Caldecrin: A pancreas-derived hypocalcemic factor, regulates osteoclast formation and function

Figure 3 Caldecrin suppresses RANKL-induced osteoclast differentiation and bone resorption. RANKL binds to its receptor (RANK) on the osteoclast precursor, leading to simultaneous activation of two pathways: the NF-κB/ MAPK/c-Fos axis and the Syk/PLCγ-calcium oscillation- NFATc1 axis. In mature osteoclasts, RANKL also activates the NF-κB/MAPK and Src/Syk/Pyk2-TRPV4 channel–calcium entry–actin ring formation axes. Caldecrin inhibits the latter pathways (but not the NF-κB/MAPK pathway) in the precursor and mature osteoclasts. TRPV4: Transient receptor potential vanilloid channel 4; MAPK: Mitogen-activated protein kinase; RANKL: RANK ligand; PLCγ: Phospholipase Cγ; Pyk2: Proline-rich tyrosine kinase 2; NFATc1: Nuclear factor of activated T-cells cytoplasmic 1; NF-κB: Nuclear factor-kappa B; Syk: Spleen tyrosine kinase.