Basic Aspects of Osteoclast Differentiation and Function

Osteoclasts are multinucleated cells of the myeloid lineage that are highly specialized for bone resorption through acidification and exocytosis of bone-degrading enzymes into the space between the osteoclast and underlying bone, termed the resorption lacuna. Physiologic osteoclast activity is essential for normal skeletal development and remodeling to repair skeletal microdamage. Osteopetrosis, a collection of monogenic diseases caused by nonfunctional or absent osteoclasts, underscores the importance of adequate osteoclast function for skeletal health. Excessive osteoclastic bone resorption also results in bone disease, including osteoporosis. In this chapter, we provide information on the cellular origin of osteoclasts, discuss the receptors and signaling pathways that drive osteoclast differentiation, and detail the transcriptional machinery required to express the osteoclast program. We detail the cytoskeletal reorganization and formation of a specialized resorption apparatus required for mineral and matrix resorption. Lastly, we discuss the consequences of perturbation of osteoclast formation or function, both in the context of genetic diseases that map to the osteoclast and in the context of pathologic conditions. The goal of this chapter is to provide a detailed overview of osteoclast formation and function that can serve as a reference for clinician’s interested in the role of the osteoclast in osteoporosis.