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Science 1 September 2000:
Vol. 289. no. 5484, pp. 1504 - 1508
DOI: 10.1126/science.289.5484.1504
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Review

Bone Resorption by Osteoclasts

Steven L. Teitelbaum

Osteoporosis, a disease endemic in Western society, typically reflects an imbalance in skeletal turnover so that bone resorption exceeds bone formation. Bone resorption is the unique function of the osteoclast, and anti-osteoporosis therapy to date has targeted this cell. The osteoclast is a specialized macrophage polykaryon whose differentiation is principally regulated by macrophage colony-stimulating factor, RANK ligand, and osteoprotegerin. Reflecting integrin-mediated signals, the osteoclast develops a specialized cytoskeleton that permits it to establish an isolated microenvironment between itself and bone, wherein matrix degradation occurs by a process involving proton transport. Osteopetrotic mutants have provided a wealth of information about the genes that regulate the differentiation of osteoclasts and their capacity to resorb bone.

Department of Pathology, Washington University School of Medicine, Barnes-Jewish Hospital North, Mailstop 90-31-649, 216 South Kingshighway, St. Louis, MO 63110, USA. E-mail: teitelbs{at}medicine.wustl.edu

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Inhibition of Hormone and Cytokine-stimulated Osteoclastogenesis and Bone Resorption by Interleukin-4 and Interleukin-13 Is Associated with Increased Osteoprotegerin and Decreased RANKL and RANK in a STAT6-dependent Pathway.
P. Palmqvist, P. Lundberg, E. Persson, A. Johansson, I. Lundgren, A. Lie, H. H. Conaway, and U. H. Lerner (2006)
J. Biol. Chem. 281, 2414-2429
   Abstract »    Full Text »    PDF »
Guggulsterone Inhibits Osteoclastogenesis Induced by Receptor Activator of Nuclear Factor-{kappa}B Ligand and by Tumor Cells by Suppressing Nuclear Factor-{kappa}B Activation.
H. Ichikawa and B. B. Aggarwal (2006)
Clin. Cancer Res. 12, 662-668
   Abstract »    Full Text »    PDF »
Bone Biology and the Clinical Implications for Osteoporosis.
P. A Downey and M. I Siegel (2006)
Physical Therapy 86, 77-91
   Abstract »    Full Text »    PDF »
Receptor Activator of NF-{kappa}B (RANK) Cytoplasmic Motif, 369PFQEP373, Plays a Predominant Role in Osteoclast Survival in Part by Activating Akt/PKB and Its Downstream Effector AFX/FOXO4.
W. Liu, S. Wang, S. Wei, L. Sun, and X. Feng (2005)
J. Biol. Chem. 280, 43064-43072
   Abstract »    Full Text »    PDF »
Osteoclastogenic Activity during Mandibular Distraction Osteogenesis.
L.C. Wang, I. Takahashi, Y. Sasano, J. Sugawara, and H. Mitani (2005)
Journal of Dental Research 84, 1010-1015
   Abstract »    Full Text »    PDF »
Cells of the Osteoclast Lineage as Mediators of the Anabolic Actions of Parathyroid Hormone in Bone.
A. J. Koh, B. Demiralp, K. G. Neiva, J. Hooten, R. M. Nohutcu, H. Shim, N. S. Datta, R. S. Taichman, and L. K. McCauley (2005)
Endocrinology 146, 4584-4596
   Abstract »    Full Text »    PDF »
