“Osteoimmunology”is a continuously evolving area of scientific investigation. The term osteo-immunology specifically refers to the cross-regulation between bone cells and the immune system. One of the most important immune-related molecules involved in bone homeostasis is the Receptor Activator of Nuclear Factor κB Ligand (RANKL). RANKL has been described as the “master switch regulator” of osteoclastogenesis. Since bone homeostasis is a balance between bone formation (osteoblastogenesis) and bone resorption (osteoclastogenesis), understanding the regulatory mechanisms between these phases may provide greater insight into bone diseases where the scale is tipped in favor of resorption. Since periodontitis is an inflammatory disease characterized by alveolar bone loss, controlling the expression of RANKL in the periodontal lesion may be a useful treatment approach.
Osteoblasts express RANKL on their cell membrane. When this ligand binds to the RANKL receptor on a pre-osteoclast, it signals the cell to differentiate into an active osteoclast. The decoy receptor for RANKL, called osteoprotegerin, blocks this activation mechanism, thus helping to maintain bone homeostasis. In periodontitis, the ratio of RANKL to osteoprotegerin increases, whereas in health, the ratio is decreased. This ratio appears to be more important in identifying bone resorbing sites than the concentration of either RANKL or osteoprotegerin alone. What is known about RANKL and the periodontal lesion?
Gingival fibroblasts produce osteoprotegerin, which may help prevent bone resorption in the earlier stages of periodontal disease where the lesion is primarily confined to an area beneath the epithelium
Osteoblasts and periodontal ligament fibroblasts express RANKL on their cell membrane. T Cells not only express membrane bound RANKL, but also secrete it in soluble form. The pro-inflammatory cytokines interleukin-1β and interleukin-6, interleukin-11, interleukin-17, Tumor Necrosis Factor-α and the eicosanoid Prostaglandin E2 signal these cells to express membrane-bound RANKL, and the T Cell to secrete RANKL. Recall that these molecules have already been shown to be increased in the periodontal lesion and indirectly involved in periodontal bone loss. Thus, when the lesion has advanced toward the periodontal ligament and alveolar bone, the up-regulation of RANKL may lead to bone loss and subsequent deepening of the periodontal pocket. In such a scenario, it appears that the T Cell plays a significant role in bone resorption.
The concentrations of osteoprotegerin and RANKL are controlled not only by the cytokines listed above but also by oseotrophic hormones such as glucocortcoids and parathyroid hormone which inhibit osteoprotegerin and increase RANKL production. Estrogen appears to inhibit RANL and RANKL-stimulated osteoclastogenesis.