Anti-C-FMS antibody prevents osteoclast formation and bone resorption in co-culture of osteoblasts and osteoclast precursors in vitro and in ovariectomized mice

Yasuhiko Nara, Hideki Kitaura, Saika Ogawa, Wei Ren Shen, Jiawei Qi, Fumitoshi Ohori, Takahiro Noguchi, Aseel Marahleh, Adya Pramusita, Ria Kinjo, Itaru Mizoguchi

Research output: Contribution to journalArticlepeer-review

Abstract

Osteoporosis morphology is characterized by bone resorption and decreases in micro-architecture parameters. Anti-osteoporosis therapy targets osteoclasts because bone resorption is a unique function of osteoclasts. Anti-c-fms antibodies against the receptor for macrophage colony-stimulating factor (M-CSF) inhibit osteoclast formation and bone resorption in vitro and in vivo. However, the effect of anti-c-fms antibodies on bone resorption in ovariectomized (OVX) mice is unknown. In this study, we evaluated the effect of anti-c-fms antibodies on osteoclast formation and bone resorption in osteoblast–osteoclast precursor co-culture in vitro and in OVX mice. Osteoblast and osteoclast precursor co-cultures treated with anti-c-fms antibodies showed significantly inhibited osteoclast formation, while cultures without anti-c-fms antibody treatment showed osteoclast formation. However, anti-c-fms antibodies did not change the receptor activator of nuclear factor kappa-B ligand (RANKL) or osteoprotegrin (OPG) expression during osteoblast and osteoclast differentiation in vitro. These results indicate that anti-c-fms antibodies directly affected osteoclast formation from osteoclast precursors in co-culture. OVX mice were treated with intraperitoneal injections of anti-c-fms antibody. The trabecular bone structure of the femur was assessed by micro-computer tomography. The anti-c-fms antibody inhibited osteoclast formation and bone loss compared with PBS-treated OVX mice. These results indicate potential for the therapeutic application of anti-c-fms antibodies for postmenopausal osteoporosis.

Original languageEnglish
Article number6120
Pages (from-to)1-16
Number of pages16
JournalInternational journal of molecular sciences
Volume21
Issue number17
DOIs
Publication statusPublished - 2020 Sep 1

Keywords

  • Anti-c-fms antibody
  • M-CSF
  • OVX
  • Osteoclast

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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