C‑X‑C receptor 7 agonist acts as a C‑X‑C motif chemokine ligand 12 inhibitor to ameliorate osteoclastogenesis and bone resorption

Alexander Patera Nugraha, Hideki Kitaura, Fumitoshi Ohori, Adya Pramusita, Saika Ogawa, Takahiro Noguchi, Aseel Marahleh, Yasuhiko Nara, Ria Kinjo, Itaru Mizoguchi

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

The C‑X‑C receptor (CXCR) 7 agonist, VUF11207, is a chemical compound that binds specifically to CXCR7, and negatively regulates C‑X‑C motif chemokine ligand 12 (CXCL12) and CXCR4‑induced cellular events. Lipopolysaccharide (LPS) can induce inflammatory cytokines and pathological bone loss. LPS also induces expression of CXCL12, enhancing sensitivity to receptor activator of NF‑κB ligand (RANKL) and tumor necrosis factor‑α (TNF‑α) in vivo. RANKL and TNF‑α induce the differentiation of osteoclasts into osteoclast precursors and bone resorption. The current study was performed to examine the effects of a CXCR7 agonist on osteoclasto‑ genesis and bone resorption induced by LPS in vivo. In addition, the mechanisms underlying these in vivo effects were investigated by in vitro experiments. Eight‑week‑old male C57BL/6J mice were subcutaneously injected over the calvariae with LPS alone or LPS and CXCR7 agonist. After sacrifice, the number of osteoclasts and the bone resorption area were measured. In vitro experiments were performed to investigate the effects of CXCL12 and CXCR7 agonist on osteoclastogenesis induced by RANKL and TNF‑α. Mice injected with LPS and CXCR7 agonist showed significantly reduced osteoclastogenesis and bone resorption compared with mice injected with LPS alone.

Original languageEnglish
Article number78
JournalMolecular Medicine Reports
Volume25
Issue number3
DOIs
Publication statusPublished - 2022 Mar

Keywords

  • C‑X‑C motif chemokine ligand 12
  • C‑X‑C receptor 7 agonist
  • Osteoclast
  • Receptor activator of NF‑κB ligand
  • Tumor necrosis factor‑α

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