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PlexinA2 mediates osteoblast differentiation via regulation of Runx2.
Cited 16 time in
Web of Science
Cited 17 time in Scopus
- Authors
- Issue Date
- 2012-03
- Citation
- JOURNAL OF BONE AND MINERAL RESEARCH Vol.27 No.3, pp. 552-562
- Keywords
- 의약학 ; AXON GUIDANCE MOLECULE ; PLEXINA2 ; OSTEOBLAST DIFFERENTIATION ; RUNX2 ; BMP 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
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