TY - JOUR
T1 - ONO-1301 Enhances in vitro Osteoblast Differentiation and in vivo Bone Formation Induced by Bone Morphogenetic Protein
AU - Kanayama, Sadaaki
AU - Kaito, Takashi
AU - Kitaguchi, Kazuma
AU - Ishiguro, Hiroyuki
AU - Hashimoto, Kunihiko
AU - Chijimatsu, Ryota
AU - Otsuru, Satoru
AU - Takenaka, Shota
AU - Makino, Takahiro
AU - Sakai, Yusuke
AU - Myoui, Akira
AU - Yoshikawa, Hideki
N1 - Publisher Copyright:
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Study Design. In vitro and in vivo assessment of osteogenic effect by prostacyclin agonist (ONO-1301). Objective. The aim of this study was to investigate the effects of ONO-1301 on in vitro osteoblastic differentiation and in vivo bone formation induced by bone morphogenetic protein (BMP). Summary of Background Data. Among prostaglandins (PGs), PGE 2 is the most abundant in bone tissue and its effects on bone formation have been well studied. PGI 2 (prostacyclin) is the second most abundant PG in bone tissue and plays important roles in hemodynamics. However, the effects of PGI 2 on osteoblast differentiation and bone regeneration have not been elucidated. Methods. The effects of PGI 2 agonist (ONO-1301), with and without recombinant human (rh) BMP-2, on osteoblastic differentiation and cell proliferation were investigated in vitro using alkaline phosphatase (ALP) and WST-1 assays. Murine primary osteoblasts and cell lines (ST2, MC3T3-E1, C2C12, and CH310T1/2) were used for the study. The effects of ONO-1301 on rhBMP-2 induced bone formation were investigated in a mouse model of muscle pouch transplantation (ectopic model) and in a rat model of spinal fusion (orthotopic model). Results. ONO-1301 significantly increased ALP activity in the primary osteoblasts and ST2 cells. In addition, cotreatment with ONO-1301 and rhBMP-2 significantly increased ALP activity in the primary osteoblasts, as well as in ST2 and MC3T3-E1 cells. Cell proliferation was not affected by both ONO-1301 and ONO-1301 as well as rhBMP-2. In the ectopic model, ONO-1301 significantly increased the volume of ectopic bone whose formation was induced by BMP. In addition, in the orthotopic model, ONO-1301 significantly increased bone volume and fusion rate. Conclusion. This study has demonstrated that the PG IP agonist ONO-1301 improves in vitro BMP-2 induced osteoblast differentiation and in vivo ectopic and orthotopic bone formation. The results suggest that ONO-1301 has a potential clinical application as an enhancer of BMP-induced bone formation. Level of Evidence: N/A.
AB - Study Design. In vitro and in vivo assessment of osteogenic effect by prostacyclin agonist (ONO-1301). Objective. The aim of this study was to investigate the effects of ONO-1301 on in vitro osteoblastic differentiation and in vivo bone formation induced by bone morphogenetic protein (BMP). Summary of Background Data. Among prostaglandins (PGs), PGE 2 is the most abundant in bone tissue and its effects on bone formation have been well studied. PGI 2 (prostacyclin) is the second most abundant PG in bone tissue and plays important roles in hemodynamics. However, the effects of PGI 2 on osteoblast differentiation and bone regeneration have not been elucidated. Methods. The effects of PGI 2 agonist (ONO-1301), with and without recombinant human (rh) BMP-2, on osteoblastic differentiation and cell proliferation were investigated in vitro using alkaline phosphatase (ALP) and WST-1 assays. Murine primary osteoblasts and cell lines (ST2, MC3T3-E1, C2C12, and CH310T1/2) were used for the study. The effects of ONO-1301 on rhBMP-2 induced bone formation were investigated in a mouse model of muscle pouch transplantation (ectopic model) and in a rat model of spinal fusion (orthotopic model). Results. ONO-1301 significantly increased ALP activity in the primary osteoblasts and ST2 cells. In addition, cotreatment with ONO-1301 and rhBMP-2 significantly increased ALP activity in the primary osteoblasts, as well as in ST2 and MC3T3-E1 cells. Cell proliferation was not affected by both ONO-1301 and ONO-1301 as well as rhBMP-2. In the ectopic model, ONO-1301 significantly increased the volume of ectopic bone whose formation was induced by BMP. In addition, in the orthotopic model, ONO-1301 significantly increased bone volume and fusion rate. Conclusion. This study has demonstrated that the PG IP agonist ONO-1301 improves in vitro BMP-2 induced osteoblast differentiation and in vivo ectopic and orthotopic bone formation. The results suggest that ONO-1301 has a potential clinical application as an enhancer of BMP-induced bone formation. Level of Evidence: N/A.
KW - bone formation
KW - bone morphogenetic protein
KW - bone regeneration
KW - micro-computed tomography
KW - microsphere
KW - muscle pouch transplantation
KW - ONO-1301
KW - osteoblastic differentiation
KW - prostacyclin agonist
KW - prostaglandin
KW - spinal fusion
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U2 - 10.1097/BRS.0000000000002439
DO - 10.1097/BRS.0000000000002439
M3 - Article
C2 - 29016438
AN - SCOPUS:85048127549
SN - 0362-2436
VL - 43
SP - E616-E624
JO - Spine
JF - Spine
IS - 11
ER -