Nuclear Factor of Activated T Cells c1 Induces Osteoclast-associated Receptor Gene Expression during Tumor Necrosis Factor-related Activation-induced Cytokine-mediated Osteoclastogenesis.
K. Kim, J. H. Kim, J. Lee, H.-M. Jin, S.-H. Lee, D. E. Fisher, H. Kook, K. K. Kim, Y. Choi, and N. Kim (2005)
J. Biol. Chem. 280, 35209-35216
   Abstract »    Full Text »    PDF »
Transforming Growth Factor-{beta}1 to the Bone.
K. Janssens, P. ten Dijke, S. Janssens, and W. Van Hul (2005)
Endocr. Rev. 26, 743-774
   Abstract »    Full Text »    PDF »
Biominerals.
H. C. W. Skinner (2005)
Mineralogical Magazine 69, 621-641
   Abstract »    Full Text »    PDF »
Physical and Functional Association of c-Src and Adhesion and Degranulation Promoting Adaptor Protein (ADAP) in Osteoclastogenesis in Vitro.
S. Koga, K. Yogo, K. Yoshikawa, H. Samori, M. Goto, T. Uchida, N. Ishida, and T. Takeya (2005)
J. Biol. Chem. 280, 31564-31571
   Abstract »    Full Text »    PDF »
Osthole-Mediated Cell Differentiation through Bone Morphogenetic Protein-2/p38 and Extracellular Signal-Regulated Kinase 1/2 Pathway in Human Osteoblast Cells.
P.-L. Kuo, Y.-L. Hsu, C.-H. Chang, and J.-K. Chang (2005)
J. Pharmacol. Exp. Ther. 314, 1290-1299
   Abstract »    Full Text »    PDF »
{micro}-Calpain Regulates Receptor Activator of NF-{kappa}B Ligand (RANKL)-supported Osteoclastogenesis via NF-{kappa}B Activation in RAW 264.7 Cells.
F. Y.-I. Lee, D.-W. Kim, J. A. Karmin, D. Hong, S.-S. Chang, M. Fujisawa, H. Takayanagi, L. U. Bigliani, T. A. Blaine, and H.-J. Lee (2005)
J. Biol. Chem. 280, 29929-29936
   Abstract »    Full Text »    PDF »
Bisphosphonates in Orthopaedic Surgery.
C. D. Morris and T. A. Einhorn (2005)
J. Bone Joint Surg. Am. 87, 1609-1618
   Abstract »    Full Text »    PDF »
Homeostatic Role of Interferons Conferred by Inhibition of IL-1-Mediated Inflammation and Tissue Destruction.
X. Hu, H. H. Ho, O. Lou, C. Hidaka, and L. B. Ivashkiv (2005)
J. Immunol. 175, 131-138
   Abstract »    Full Text »    PDF »
Rab3D Regulates a Novel Vesicular Trafficking Pathway That Is Required for Osteoclastic Bone Resorption.
N. J. Pavlos, J. Xu, D. Riedel, J. S. G. Yeoh, S. L. Teitelbaum, J. M. Papadimitriou, R. Jahn, F. P. Ross, and M. H. Zheng (2005)
Mol. Cell. Biol. 25, 5253-5269
   Abstract »    Full Text »    PDF »
Potassium Channel-blockers as Therapeutic Agents to Interfere with Bone Resorption of Periodontal Disease.
P. Valverde, T. Kawai, and M.A. Taubman (2005)
Journal of Dental Research 84, 488-499
   Abstract »    Full Text »    PDF »
Evolution and modulation of age-related medial elastocalcinosis: Impact on large artery stiffness and isolated systolic hypertension.
H. H. Dao, R. Essalihi, C. Bouvet, and P. Moreau (2005)
Cardiovasc Res 66, 307-317
   Abstract »    Full Text »    PDF »
Reactive Oxygen Species Stimulates Receptor Activator of NF-{kappa}B Ligand Expression in Osteoblast.
X.-c. Bai, D. Lu, A.-l. Liu, Z.-m. Zhang, X.-m. Li, Z.-p. Zou, W.-s. Zeng, B.-l. Cheng, and S.-q. Luo (2005)
J. Biol. Chem. 280, 17497-17506
   Abstract »    Full Text »    PDF »
Osteoporosis and Integrins.
S. L. Teitelbaum (2005)
J. Clin. Endocrinol. Metab. 90, 2466-2468
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