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Modulation of Osteoclast Differentiation and Function by the New Members of the Tumor Necrosis Factor Receptor and Ligand Families

Department of Biochemistry (T.S., N.T., N.U., E.J.), School of Dentistry, Showa University, Shinagawa-ku, Tokyo 142-8555, Japan; and St. Vincent’s Institute of Medical Research (M.T.G., T.J.M.), University of Melbourne, Fitzroy, Victoria 3065, Australia

I. Introduction

II. Role of Osteoblasts/Stromal Cells in Osteoclast Differentiation and Function

A. Origin of osteoclasts

B. Stimulation of osteoclast differentiation by osteoblasts/stromal cells

C. Stimulation of osteoclast function by osteoblasts/stromal cells

III. New Members of the Tumor Necrosis Factor (TNF) Receptor and Ligand Families

A. Osteoprotegerin (OPG)

B. Osteoclast differentiation factor (ODF) and stromal osteoclast-forming activity (SOFA)

IV. Regulatory Mechanism in Osteoclast Development and Function

A. Regulatory mechanism of osteoclast differentiation by RANKL

B. Regulatory mechanism of RANKL action on osteoclast function

C. Signals induced by interleukin-1 (IL-1) and RANKL in osteoclasts

V. Regulation of Human Osteoclast Development

VI. Summary and Conclusion