Diagram 1.

A schematic model showcasing the action of SLIT3 in bone remodeling. (A) Osteoclast-derived SLIT3 stimulates osteoblastic migration and proliferation in a paracrine manner, and suppresses osteoclastic fusion and differentiation in an autocrine manner. (B) Osteoclasts produce and secrete SLIT3 via binding of p50 NF-κB and p-CREB to the promoter regions of Slit3. SLIT3 stimulates β-catenin activity by dissociating from N-cadherin via ROBO1 and ROBO2 receptors in osteoblasts, and suppresses Rac via ROBO1 and ROBO3 receptors in osteoclasts. OC, osteoclast; OB, osteoblast; MCSF, macrophage colony-stimulating factor; Lef/Tcf, lymphoid enhancer-binding factor 1/T cell-specific transcription factor; RANKL, receptor activator of nuclear factor κB ligand.