Fig. 5

Schematic diagram of SLIT3 function upon LPS stimulation of OCPs. Committed myeloid precursor cells (monocytes/macrophages) with RANK-negative monocytes undergo commitment into RANK-positive monocytes, which is an osteoclast precursor cells (OCPs) in M-CSF response and differentiation into mononuclear pre-fusion osteoclast cells (pOCs) and multinucleated OCs (mOCs) is further modulated by RANKL and M-CSF signaling. However, LPS stimulation through TLR4 upregulates SLIT3/ROBO1 expression in OCPs, and this SLIT3-ROBO1 signaling raises the ratio of the C/EBP-β isoform LAP to LIP protein level, and induces MafB expression, leading to restrained osteoclast differentiation potential in RANKL-primed OCPs. Furthermore, SLIT3 induction concomitantly increases miR-218–2-3p expression, which directly inhibits the expression of RANK, and synergistically controls osteoclastic potential in OCPs