Distinct Osteogenic Potentials of BMP-2 and FGF-2 in Extramedullary and Medullary Microenvironments
Open Access
- 26 October 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (21), 7967
- https://doi.org/10.3390/ijms21217967
Abstract
Bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2) have been regarded as the major cytokines promoting bone formation, however, several studies have reported unexpected results with failure of bone formation or bone resorption of these growth factors. In this study, BMP-2 and FGF-2 adsorbed into atellocollagen sponges were transplanted into bone defects in the bone marrow-scarce calvaria (extramedullary environment) and bone marrow-abundant femur (medullary environment) for analysis of their in vivo effects not only on osteoblasts, osteoclasts but also on bone marrow cells. The results showed that BMP-2 induced high bone formation in the bone marrow-scarce calvaria, but induced bone resorption in the bone marrow-abundant femurs. On the other hand, FGF-2 showed opposite effects compared to those of BMP-2. Analysis of cellular dynamics revealed numerous osteoblasts and osteoclasts present in the newly-formed bone induced by BMP-2 in calvaria, but none were seen in either control or FGF-2-transplanted groups. On the other hand, in the femur, numerous osteoclasts were observed in the vicinity of the BMP-2 pellet, while a great number of osteoblasts were seen near the FGF-2 pellets or in the control group. Of note, FCM analysis showed that both BMP-2 and FGF-2 administrated in the femur did not significantly affect the hematopoietic cell population, indicating a relatively safe application of the two growth factors. Together, these results indicate that BMP-2 could be suitable for application in extramedullary bone regeneration, whereas FGF-2 could be suitable for application in medullary bone regeneration.This publication has 48 references indexed in Scilit:
- Dynamic visualization of RANKL and Th17-mediated osteoclast functionJCI Insight, 2013
- FGF-2 expands murine hematopoietic stem and progenitor cells via proliferation of stromal cells, c-Kit activation, and CXCL12 down-regulationBlood, 2012
- Endothelial and perivascular cells maintain haematopoietic stem cellsNature, 2012
- The role of FGF-2 and BMP-2 in regulation of gene induction, cell proliferation and mineralization.Journal of Orthopaedic Surgery and Research, 2011
- FGF-2 Stimulates Periodontal RegenerationJournal of Dental Research, 2010
- Fibroblast growth factors: from molecular evolution to roles in development, metabolism and diseaseThe Journal of Biochemistry, 2010
- BMP4 regulates the hematopoietic stem cell nicheBlood, 2009
- Randomized Study Evaluating Recombinant Human Bone Morphogenetic Protein‐2 for Extraction Socket AugmentationThe Journal of Periodontology, 2005
- Long-Term Culture of Human Bone Marrow Stromal Cells in the Presence of Basic Fibroblast Growth FactorGrowth Factors, 1990
- An in vivo model for study of the angiogenic effects of basic fibroblast growth factorBiochemical and Biophysical Research Communications, 1987