Chemokine Receptor-2 Deficiency Induced Mild Experimental Periapical Lesion in Mice

Overview

Journal J Dent Sci

Date 2025 Jan 28

PMID 39873018

Authors

Qiao Ling

Ai-Jing Wang

Xiao-Yan Wang

Affiliations

Soon will be listed here.

Abstract

Background/purpose: Macrophages are considered to play an important role in the development of chronic apical periodontitis (CAP). However the function of tissue resident macrophages in CAP is unclear. This study aims to investigate the potential role of macrophages of different origins in CAP.

Materials And Methods: Chemokine receptor-2 deficiency (CCR2) mice and C57BL/6N mice (control group, WT mice) were used to induce apical periodontitis. The pulp of mandibular first molars of both sides were exposed to the oral environment. After 0, 7, 21, 28 days of pulp explosion, animals were sacrificed, the mandibular bones were collected and scanned with micro-CT, further processed for HE & IHC Staining to analyze the development of CAP, as well as the expression of surface markers of macrophages.

Results: Both CCR2 and WT mice exhibited CCR2 negative macrophages in normal periapical area, which indicated the presence of tissue resident macrophages. CCR2 deficiency decreased the number of macrophages in periapical lesions, the M1 type macrophages' number as well as osteoclasts around the edge of the lesion decreased compared to wild type. Meanwhile CCR2 deficiency decreased the volume of periapical lesion significantly compared to wild type, but did not inhibite and disappeare the lesion thoroughly.

Conclusion: Monocyte-macrophage system derived macrophages promote the progression of periapical lesions, while tissue resident macrophages in periodontal ligament might also be involved in the progression of periapical lesion.

References

Hong C, Lin S, Wang H, Shun C, Yang C, Lai E . Metformin Reduces Bone Resorption in Apical Periodontitis Through Regulation of Osteoblast and Osteoclast Differentiation. J Endod. 2023; 49(9):1129-1137. DOI: 10.1016/j.joen.2023.07.005. View

Chen X, Dou J, Fu Z, Qiu Y, Zou L, Huang D . Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalis. J Appl Oral Sci. 2022; 30:e20220316. PMC: 9724497. DOI: 10.1590/1678-7757-2022-0316. View

colic M, Gazivoda D, Vucevic D, Vasilijic S, Rudolf R, Lukic A . Proinflammatory and immunoregulatory mechanisms in periapical lesions. Mol Immunol. 2009; 47(1):101-13. DOI: 10.1016/j.molimm.2009.01.011. View

Azuma M, Samuel R, Gomes-Filho J, Dezan-Junior E, Cintra L . The role of IL-6 on apical periodontitis: a systematic review. Int Endod J. 2013; 47(7):615-21. DOI: 10.1111/iej.12196. View

Bajpai G, Bredemeyer A, Li W, Zaitsev K, Koenig A, Lokshina I . Tissue Resident CCR2- and CCR2+ Cardiac Macrophages Differentially Orchestrate Monocyte Recruitment and Fate Specification Following Myocardial Injury. Circ Res. 2018; 124(2):263-278. PMC: 6626616. DOI: 10.1161/CIRCRESAHA.118.314028. View

Mu X, Li Y, Fan G . Tissue-Resident Macrophages in the Control of Infection and Resolution of Inflammation. Shock. 2020; 55(1):14-23. PMC: 8859816. DOI: 10.1097/SHK.0000000000001601. View

Jia D, Chen S, Bai P, Luo C, Liu J, Sun A . Cardiac Resident Macrophage-Derived Legumain Improves Cardiac Repair by Promoting Clearance and Degradation of Apoptotic Cardiomyocytes After Myocardial Infarction. Circulation. 2022; 145(20):1542-1556. DOI: 10.1161/CIRCULATIONAHA.121.057549. View

Blanks A, Pedersen L, Bohmke N, Mihalick V, Franco R . Sex differences in monocyte CCR2 expression and macrophage polarization following acute exercise. Life Sci. 2022; 299:120557. DOI: 10.1016/j.lfs.2022.120557. View

Sierra-Filardi E, Nieto C, Dominguez-Soto A, Barroso R, Sanchez-Mateos P, Puig-Kroger A . CCL2 shapes macrophage polarization by GM-CSF and M-CSF: identification of CCL2/CCR2-dependent gene expression profile. J Immunol. 2014; 192(8):3858-67. DOI: 10.4049/jimmunol.1302821. View

10.

Wang H, Lai E, Yang C, Lin S, Hong C, Yang H . Intracanal Metformin Promotes Healing of Apical Periodontitis via Suppressing Inducible Nitric Oxide Synthase Expression and Monocyte Recruitment. J Endod. 2019; 46(1):65-73. DOI: 10.1016/j.joen.2019.10.001. View

11.

Fan Y, Lyu P, Bi R, Cui C, Xu R, Rosen C . Creating an atlas of the bone microenvironment during oral inflammatory-related bone disease using single-cell profiling. Elife. 2023; 12. PMC: 9925051. DOI: 10.7554/eLife.82537. View

12.

Gschwandtner M, Derler R, Midwood K . More Than Just Attractive: How CCL2 Influences Myeloid Cell Behavior Beyond Chemotaxis. Front Immunol. 2020; 10:2759. PMC: 6923224. DOI: 10.3389/fimmu.2019.02759. View

13.

Goldman E, Reich E, Abramovitz I, Klutstein M . Inducing Apical Periodontitis in Mice. J Vis Exp. 2019; (150). DOI: 10.3791/59521. View

14.

Khan U, Hashimi S, Bakr M, Forwood M, Morrison N . CCL2 and CCR2 are Essential for the Formation of Osteoclasts and Foreign Body Giant Cells. J Cell Biochem. 2015; 117(2):382-9. DOI: 10.1002/jcb.25282. View

15.

Bracks I, Armada L, Goncalves L, Pires F . Distribution of mast cells and macrophages and expression of interleukin-6 in periapical cysts. J Endod. 2013; 40(1):63-8. DOI: 10.1016/j.joen.2013.09.037. View

16.

Nair P . Pathogenesis of apical periodontitis and the causes of endodontic failures. Crit Rev Oral Biol Med. 2004; 15(6):348-81. DOI: 10.1177/154411130401500604. View

17.

Dick S, Wong A, Hamidzada H, Nejat S, Nechanitzky R, Vohra S . Three tissue resident macrophage subsets coexist across organs with conserved origins and life cycles. Sci Immunol. 2022; 7(67):eabf7777. DOI: 10.1126/sciimmunol.abf7777. View

18.

Nobs S, Kopf M . Tissue-resident macrophages: guardians of organ homeostasis. Trends Immunol. 2021; 42(6):495-507. DOI: 10.1016/j.it.2021.04.007. View

19.

Gomes M, Blattner T, Filho M, Grecca F, Hugo F, Fouad A . Can apical periodontitis modify systemic levels of inflammatory markers? A systematic review and meta-analysis. J Endod. 2013; 39(10):1205-17. DOI: 10.1016/j.joen.2013.06.014. View

20.

Dal-Fabbro R, Marques-de-Almeida M, Cosme-Silva L, Ervolino E, Cintra L, Gomes-Filho J . Chronic alcohol consumption increases inflammation and osteoclastogenesis in apical periodontitis. Int Endod J. 2018; 52(3):329-336. DOI: 10.1111/iej.13014. View