Osteoclast differentiation. Cells of the mylomonocytic lineage (appropriate sources for in vitro differentiation are cells from bone marrow, monocytes, spleen or RAW 264.7 cells) under the influence of macrophage-colony stimulating factor (M-CSF) and receptor activator of NFκB ligand (RANKL) differentiate into osteoclasts. Depicted above this differentiation pathway is the potential role for T lymphocytes in enhancing or fulfilling this process. Upon activation of osteoclasts following engagement of the T cell receptor (TCR), T lymphocytes may produce several factors that promote osteoclast formation (RANKL and IL-7) or the production of RANKL by fibroblast and stromal cells (for example, IL-1, IL-6, IL-17). Below the differentiation pathway, the inhibitory actions of T lymphocytes are presented. T lymphocytes produce a vast array of inhibitory molecules, and several of these are elevated in response to IL-4, IL-12, IL-15, IL-18, IL-23 and osteoprotegerin (OPG). GM-CSF, granulocyte macrophage-colony stimulating factor; sFRP, secreted Frizzled-related protein; OCIL, osteoclast inhibitory lectin.