Fig. 1.

New biological approaches to retention. a) Sclerostin is a protein released by osteocytes and cells of the periodontal ligament, which blocks the maturation of pre-osteoblasts into bone-forming osteoblasts. Pre-osteoblasts also express RANKL, which can stimulate osteoclasts to resorb bone. Sclerostin also regulates mineralisation by late osteoblasts. Therefore, blocking sclerostin activity using romosozumab, a humanised monoclonal antibody that inhibits sclerostin, stimulates bone formation. b) Stimulation of RANK on the osteoclast surface by RANKL is essential for osteoclast formation and bone resorption. RANK is also packaged into extracellular vesicles (EVs) and released by osteoclasts. These RANK-EVs can interact with RANKL to competitively inhibit the interaction between RANKL and RANK on the osteoclast surface. In addition, when RANK-EVs interact with RANKL proteins on the pre-osteoblast surface, they stimulate a RANKL reverse signalling pathway that promotes bone formation