Regulation of osteoclast formation. In normal physiology, osteoclast formation is regulated by production of membrane-bound RANK-L/OPG-L and soluble OPG in stromal/osteoblastic cells under the influence of stimulators of resorption. In inflammatory states, activated T lymphocytes produce both membrane-bound and soluble RANK-L/OPG-L, which stimulates RANK on osteoclast precursor cells and initiates their differentiation into osteoclasts. IL-1, TNF, and PGE2 may also directly affect osteoclast precursors or mature osteoclasts.