Mechanical force inhibits osteoclastogenic potential of human periodontal ligament fibroblasts through OPG production and ERK-mediated signaling

Periodontal ligament and gingival fibroblasts play important roles in bone remodeling. Periodontal ligament fibroblasts stimulate bone remodeling while gingival fibroblasts protect abnormal bone resorption. However, few studies had examined the differences in stimulation of osteoclast formation between the two fibroblast populations. The precise effect of mechanical forces on osteoclastogenesis of these populations is also unknown. This study revealed that more osteoclast-like cells were induced in the co-cultures of bone marrow cells with periodontal ligament than gingival fibroblasts, and this was considerably increased when anti-osteoprotegerin (OPG) antibody was added to the co-cultures. mRNA levels of receptor activator of nuclear factor-kappaB ligand (RANKL) were increased in both populations when they were cultured with dexamethasone and vitamin D3. Centrifugal forces inhibited osteoclastogenesis of both populations, and this was likely related to the force-induced OPG up-regulation. Inhibition of extracellular signal-regulated kinase (ERK) signaling by a pharmacological inhibitor (10 μM PD98059) or by siERK transfection suppressed the force-induced OPG up-regulation along with the augmentation of osteoclast-like cells that were decreased by the force. These results suggest that periodontal ligament fibroblasts are naturally better at osteoclast induction than gingival fibroblasts, and that centrifugal force inhibited osteoclastogenesis of the periodontal fibroblasts through OPG production and ERK activation.