F‐Spondin Inhibits Migration and Differentiation of Osteoclastic Precursors

Background: Clinically, severe cemental resorption is a rare consequence of periodontitis, although alveolar bone resorption by osteoclasts is one of the main pathologic changes. F‐spondin is a secreted neuronal glycoprotein that localizes to the cementum. F‐spondin is among the cementum‐specific factors in periodontal tissue that have been reported. However, the effects of F‐spondin on osteoclastogenesis have not yet been established. We examined the effects of F‐spondin on stages of osteoclastogenesis, migration, and differentiation in a mouse osteoclastic precursor model, RAW 264 cells. Methods: RAW 264 cells were treated with recombinant F‐spondin. Macrophage colony stimulating factor (M‐CSF)–induced cell migration was examined by migration assay performed with cell culture inserts. Osteoclastic differentiation was measured by counting tartrate‐resistant acid phosphatase (TRAP)–positive multinucleated cells. Results: In a transmigration assay, F‐spondin significantly downregulated M‐CSF–induced cell migration. Further, F‐spondin significantly reduced the number of receptor activator of nuclear factor‐kappa B ligand–induced TRAP‐positive multinucleated cells. The receptor‐associated protein, an antagonist of the low‐density lipoprotein (LDL) receptor family, blocked the effects of F‐spondin on M‐CSF–induced migration. The suppressive effect of F‐spondin on M‐CSF–induced cell migration was blocked by knockdown of LDL receptor–related protein 8 (LRP8), a member of the LDL receptor family. Conclusions: Our findings suggest that F‐spondin downregulates recruitment to the root side of periodontal tissue via LRP8 and inhibits differentiation of osteoclastic precursors. It is suggested that F‐spondin is essential to protect the root surface from resorption.