Leptin receptor (+) stromal cells respond to periodontitis and attenuate alveolar bone repair via CCRL2-mediated Wnt inhibition.
J Bone Miner Res
; 39(5): 611-626, 2024 May 24.
Article
em En
| MEDLINE
| ID: mdl-38477792
ABSTRACT
The impaired bone healing in tooth extraction sockets due to periodontitis presents a major obstacle to restoring oral health. The mechanisms regulating the osteogenic capacity of jawbone-derived stromal cells in the periodontitis microenvironment remain elusive. Leptin receptor (LepR) expressing stromal cells, which largely overlap with Cxcl12-abundant reticular (CAR) cells in bone tissue, rapidly proliferate and differentiate into bone-forming cells during extraction socket healing to support alveolar bone repair. In this study, we identify that CCRL2 is significantly expressed and inhibits osteogenesis in LepR+/CAR cells of alveolar bones with periodontitis. The Ccrl2-KO mice exhibit significant improvements in bone healing in extraction sockets with periodontitis. Specifically, the binding of CCRL2 to SFRP1 on the surface of LepR+/CAR cells can amplify the suppressive effect of SFRP1 on Wnt signaling under inflammation, thus hindering the osteogenic differentiation of LepR+/CAR cells and resulting in poor bone healing in extraction sockets with periodontitis. Together, we clarify that the CCRL2 receptor of LepR+/CAR cells can respond to periodontitis and crosstalk with Wnt signaling to deteriorate extraction socket healing.
The impaired bone healing in tooth extraction sockets due to periodontitis presents a major obstacle to restoring oral health. Alterations in the cellular activity of LepR+/CAR cells, an essential stromal cell population for extraction socket healing, in the periodontitis microenvironment have yet to be determined. In this study, we identify that CCRL2, as a potent agent of inflammation-bone crosstalk, is significantly expressed and inhibits osteogenesis in LepR+/CAR cells of alveolar bones with periodontitis. Specifically, the binding of CCRL2 to SFRP1 on the surface of LepR+/CAR cells can amplify the suppressive effect of SFRP1 on the Wnt/ß-catenin signaling under inflammation, thus hindering the osteogenic differentiation of LepR+/CAR cells and resulting in poor bone healing in tooth extraction sockets with periodontitis.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
/
Periodontite
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Receptores para Leptina
/
Receptores CCR
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Via de Sinalização Wnt
Limite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
J Bone Miner Res
Assunto da revista:
METABOLISMO
/
ORTOPEDIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Reino Unido