Camphoric acid stimulates osteoblast differentiation and induces glutamate receptor expression

We found that camphoric acid significantly stimulated the differentiation of mouse osteoblastic MC3T3-E1 subclone 4 cells, as indicated by the induction of markers of osteoblastic differentiation. To elucidate the mechanism of action of camphoric acid in osteoblast differentiation, we evaluated the induction of transient receptor potential (TRP) cation channel family members and glutamate signaling molecules. TRPM7 and TRPV1 were highly expressed, but their expression was unaffected by camphoric acid. Camphoric acid is structurally similar to glutamate receptor ligands and significantly induced the expression of NMDAR1, GluR3/4, and mGluR8. However, camphoric acid exhibited weak regulatory activity toward glutamate receptors in a radioligand binding assay. Camphoric acid also significantly induced the activation of NF-kappaB and AP-1. Together, these data suggest that the stimulatory effect of camphoric acid on osteoblast differentiation was the result of its ability to induce mRNA expression of glutamate signaling molecules and to activate transcription factors.