[How is bone formed and resorbed?-- molecular mechanisms of bone formation and resorption]

Bone has developed as a storage of calcium as well as a supporting tissue in vertebrates. Bone is a complex tissue in which resorption and formation take place throughout life. This process is called bone remodeling. Osteotrophic hormones such as 1 alpha,25-dihydroxyvitamin D3[1 alpha,25 (OH) 2D3], parathyroid hormone (PTH) and calcitonin maintain serum calcium homeostasis within a narrow range of 9 to 10 mg/dl by regulating intestinal absorption of calcium and bone remodeling. Bone tissue contains various types of cells, of which bone-forming osteoblasts and bone-resorbing osteoclasts are mainly responsible for bone remodeling. Osteoblasts arise from common progenitors with chondrocytes, myotubes and adipocytes. Recently, four research groups independently identified core-binding protein alpha-1(Cbfa-1) as a key transcription factor for osteoblast differentiation and bone formation, since Cbaf-1 knockout mice completely lacked bone formation due to maturation arrest of osteoblasts. In contrast, multinucleated osteoclasts are primarily responsible for bone resorption. The recent discovery of new members of tumor necroses factor (TNF) receptor-ligand family has indicated the precise mechanism by which osteoblasts/stromal cells regulate osteoclast formation. Osteoblasts/stromal cells express a new member of the TNF ligand family "osteoclast differentiation factor (ODF)" as a membrane-associated factor. Osteoclast progenitors which express ODF receptor(RANK) recognize ODF through cell-to-cell interaction with osteoblasts/stromal cells, then differentiate into osteoclats. Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) is a soluble decoy receptor for ODF. Thus, ODF, RANK and OPG/OCIF are the three key molecules for osteoclast formation. The discovery of Cbfa-1 and ODF may establish a new way to treat several metabolic bone diseases caused by abnormal bone formation and resorption.