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PlexinA2 mediates osteoblast differentiation via regulation of Runx2.

Cited 14 time in Web of Science Cited 15 time in Scopus
Issue Date
2012-03
Publisher
American Society for Bone and Mineral Research
Citation
JOURNAL OF BONE AND MINERAL RESEARCH Vol.27 No.3, pp. 552-562
Keywords
의약학AXON GUIDANCE MOLECULEPLEXINA2OSTEOBLAST DIFFERENTIATIONRUNX2BMP SIGNALING
Abstract
The imbalance between bone-resorbing osteoclasts and bone-forming osteoblasts often leads to bone destructive diseases such as
osteoporosis. In contrast to the development of several antiresorptive agents for osteoporosis therapy, discovery of anabolic drugs has
been difficult because of an insufficient understanding of the complex mechanism of bone formation. In a microarray analysis with
mouse preosteoblast cells, we found that PlexinA2 (PlxnA2), a molecule previously known to mediate axon guidance in neural
development, was upregulated by the osteogenic factor BMP2. PlxnA2-specific siRNA decreased Runx2 expression, osteoblast
differentiation, and mineralization. Runx2 overexpression restored osteoblastic differentiation of PlxnA2-knockdown cells. PlxnA2
was associated with both type 1 and 2 BMP receptors, and BMP2 increased the interaction between PlxnA2 and type 1 receptors. PlxnA2
also affected Smad and Akt signaling pathways downstream of BMP2. Taken together, the results of our study reveal that PlxnA2 has a
pro-osteogenic function by modulating BMP2 signaling. Therefore, PlxnA2 may be a useful target for development of bone anabolic
therapeutics.
ISSN
0884-0431
Language
English
URI
https://hdl.handle.net/10371/82235
DOI
https://doi.org/10.1002/jbmr.1471
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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