Mapping the immune microenvironment for mandibular alveolar bone homeostasis at single-cell resolution

Weimin Lin,Shiwen Zhang,Caojie Liu,Qiwen Li,Bin Shao,Li Zhang,Qian Wang,Yuan Wang,Xiaohan Zhang,Hanwen Li,Yaqian Chen,Xingying Qi,Danting Zhang,Quan Yuan

doi:10.1038/s41413-021-00141-5

Weimin Lin, Shiwen Zhang + Show 12 more

Open Access

https://doi.org/10.1038/s41413-021-00141-5

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Abstract

Alveolar bone is the thickened ridge of jaw bone that supports teeth. It is subject to constant occlusal force and pathogens invasion, and is therefore under active bone remodeling and immunomodulation. Alveolar bone holds a distinct niche from long bone considering their different developmental origin and postnatal remodeling pattern. However, a systematic explanation of alveolar bone at single-cell level is still lacking. Here, we construct a single-cell atlas of mouse mandibular alveolar bone through single-cell RNA sequencing (scRNA-seq). A more active immune microenvironment is identified in alveolar bone, with a higher proportion of mature immune cells than in long bone. Among all immune cell populations, the monocyte/macrophage subpopulation most actively interacts with mesenchymal stem cells (MSCs) subpopulation. Alveolar bone monocytes/macrophages express a higher level of Oncostatin M (Osm) compared to long bone, which promotes osteogenic differentiation and inhibits adipogenic differentiation of MSCs. In summary, our study reveals a unique immune microenvironment of alveolar bone, which may provide a more precise immune-modulatory target for therapeutic treatment of oral diseases.

Highlights

Due to tooth-derived inflammatory response and occlusal stress stimuli, the metabolism and remodeling of alveolar bone are considered to be the most active among the entire skeletal system.[1,2,3,4] Alveolar bones have a different developmental origin and ossification process compared with long bones and other bones.[5]
Characterization of mandibular alveolar bone single-cell atlas The mouse mandibular alveolar bones were dissected for enzymatic digestion and subjected to droplet-based scRNA-seq (Fig. 1a)
We found that the expression of Bmp[2] and Igf[1], Bmpr1a and Mdk were mainly expressed in mesenchymal stem cells (MSCs), while other which was barely detectable in alveolar bone marrow (ABM)-derived monocytes/macroreceptors were widely expressed in various cell types (Fig. 2d)

Summary

Introduction

Due to tooth-derived inflammatory response and occlusal stress stimuli, the metabolism and remodeling of alveolar bone are considered to be the most active among the entire skeletal system.[1,2,3,4] Alveolar bones have a different developmental origin and ossification process compared with long bones and other bones.[5] Craniofacial bone marrow mesenchymal stem cells (MSCs) show higher proliferation rate and osteogenic differentiation potential, but lower chondrogenic and adipogenic differentiation capability.[6,7] Interestingly, alveolar bone is more resistant to bone loss and adipocytes accumulation than long bone in ovariectomized rodents.[8,9] Alveolar bone contacts with the external microenvironment through the periodontal barrier, which exerts important regulatory effects on immune homeostasis of alveolar bone.[10] accumulating evidence demonstrated unique physiological characteristics of alveolar bone, there is a lack of systematic description of alveolar bone cell heterogeneity and the difference from long bone

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Conclusion