Synergy between IL-6 and soluble IL-6 receptor enhances bone morphogenetic protein-2/absorbable collagen sponge-induced bone regeneration via regulation of BMPRIA distribution and degradation

摘要: Bone morphogenetic protein-2/absorbable collagen sponge (BMP-2/ACS) implants have been approved for clinical use to induce bone regeneration. We previously showed that exaggerated inflammation characterized by elevated level of inflammatory cytokines including TNF-α, IL-1β, and IL-6 has shown inhibit BMP-2/ACS-induced Furthermore, unlike the negative effects TNF-α seemed not affect BMP-2-induced osteoblastic differentiation marrow mesenchymal stem cells (BMSCs). hypothesized there may be a regulatory loop between BMP-2 singling Here, we established ectopic formation model in rats fund injection significantly increased mass. Consistent with this animal model, an vitro study demonstrated synergy soluble receptor (IL-6/sIL-6R) promotes human BMSCs through amplification BMP/Smad signaling. Strikingly, did activate osteoclast-mediated resorption IL-6/sIL-6R treatment activator NF-κB ligand (RANKL)-induced osteoclastic peripheral blood mononuclear (PBMCs) vitro. expression BMP receptors, but enhanced cell surface translocation IA (BMPRIA) inhibited degradation BMPRIA. Collectively, these findings indicate sIL-6R BMPRIA maintains stability expression, leading