期刊
JOURNAL OF BONE AND MINERAL RESEARCH
卷 30, 期 2, 页码 286-296出版社
WILEY
DOI: 10.1002/jbmr.2322
关键词
SEMAPHORIN; OSTEOPOROSIS; BONE TARGETING; BONE REMODELING
资金
- Program for New Century Excellent Talents in University [NCET-11-0414]
- National Natural Science Foundation of China [81271108, 81120108010]
- Pre-National Basic Research Program of China (973 Plan) [2012CB722404]
Semaphorins have been recently targeted as new molecules directly implicated in the cell-cell communication that occurs between osteoclasts and osteoblasts. Overexpression of certain semaphorins, such as semaphorin4D (sema4D), is found in an osteoporotic phenotype and plays a key role in osteoclast activity by suppressing osteoblast maturation, thus significantly altering the bone modeling cycle. In the present study, we fabricate a site-specific bone-targeting drug-delivery system from polymeric nanoparticles with the incorporation of siRNA interference molecule for sema4D and demonstrate their cellular uptake and intracellular trafficking within osteoclasts, thus preventing the suppression of osteoblast activity. We then demonstrate in an osteoporotic animal model induced by ovariectomy that weekly intravenous injections led to a significantly greater number of active osteoblasts at the bone surface, resulting in higher bone volume in compromised animals. The findings from the present study demonstrate a novel and promising site-specific therapeutic option for the treatment of osteoporosis via interference of the sema4D-plexin cell communication pathway between osteoclasts and osteoblasts. (c) 2014 American Society for Bone and Mineral Research.
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