Molecular Understanding of Osteoclast Differentiation and Physiology

Two types of cells, osteoblasts and osteoclasts, maintain bone homeostasis by balancing each other’s function [1,2]. Osteoblasts, which build bone, are derived from a mesenchymal progenitor cell that can also differentiate into marrow stromal cells and adipocytes [3]. Osteoclasts, originating from hemopoietic progenitors of the monocyte/macrophage lineage, immigrate into bone via the blood stream and resorb mineralized tissues [1,2,4]. Bone through this continuous dynamic remodeling provides structural integrity, skeletal strength, and a reservoir for hematopoiesis. Elevated osteoclast numbers and activity cause osteoporosis, Paget’s disease, tumor osteolysis, various arthritis, and periodontal disease. These diseases result in low bone mass and high fracture risk, which can also occur as a result of an osteoblast defect. To become multinucleated mature osteoclasts, mononuclear precursor cells fuse together under two critical conditions, one of which is to have an ‘optimal density’ of precursor cells [5]. The other is an existence of two kinds of cytokines; macrophage-colony stimulating factor (M-CSF), a survival factor, and receptor activator of NF-κB ligand (RANKL), a differentiation factor [4]. Since spleen cells and stromal cells can secrete M-CSF and RANKL, the combined of bone marrow and these cells can have the same effect compared to their treatment [6]. Here I will provide brief description of osteoclast physiology and focus on the current understanding of the molecules affecting osteoclast differentiation. Enhanced understanding of bone biology will require reviewing the known molecular mechanisms involved in osteoclastogenesis. OSTEOCLAST PHYSIOLOGY