Boning up on Wolff's Law: mechanical regulation of the cells that make and maintain bone.
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.
Jan Hung Chen, Chao Liu, Lidan You, Craig A. Simmons in Journal of Biomechanics (2010)Save reference to library 98 readers
A Chamay, P Tschantz in Journal of biomechanics (1972)Save reference to library 27 readers
Osbjorn M. Pearson, Daniel E. Lieberman in Yearbook of Physical Anthropology (2004)Save reference to library 199 readers
Wendy E. Thomas, Dennis E. Discher, V. Prasad Shastri in MRS Bulletin (2010)Save reference to library 19 readers
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