Review
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Orthop. Dec 18, 2012; 3(12): 212-222
Published online Dec 18, 2012. doi: 10.5312/wjo.v3.i12.212
Osteoclast fusion and regulation by RANKL-dependent and independent factors
Lianping Xing, Yan Xiu, Brendan F Boyce
Lianping Xing, Yan Xiu, Brendan F Boyce, Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, United States
Author contributions: Xing L and Boyce BF involve in experimental design, data analysis and interpretation, drafting the manuscript and final approval of the version to be published; Xiu Y involves in experimental design, acquisition of data and data analysis, revising the manuscript, and final approval of the version to be published.
Supported by (in part) Grants R01-AR43510 to Boyce BF and R01-AR48697 to Xing L from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, United States
Correspondence to: Lianping Xing, PhD, Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 626, Rochester, NY 14642, United States. lianping_xing@urmc.rochester.edu
Telephone: +1-585-273-4090 Fax: +1-585-756-4468
Received: June 7, 2012
Revised: November 21, 2012
Accepted: December 6, 2012
Published online: December 18, 2012
Abstract

Osteoclasts are the bone resorbing cells essential for bone remodeling. Osteoclasts are formed from hematopoietic progenitors in the monocyte/macrophage lineage. Osteoclastogenesis is composed of several steps including progenitor survival, differentiation to mono-nuclear pre-osteoclasts, fusion to multi-nuclear mature osteoclasts, and activation to bone resorbing osteoclasts. The regulation of osteoclastogenesis has been extensively studied, in which the receptor activator of NF-κB ligand (RANKL)-mediated signaling pathway and downstream transcription factors play essential roles. However, less is known about osteoclast fusion, which is a property of mature osteoclasts and is required for osteoclasts to resorb bone. Several proteins that affect cell fusion have been identified. Among them, dendritic cell-specific transmembrane protein (DC-STAMP) is directly associated to osteoclast fusion in vivo. Cytokines and factors influence osteoclast fusion through regulation of DC-STAMP. Here we review the recently discovered new factors that regulate osteoclast fusion with specific focus on DC-STAMP. A better understanding of the mechanistic basis of osteoclast fusion will lead to the development of a new therapeutic strategy for bone disorders due to elevated osteoclast bone resorption. Cell-cell fusion is essential for a variety of cellular biological processes. In mammals, there is a limited number of cell types that fuse to form multinucleated cells, such as the fusion of myoblasts for the formation of skeletal muscle and the fusion of cells of the monocyte/macrophage lineage for the formation of multinucleated osteoclasts and giant cells. In most cases, cell-cell fusion is beneficial for cells by enhancing function. Myoblast fusion increases myofiber size and diameter and thereby increases contractile strength. Multinucleated osteoclasts have far more bone resorbing activity than their mono-nuclear counterparts. Multinucleated giant cells are much more efficient in the removal of implanted materials and bacteria due to chronic infection than macrophages. Therefore, they are also called foreign-body giant cells. Cell fusion is a complicated process involving cell migration, chemotaxis, cell-cell recognition and attachment, as well as changes into a fusion-competent status. All of these steps are regulated by multiple factors. In this review, we will discuss osteoclast fusion and regulation.

Keywords: Osteoclasts; Fusion; Dendritic cell-specific transmembrane protein; Receptor activator of NF-κB ligand; Bone resorption.