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The cellular response of human gingival fibroblasts to a mechanical force is considered to be primarily anti-osteoclastic because they produce relatively high levels of osteoprotegerin. However, there is little information available on the effects of compression force on the production of osteoprotegerin and osteoclastic differentiation by these cells. In this study, we examined how mechanical force affects the nature of human gingival fibroblasts to produce osteoprotegerin and inhibit osteoclastogenesis.Human gingival fibroblasts were exposed to mechanical force by centrifugation for 90 min at a magnitude of approximately 50 g/cm2. The levels of osteoprotegerin, receptor activator of nuclear factor-κB ligand (RANKL), interleukin-1β and tumor necrosis factor-α were measured at various time-points after applying the force. The effect of the centrifugal force on the formation of osteoclast-like cells was also determined using a co-culture system of human gingival fibroblasts and bone marrow cells.Centrifugal force stimulated the expression of osteoprotegerin, RANKL, interleukin-1β and tumor necrosis factor-α by the cells, and produced a relatively high osteoprotegerin to RANKL ratio at the protein level. Both interleukin-1β and tumor necrosis factor-α accelerated the force-induced production of osteoprotegerin, which was inhibited significantly by the addition of anti-(interleukin-1β) immunoglobulin Ig isotype; IgG (rabbit polyclonal). However, the addition of anti-(tumor necrosis factor-α) immunoglobulin Ig isotype; IgG1 (mouse monoclonal) had no effect. Centrifugal force also had an inhibitory effect on osteoclast formation.Application of centrifugal force to human gingival fibroblasts accelerates osteoprotegerin production by these cells, which stimulates the potential of human gingival fibroblasts to suppress osteoclastogenesis. Overall, human gingival fibroblasts might have natural defensive mechanisms to inhibit bone resorption induced by a mechanical stress.