) was analyzed for protein expression factors receptor activator nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG), necrosis alpha (TNFα) via ELISA. were co-cultured pre-osteoclasts mimetic matrix assess Pre-osteoclasts tri-cultured plus metastatic BC cells assessed tartrate-resistance acid phosphatase (TRAP)-positive, multinucleated (≥3 nuclei), mature osteoclasts. Tumor-bearing murine tibias stained TRAP determine number in-vivo. EO CM expressed reduced amounts soluble TNFα OPG compared naïve osteoblast CM. Osteoclasts formed presence smaller less number. Upon co-culture matrix, 50% reduction TRAP-positive osteoclasts observed. The tibia mice inoculated had per surface bones increased numbers cells. These data suggest reduce imply provide protective against resorption BC.