How do osteoclasts resorb bone?

Bone resorption is needed in many physiological processes of the skeleton. It is an obligatory event during bone growth, tooth eruption and fracture healing. In adult human skeleton physiological remodeling of bone is strictly dependent on bone resorption. Increased bone resorption is an important determinant in a pathophysiology of osteoporosis and many other metabolic bone diseases. Osteoclasts are cells of hematopoietic origin that are responsible for bone resorption. Their differentiation in bone marrow environment is regulated by a number of cytokines and growth factors that affects maturation of monocyte–macrophage lineage. During evolution osteoclasts have developed efficient machinery for degradation of mineralized bone matrix. In active stage they are highly polarized revealing four specific membrane domains. Osteoclasts express and target vacuolar-ATPase to the ruffled border membrane where it pumps protons into resorption lacuna to dissolve hydroxyapatite. Matrix metalloproteinases and cysteine proteinases are important proteolytic enzymes in the degradation of collagenous bone matrix. Recent studies have indicated that bone resorption products are transcytosed from the ruffled border to the functional secretory domain where they are secreted into extracellular medium. New knowledge and specific features of various cellular functions in the osteoclasts have revealed several new targets for drug development. Further molecular characterization of these will finally lead to development of better treatments for osteoporosis and other metabolic bone diseases.