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Yongliang Chen, Yuteng Weng, Jie Huang, Qin Li, Bin Sun, Haicheng Wang, Zuolin Wang, Leptin receptor (+) stromal cells respond to periodontitis and attenuate alveolar bone repair via CCRL2-mediated Wnt inhibition, Journal of Bone and Mineral Research, Volume 39, Issue 5, May 2024, Pages 611–626, https://doi.org/10.1093/jbmr/zjae036
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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.
Lay Summary
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/β-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.