Generating Human Osteoclasts from Peripheral Blood

Osteoclasts are large multinucleated cells that are uniquely specialized for the function of lacunar bone resorption. For much of the previous century osteoclasts were thought to share a common progenitor cell with osteoblasts, bone-forming cells. Osteoclast formation occurring as a consequence of fusion of nonosteoblastic mononuclear precursor cells was suggested by a number of early investigators including Pommer (1883), Mallory (1912), La Coste (1923), and Hancock (1949) (for review see ref. 1 ). It was subsequently established by numerous studies that osteoclasts are derived from a hematopoietic marrow precursor (2 ). These studies included parabiosis experiments in which normal and affected (osteopetrotic/radiation-treated) littermates are linked by a common circulation; these experiments established that the mononuclear osteoclast precursor is present in peripheral blood (3 ,4 ).