<prompt> Answer this question truthfullyWhat is the explanation for osteoclasts and their formation?  <response>: <reason> Osteoclasts formation requires the presence of RANK ligand receptor activator of nuclear factor κβ and M-CSF Macrophage colony-stimulating factor. These membrane bound proteins are produced by neighbouring stromal cells and osteoblasts; thus requiring direct contact between these cells and osteoclast precursors.M-CSF acts through its receptor on the osteoclast, c-fms colony stimulating factor 1 receptor, a transmembrane tyrosine kinase -receptor, leading to secondary messenger activation of tyrosine kinase Src. Both of these molecules are necessary for osteoclastogenesis and are widely involved in the differentiation of monocytemacrophage derived cells.RANKL is a member of the tumour necrosis family TNF, and is essential in osteoclastogenesis. RANKL knockout mice exhibit a phenotype of osteopetrosis and defects of tooth eruption, along with an absence or deficiency of osteoclasts. RANKL activates NF-κβ nuclear factor-κβ and NFATc1 nuclear factor of activated t cells, cytoplasmic, calcineurin-dependent 1 through RANK. NF-κβ activation is stimulated almost immediately after RANKL-RANK interaction occurs, and is not upregulated. NFATc1 stimulation, however, begins 24-48 hours after binding occurs and its expression has been shown to be RANKL dependent.Osteoclast differentiation is inhibited by osteoprotegerin OPG, which binds to RANKL thereby preventing interaction with RANK. 