Bone resorption and the relationship between osteoblasts and osteoclasts.  
RANK is expressed on the osteoclasts, allowing signals from other cell types to affect their life cycle and activity. RANKL is expressed on marrow cells and osteoblasts. The binding of RANKL to RANK stimulates osteoclast formation, differentiation, and activation. Villous projections from an osteoclast form a ruffled border on the surface of bone, which increases the membrane surface area. Podosomes and their associated linking proteins (e.g. osteopontin, meaning “bone bridge”) create an adhesive ring around the ruffled border.  This creates a resorptive pit that is sealed off from the adjacent bone and from the ECF, wherein reactions that facilitate resorption occur. Several acids (e.g. citric acid, lactic acid) are released from the mitochondria and secretory vesicles. Hydrogen ions are also released through the actions of carbonic anhydrase and vacuolar ATPase proton pumps.  This creates an acidic environment in the resorptive pit, which results in bone salt dissolution. Proteolytic enzymes (e.g. cathepsin K) are released from lysosomes in the osteoclast. These enzymes break-down the collagen bone matrix and are most active in an acidic environment. Materials within the resorptive pit are phagocytosed and moved across the cell and released into the ECF, this results in an increase in ion concentration in the blood. CaK = cathepsin K, CA = carbonic anhydrase. RANK = receptor activator for nuclear factor κB, RANKL = RANK ligand. 


#Pathophysiology #Endocrinology #Osteoblasts #Osteoclasts #Bone #Resorption #RANKL