Keynote Address: Osteoblasts Play Central Role in Pathogenesis of Periodontal Bone Loss

Body: The impact of leukocytes on periodontal pathogenesis is well known. The role of osteoblast-lineage cells has not been characterized. We demonstrated that periodontal infection induces nuclear localization of NF-kB in osteoblasts and osteocytes. Inactivation of NF-kB in these cells completely blocked bacteria-induced bone loss without affecting the level of inflammation. This occurred through two mechanisms; reduced expression of RANKL in osteoblasts/osteocytes leading to decreased osteoclast numbers, and inhibition of bone formation to reduce bone coupling. The latter mechanism inhibits repair of osteolytic lesions to magnify the effects of bone loss. NF-kB was shown to bind to the promoter region of bone matrix proteins and directly inhibit transcription of osteocalcin and bone sialoprotein. NF-kB blocked BMP-stimulated RUNX2 binding to the osteocalcin promoter and also blocked wnt-stimulated beta-catenin binding to the osteocalcin promoter. This represents a novel inhibitory mechanism whereby inflammation through NF-kB suppresses the expression of bone matrix proteins in osteoblasts.