Leptin receptor (+) stromal cells respond to periodontitis and attenuate alveolar bone repair via CCRL2-mediated Wnt inhibition.

Publisher: Oxford University Press Country of Publication: England NLM ID: 8610640 Publication Model: Print Cited Medium: Internet ISSN: 1523-4681 (Electronic) Linking ISSN: 08840431 NLM ISO Abbreviation: J Bone Miner Res Subsets: MEDLINE

Publication: January 2024- : [Oxford] : Oxford University Press
Original Publication: New York : Mary Ann Liebert, Inc., c1986-

Periodontitis*/metabolism ; Periodontitis*/pathology ; Receptors, Leptin*/metabolism ; Receptors, Leptin*/deficiency ; Receptors, Leptin*/genetics ; Wnt Signaling Pathway* ; Osteogenesis*; Animals ; Mice ; Mice, Knockout ; Stromal Cells/metabolism ; Stromal Cells/pathology ; Male ; Humans ; Alveolar Process/pathology ; Alveolar Process/metabolism ; Wound Healing ; Membrane Proteins/metabolism

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 Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

2018YFE0202200 National Key Research and Development Program Project of China

Keywords: CCRL2; Cxcl12-abundant reticular cells; Wnt signaling; bone healing; leptin receptor; periodontitis
Local Abstract: [plain-language-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.

0 (Receptors, Leptin)
0 (Sfrp1 protein, mouse)
0 (Membrane Proteins)

Date Created: 20240313 Date Completed: 20240524 Latest Revision: 20240524

20240525

10.1093/jbmr/zjae036

38477792