TY - JOUR
T1 - C‑X‑C receptor 7 agonist acts as a C‑X‑C motif chemokine ligand 12 inhibitor to ameliorate osteoclastogenesis and bone resorption
AU - Nugraha, Alexander Patera
AU - Kitaura, Hideki
AU - Ohori, Fumitoshi
AU - Pramusita, Adya
AU - Ogawa, Saika
AU - Noguchi, Takahiro
AU - Marahleh, Aseel
AU - Nara, Yasuhiko
AU - Kinjo, Ria
AU - Mizoguchi, Itaru
N1 - Publisher Copyright:
© 2022 Spandidos Publications. All rights reserved.
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
KW - C‑X‑C motif chemokine ligand 12
KW - C‑X‑C receptor 7 agonist
KW - Osteoclast
KW - Receptor activator of NF‑κB ligand
KW - Tumor necrosis factor‑α
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U2 - 10.3892/mmr.2022.12594
DO - 10.3892/mmr.2022.12594
M3 - Article
C2 - 35014674
AN - SCOPUS:85123353613
SN - 1791-2997
VL - 25
JO - Molecular Medicine Reports
JF - Molecular Medicine Reports
IS - 3
M1 - 78
ER -