TY - JOUR
T1 - Distinct osteogenic potentials of BMP-2 and FGF-2 in extramedullary and medullary microenvironments
AU - Nosho, Shuji
AU - Tosa, Ikue
AU - Ono, Mitsuaki
AU - Hara, Emilio Satoshi
AU - Ishibashi, Kei
AU - Mikai, Akihiro
AU - Tanaka, Yukie
AU - Kimura-Ono, Aya
AU - Komori, Taishi
AU - Maekawa, Kenji
AU - Kuboki, Takuo
AU - Oohashi, Toshitaka
N1 - Funding Information:
Acknowledgments: We are grateful to Koichi Matsuo (Keio University, Tokyo, Japan) and Masaru Ishii and Junichi Kikuta (Osaka University, Osaka, Japan) for kindly giving us the Col1a1(2.3)-GFP mice and Trap-tdTomato mice, respectively. We also thank Jochi Shiro and Hiroyuki Irie (Osteopharma Inc. Osaka, Japan) for kindly providing the BMP-2. This work was supported by Central Research Laboratory of Okayama University Medical School (Okayama, Japan).
Funding Information:
Funding: This research was founded by JSPS KAKENHI Grant Numbers JP19H03842, JP18H02991 and JP20K23108.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
KW - BMP-2
KW - Bone formation
KW - Bone marrow
KW - FGF-2
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U2 - 10.3390/ijms21217967
DO - 10.3390/ijms21217967
M3 - Article
C2 - 33120952
AN - SCOPUS:85095398911
SN - 1661-6596
VL - 21
SP - 1
EP - 14
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 21
M1 - 7967
ER -