Dissertation/Thesis Abstract

Matrix-embedded cells control osteoclast formation
by Xiong, Jinhu, Ph.D., University of Arkansas for Medical Sciences, 2012, 172; 3552078
Abstract (Summary)

Osteoclasts resorb the mineralized matrices formed by chondrocytes or osteoblasts. The cytokine receptor activator of nuclear factor-kB ligand (RANKL) is required for osteoclastogenesis and thought to be supplied by osteoblasts or their precursors, thereby linking bone formation to resorption. However, a variety of cell types can express RANKL and the identity of cells that support osteoclastogenesis remains unclear. To elucidate this question, we have deleted the RANKL gene specifically from different cell populations in vivo and demonstrated 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 and hyperparathyroidism. Contrary to the current paradigm, RANKL produced by osteoblasts or their progenitors does not contribute to bone remodeling. These results suggest that the rate-limiting step of matrix resorption is controlled by cells embedded within the matrix itself.

Indexing (document details)
Advisor: O'Brien, Charles A.
Commitee: Jilka, Robert L., Soderberg, Lee S. F, Wight, Patricia A., Zhou, Daohong
School: University of Arkansas for Medical Sciences
Department: Interdisciplinary Biomedical Sciences
School Location: United States -- Arkansas
Source: DAI-B 74/06(E), Dissertation Abstracts International
Subjects: Cellular biology, Endocrinology
Keywords: Bone formation, Matrix-embedded cells, Osteoclasts, Osteocytes, RANKL
Publication Number: 3552078
ISBN: 978-1-267-90306-8
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