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Boning up on Wolff's Law: mechanical regulation of the cells that make and maintain bone.

by Andreas F Zehnder, Arthur G Kristiansen, Joe C Adams, Saumil N Merchant, Michael J McKenna, Sharon G Kujawa, J You, CE E Yellowley, HJ J Donahue, H Yasuda, N Shima, N Nakagawa, K Yamaguchi, M Kinosaki, S Mochizuki, a Tomoyasu, K Yano, M Goto, a Murakami, E Tsuda, T Morinaga, K Higashio, N Udagawa, N Takahashi, T Suda, Y Xu, H YANG, JO QIAO, Jinhu Xiong, Melda Onal, Robert L Jilka, Robert S Weinstein, Stavros C Manolagas, Charles a O'Brien, J Wolff, V T K Version, H K Väänänen, M Horton, Thuy Thanh To, P Eckhard Witten, Joerg Renn, Dipanjan Bhattacharya, Ann Huysseune, Christoph Winkler, S. L. Teitelbaum, H Tanaka, T Mine, H Ogasa, T Taguchi, C T Liang, Orthopaedic Surgery, The Geelong Hospital, E Jimi, M T Gillespie, T John Martin, Natalie a Sims, Jonathan H Gooi, W S Simonet, D.L L Lacey, Colin R C.R R Dunstan, M.J Kelley, M S Chang, R Lüthy, H Q Nguyen, S Wooden, L Bennett, T Boone, G Shimamoto, M DeRose, R Elliott, a Colombero, H.-L L Tan, G Trail, J Sullivan, E Davy, N Bucay, L Renshaw-Gegg, T M Hughes, D Hill, W Pattison, P Campbell, S Sander, G Van, J Tarpley, P Derby, R Lee, W.J J Boyle, Barbara C Silva, John P Bilezikian, Friederike a Schulte, Davide Ruffoni, Floor M Lambers, David Christen, Duncan J Webster, Gisela Kuhn, Ralph Müller, Stefan Scheiner, Peter Pivonka, Christian Hellmich, Liza J Raggatt, Nicola C Partridge, Jan Zimak, David W Smith, Bruce S Gardiner, Gregory R Mundy, M J Pead, R Suswillo, T M Skerry, S Vedi, L E Lanyon, a M Parfitt, Stanley Osher, James a Sethian, Mayumi Okamoto, Takashi Namba, Tomoyasu Shinoda, Takefumi Kondo, Tadashi Watanabe, Yasuhiro Inoue, Kosei Takeuchi, Yukiko Enomoto, Kumiko Ota, Kanako Oda, Yoshino Wada, Ken Sagou, Kanako Saito, Akira Sakakibara, Ayano Kawaguchi, Kazunori Nakajima, Taiji Adachi, Toshihiko Fujimori, Masahiro Ueda, Shigeo Hayashi, Kozo Kaibuchi, Takaki Miyata, Tomoki Nakashima, Hiroshi Takayanagi, Deborah V Novack, Roberta Faccio, Mikihito Hayashi, Takanobu Fukunaga, Kosaku Kurata, Masatsugu Oh-Hora, Jian Q Feng, Lynda F Bonewald, Tatsuhiko Kodama, Anton Wutz, Erwin F Wagner, Josef M Penninger, Rodrigo Moreno, Magnus Borga, Örjan Smedby, Kenneth Moreland, a Mizuno, N Amizuka, K Irie, N Fujise, T Kanno, Y Sato, T Gomibuchi, N Washida, H Ozawa, Chao Liu, Yan Zhao, Wing-Yee Cheung, Ronak Gandhi, Liyun Wang, Lidan You, Vincent Lemaire, Frank L Tobin, Larry D Greller, Carolyn R Cho, Larry J Suva, E Timms, T Burgess, G Elliott, S Scully, H Hsu, N Hawkins, C Capparelli, a Eli, Y.-X Qian, S Kaufman, I Sarosi, V Shalhoub, G Senaldi, J Guo, J Delaney, Jasreen Kular, Jennifer Tickner, Sm Chim, Jiake Xu, Y-Y Y Kong, H Yoshida, S Morony, a J Oliveira-dos-Santos, a Itie, W Khoo, a Wakeham, T W Mak, Melissa L Knothe Tate, Josée R Adamson, Andrea E Tami, Thomas W Bauer, Jenneke Klein-Nulend, Astrid D Bakker, Rommel G Bacabac, Aviral Vatsa, Sheldon Weinbaum, Junichi Kikuta, Masaru Ishii, Naoki Kida, S Khosla, Yoshitaka Kameo, Narumichi Sato, Masaki Hojo, D Holstead Jones, C R Jacobs, B R Davis, Z Zhou, J M Cimbala, Joanna Ilvesaro, Kalervo Va, S J Hollister, N Kikuchi, L C Hofbauer, B L Riggs, Kim Henriksen, Anita V Neutzsky-Wulff, Morten a Karsdal, Reiko Hanada, Toshikatsu Hanada, Verena Sigl, Daniel Schramek, Bastien Guerry, Philip Rooke, Dan Davison, Thomas Dye, K Jambunathan, Nicolas Goaziou, M G Goff, C R Slyfield, S R Kummari, E V Tkachenko, S E Fischer, Y H Yi, M G Jekir, T M Keaveny, C J Hernandez, A Gefen, R Seliktar, Keywords Cancellous, Daniel P Friedman, Matthias Felleisen, E Filvaroff, R Derynck, S C Cowin, Jan-Hung Chen, Craig a Simmons, Beatriz Castaneda, Yohann Simon, Didier Ferbus, Benoit Robert, Julie Chesneau, Christopher Mueller, Ariane Berdal, Frédéric Lézot, E H Burger, Pascal R Buenzli, Junhwan Jeon, Peter T Cummings, Mark L Johnson, Marc Baud'huin, Laurence Duplomb, Stéphane Teletchea, François Lamoureux, Carmen Ruiz-Velasco, Mike Maillasson, Françoise Redini, Marie-Françoise Heymann, Dominique Heymann, Khairul Salleh Basaruddin, Naoki Takano, Yuto Yoshiwara, Takayoshi Nakano, JE Aubin, E Bonnelye, E M Aarden, P J Nijweide show all authors
Bone ()

Abstract

Osteoclasts resorb the mineralized matrices formed by chondrocytes or osteoblasts. The cytokine receptor activator of nuclear factor-κB ligand (RANKL) is essential for osteoclast formation and thought to be supplied by osteoblasts or their precursors, thereby linking bone formation to resorption. However, RANKL is expressed by a variety of cell types, and it is unclear which of them are essential sources for osteoclast formation. Here we have used a mouse strain in which RANKL can be conditionally deleted and a series of Cre-deleter strains to demonstrate that hypertrophic chondrocytes and osteocytes, both of which are embedded in matrix, are essential sources of the RANKL that controls mineralized cartilage resorption and bone remodeling, respectively. Moreover, osteocyte RANKL is responsible for the bone loss associated with unloading. Contrary to the current paradigm, RANKL produced by osteoblasts or their progenitors does not contribute to adult bone remodeling. These results suggest that the rate-limiting step of matrix resorption is controlled by cells embedded within the matrix itself.

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