The cell biology of osteoclast function

Osteoclasts are multinucleated cells responsible for bone resorption. They have developed an efficient machinery for dissolving crystalline hydroxyapa tite and degrading organic bone matrix rich in collagen fibers. When initia ting bode resorption, osteoclasts become polarized, and three distinct memb rane domains appear: a ruffled border, a sealing zone and a functional secr etory domain. Simultaneously, the cytoskeleton undergoes extensive reorgani sation, During this process, the actin cytoskeleton forms an attachment rin g at the sealing zone, the membrane domain that anchors the resorbing cell to bone matrix. The ruffled border appears inside the sealing zone, and has several characteristics of late endosomal membrane. Extensive vesicle tran sport to the ruffled border delivers hydrochloric acid and proteases to an area between the ruffled border and the bone surface called the resorption lacuna. In this extracellular compartment, crystalline hydroxyapatite is di ssolved by acid, and a mixture of proteases degrades the organic matrix, Th e degradation products of collagen and other matrix components are endocyto sed, transported through the cell and exocytosed through a functional secre tory domain. This transcytotic route allows osteoclasts to remove large amo unts of matrix-degradation products without losing their tight attachment t o underlying bone. It also facilitates further processing of the degradatio n products intracellularly during the passage through the cell.