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Low dose fibroblast growth factor-2 (FGF-2) enhances bone morphogenetic protein-2 (BMP-2)-induced ectopic bone formation in mice
- Source :
- Bone. 36:399-407
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
Abstract
- To examine how fibroblast growth factor-2 (FGF-2) affects the BMP signaling pathway during bone morphogenetic protein-2 (BMP-2)-induced ectopic bone formation, we implanted type I collagen disks containing constant amounts of BMP-2 (5 micrograms) and varying amounts of FGF-2 onto the back muscles of adult male mice. We then performed histological analyses and histomorphometry, and measured bone mineral density and radiopaque area on the discs 1, 2, and 3 weeks after implantation. We also determined the expression profiles of several genes involved in bone formation and the BMP signaling pathway in the muscle that had been adjacent to the implanted disc and in muscle-derived primary culture cells that had similarly been treated with a constant concentration of BMP-2 and a varying concentration of FGF-2. In the presence of a constant amount of BMP-2, we confirmed that low doses of FGF-2 increased ectopic bone formation in vivo and high doses inhibited bone formation. Northern and/or Western blots of recovered muscle from the in vivo experiment and treated muscle-derived primary culture cells from the in vitro experiment revealed that low doses of FGF-2, but not high doses, increased the expression BMP receptor (BMPR)-1B, phosphorylated Smad1, Noggin, and Osteocalcin. Our results indicate that low-dose FGF-2 may facilitate BMP-2-induced ectopic bone formation by altering the expression of BMPRs on the surface of bone forming progenitor cells. They also indicate that the inhibitory effect of high-dose FGF-2 is not mediated via increased expression of the BMP inhibitor Noggin.
- Subjects :
- Male
medicine.medical_specialty
animal structures
Histology
Physiology
Endocrinology, Diabetes and Metabolism
Basic fibroblast growth factor
Bone Morphogenetic Protein 2
Bone morphogenetic protein
Bone morphogenetic protein 2
Drug Administration Schedule
Mice
chemistry.chemical_compound
Bone Density
Osteogenesis
Transforming Growth Factor beta
Internal medicine
medicine
Animals
Noggin
Muscle, Skeletal
BMP signaling pathway
Bone mineral
biology
Ossification, Heterotopic
Drug Synergism
Bone morphogenetic protein 7
Endocrinology
chemistry
Bone Morphogenetic Proteins
embryonic structures
Osteocalcin
biology.protein
Fibroblast Growth Factor 2
Signal Transduction
Subjects
Details
- ISSN :
- 87563282
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- Bone
- Accession number :
- edsair.doi.dedup.....02b8c55b79ed42c18e592164b25e4379