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Journal of Electron Microscopy Advance Access originally published online on December 9, 2005
Journal of Electron Microscopy 2005 54(5):467-477; doi:10.1093/jmicro/dfi066
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© The Author 2005. Published by Oxford University Press on behalf of Japanese Society of Microscopy. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Effects of osteoprotegerin administration on osteoclast differentiation and trabecular bone structure in osteoprotegerin-deficient mice

Hiroko Yamazaki and Takahisa Sasaki*

Department of Oral Histology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

* To whom correspondence should be addressed. E-mail: oralhist{at}dent.showa-u.ac.jp

Osteoprotegerin (OPG)-deficient mice exhibit severe bone loss including the destruction of growth plate cartilage. Using OPG-deficient mice, we attempted to clarify the differentiation and ultrastructure of osteoclasts located on the destroyed growth plate cartilage and trabecular bone matrix in long bones. In (–/–) homozygous OPG knockout mice, adjacent to the growth plate cartilage, the formation of bone trabeculae without a calcified cartilaginous core resulted in an irregular chondrocyte distribution in the growth plate cartilage. At the metaphyseal ossification center, TRAP-positive osteoclasts showed unusual localization on both type-II collagen-positive cartilage and type-I collagen-positive bone matrix. Osteoclasts located on cartilage matrix lacked a typical ruffled border structure, but formed resorption lacunae. During growth plate cartilage destruction, osteoclasts formed ruffled border structures on bone matrix deposited on the remaining cartilage surfaces. These findings suggest that, in OPG (–/–) mice, osteoclast structure differs, depending on the matrix of either cartilage or bone. Then, we examined the effects of OPG administration on the internal trabecular bone structure and osteoclast differentiation in OPG (–/–) mice. OPG administration to OPG (–/–) mice significantly inhibited trabecular bone loss and maintained the internal trabecular bone structure, but did not reduce the osteoclast number on bone trabeculae. For most osteoclasts, OPG administration caused disappearance or reduction of the ruffled border, but induced neither necrotic nor apoptotic damages. These results suggest that OPG administration is an effective means of maintaining the internal structure and volume of trabecular bone in metabolic bone diseases by inhibition of osteoclastic bone resorption.

Keywords     osteoprotegerin-deficient mouse, cartilage resorption, bone resorption, osteoclast, type-I collagen, type-II collagen

Received     15 April 2005, accepted 20 September 2005


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J Electron Microsc (Tokyo)Home page
R. Suzumoto, M. Takami, and T. Sasaki
Differentiation and function of osteoclasts cultured on bone and cartilage
J. Electron Microsc. (Tokyo), December 1, 2005; 54(6): 529 - 540.
[Abstract] [Full Text] [PDF]



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