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Regulation of Osteoblast Differentiation Mediated by Bone Morphogenetic Proteins, Hedgehogs, and Cbfa1

Department of Oral Pathology (A.Y.), Nagasaki University School of Dentistry, 1–7-1 Sakamoto, Nagasaki 852, Department of Molecular Medicine (T.K.), School of Medicine, Osaka University, 2–2 Yamada-oka, Suita, Osaka 565 and "Form and Function", PRESTO, Japan Science and Technology Corporation, and Department of Biochemistry (T.S.), School of Dentistry, Showa University, 1–5-8 Hatanodai, Shinagawa-ku, Tokyo 142, Japan

Osteoblasts arise from common progenitors with chondrocytes, muscle and adipocytes, and various hormones and local factors regulate their differentiation. We review here regulation of osteoblast differentiation mediated by the local factors such as bone morphogenetic proteins (BMPs) and hedgehogs and the transcription factor, core-binding factor -1 (Cbfa1). BMPs are the most potent regulators of osteoblast differentiation among the local factors. Sonic and Indian hedgehogs are involved in osteoblast differentiation by interacting with BMPs. Cbfa1, a member of the runt domain gene family, plays a major role in the processes of a determination of osteoblast cell lineage and maturation of osteoblasts. Cbfa1 is an essential transcription factor for osteoblast differentiation and bone formation, because Cbfa1-deficient mice completely lacked bone formation due to maturation arrest of osteoblasts. Although the regulatory mechanism of Cbfa1 expression has not been fully clarified, BMPs are an important local factor that up-regulates Cbfa1 expression. Thus, the intimate interaction between local factors such as BMPs and hedgehogs and the transcription factor, Cbfa1, is important to osteoblast differentiation and bone formation.