PMID- 35014674
OWN - NLM
STAT- MEDLINE
DCOM- 20220328
LR  - 20220328
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 25
IP  - 3
DP  - 2022 Mar
TI  - C‑X‑C receptor 7 agonist acts as a C‑X‑C motif chemokine ligand 12 inhibitor to 
      ameliorate osteoclastogenesis and bone resorption.
LID - 78 [pii]
LID - 10.3892/mmr.2022.12594 [doi]
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‑kappaB ligand (RANKL) and 
      tumor necrosis factor‑alpha (TNF‑alpha) in vivo. RANKL and TNF‑alpha 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‑alpha. 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‑alpha‑induced osteoclastogenesis in vitro. Thus, 
      CXCR7 agonist inhibited LPS‑induced osteoclast‑associated cytokines, such as 
      RANKL and TNF‑alpha, as well as RANKL‑ and TNF‑alpha‑induced osteoclastogenesis in vitro 
      by modulating CXCL12‑mediated enhancement of osteoclastogenesis. In conclusion, 
      CXCR7 agonist reduced CXCL12‑mediated osteoclastogenesis and bone resorption.
FAU - Nugraha, Alexander Patera
AU  - Nugraha AP
AD  - Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate 
      School of Dentistry, Aoba‑ku, Sendai, Miyagi 980‑8575, Japan.
FAU - Kitaura, Hideki
AU  - Kitaura H
AD  - Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate 
      School of Dentistry, Aoba‑ku, Sendai, Miyagi 980‑8575, Japan.
FAU - Ohori, Fumitoshi
AU  - Ohori F
AD  - Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate 
      School of Dentistry, Aoba‑ku, Sendai, Miyagi 980‑8575, Japan.
FAU - Pramusita, Adya
AU  - Pramusita A
AD  - Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate 
      School of Dentistry, Aoba‑ku, Sendai, Miyagi 980‑8575, Japan.
FAU - Ogawa, Saika
AU  - Ogawa S
AD  - Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate 
      School of Dentistry, Aoba‑ku, Sendai, Miyagi 980‑8575, Japan.
FAU - Noguchi, Takahiro
AU  - Noguchi T
AD  - Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate 
      School of Dentistry, Aoba‑ku, Sendai, Miyagi 980‑8575, Japan.
FAU - Marahleh, Aseel
AU  - Marahleh A
AD  - Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate 
      School of Dentistry, Aoba‑ku, Sendai, Miyagi 980‑8575, Japan.
FAU - Nara, Yasuhiko
AU  - Nara Y
AD  - Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate 
      School of Dentistry, Aoba‑ku, Sendai, Miyagi 980‑8575, Japan.
FAU - Kinjo, Ria
AU  - Kinjo R
AD  - Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate 
      School of Dentistry, Aoba‑ku, Sendai, Miyagi 980‑8575, Japan.
FAU - Mizoguchi, Itaru
AU  - Mizoguchi I
AD  - Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate 
      School of Dentistry, Aoba‑ku, Sendai, Miyagi 980‑8575, Japan.
LA  - eng
PT  - Journal Article
DEP - 20220111
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Biomarkers)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cmkor1 protein, mouse)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RANK Ligand)
RN  - 0 (Receptors, CXCR)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Biomarkers
MH  - Bone Resorption/diagnosis/drug therapy/etiology/*metabolism
MH  - Cells, Cultured
MH  - Chemokine CXCL12/*antagonists & inhibitors
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Lipopolysaccharides/immunology
MH  - Male
MH  - Mice
MH  - Mitogen-Activated Protein Kinases
MH  - Osteogenesis/*drug effects
MH  - Phosphorylation
MH  - RANK Ligand/metabolism
MH  - Receptors, CXCR/*antagonists & inhibitors
MH  - X-Ray Microtomography
PMC - PMC8778739
OTO - NOTNLM
OT  - C‑X‑C motif chemokine ligand 12
OT  - C‑X‑C receptor 7 agonist
OT  - osteoclast
OT  - receptor activator of NF‑kappaB ligand
OT  - tumor necrosis factor‑alpha
COIS- The authors declare that they have no competing interests.
EDAT- 2022/01/12 06:00
MHDA- 2022/03/29 06:00
PMCR- 2022/01/11
CRDT- 2022/01/11 08:48
PHST- 2021/09/06 00:00 [received]
PHST- 2021/12/09 00:00 [accepted]
PHST- 2022/01/11 08:48 [entrez]
PHST- 2022/01/12 06:00 [pubmed]
PHST- 2022/03/29 06:00 [medline]
PHST- 2022/01/11 00:00 [pmc-release]
AID - 78 [pii]
AID - MMR-25-03-12594 [pii]
AID - 10.3892/mmr.2022.12594 [doi]
PST - ppublish
SO  - Mol Med Rep. 2022 Mar;25(3):78. doi: 10.3892/mmr.2022.12594. Epub 2022 Jan 11.