ONO-1301 Enhances in vitro Osteoblast Differentiation and in vivo Bone Formation Induced by Bone Morphogenetic Protein

Sadaaki Kanayama, Takashi Kaito, Kazuma Kitaguchi, Hiroyuki Ishiguro, Kunihiko Hashimoto, Ryota Chijimatsu, Satoru Otsuru, Shota Takenaka, Takahiro Makino, Yusuke Sakai, Akira Myoui, Hideki Yoshikawa

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)E616-E624
JournalSpine
Volume43
Issue number11
DOIs
Publication statusPublished - Jun 1 2018
Externally publishedYes

Keywords

  • bone formation
  • bone morphogenetic protein
  • bone regeneration
  • micro-computed tomography
  • microsphere
  • muscle pouch transplantation
  • ONO-1301
  • osteoblastic differentiation
  • prostacyclin agonist
  • prostaglandin
  • spinal fusion

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Clinical Neurology

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