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

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

doi:10.3892/mmr.2022.12594

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

Authors:
- Alexander Patera Nugraha
- Hideki Kitaura
- Fumitoshi Ohori
- Adya Pramusita
- Saika Ogawa
- Takahiro Noguchi
- Aseel Marahleh
- Yasuhiko Nara
- Ria Kinjo
- Itaru Mizoguchi
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Affiliations: Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Aoba‑ku, Sendai, Miyagi 980‑8575, Japan
Published online on: January 11, 2022 https://doi.org/10.3892/mmr.2022.12594
Article Number: 78
Copyright: © Nugraha et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 osteoclastogenesis 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. Moreover, the CXCR7 agonist inhibited CXCL12 enhancement of RANKL‑ and TNF‑α‑induced osteoclastogenesis in vitro. Thus, CXCR7 agonist inhibited LPS‑induced osteoclast‑associated cytokines, such as RANKL and TNF‑α, as well as RANKL‑ and TNF‑α‑induced osteoclastogenesis in vitro by modulating CXCL12‑mediated enhancement of osteoclastogenesis. In conclusion, CXCR7 agonist reduced CXCL12‑mediated osteoclastogenesis and bone resorption.

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