Remodeling of the osteoimmune microenvironment after biomaterials implantation in murine tibia: Single-cell transcriptome analysis

Li, Jia; Zhao, Congrui; Xu, Yangbo; Song, Lu; Chen, Yanqi; Xu, Yuzi; Ma, Yan; Wang, Siyuan; Xu, Antian; He, Fuming

doi:10.1016/j.bioactmat.2022.10.009

Cited by 14 publications

(13 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the last years, the concept of osteoimmunology has been highlighted, and osseointegration seems to be a foreign body reaction (FBR) equilibrium whose mechanism depends on a complex cellular heterogeneity and dynamic changes within the implant-mediated osteoimmune microenvironment. This was demonstrated in a recent study that mapped the general osteoimmune microenvironment around the bone implant through single cell RNA sequencing, scRNA-seq (56). Under this biological context, it has been suggested that primary (early) failure, MBL, and periimplantitis (late loss/failure) are clinical terms that, respectively, describe a picture of early, transitory or late breakdown of osseointegration (57).…”

Section: Stages Of Osseointegration Failurementioning

confidence: 96%

Osteoimmune regulation underlies oral implant osseointegration and its perturbation

et al. 2023

View full text Add to dashboard Cite

In the field of biomaterials, an endosseous implant is now recognized as an osteoimmunomodulatory but not bioinert biomaterial. Scientific advances in bone cell biology and in immunology have revealed a close relationship between the bone and immune systems resulting in a field of science called osteoimmunology. These discoveries have allowed for a novel interpretation of osseointegration as representing an osteoimmune reaction rather than a classic bone healing response, in which the activation state of macrophages ((M1–M2 polarization) appears to play a critical role. Through this viewpoint, the immune system is responsible for isolating the implant biomaterial foreign body by forming bone around the oral implant effectively shielding off the implant from the host bone system, i.e. osseointegration becomes a continuous and dynamic host defense reaction. At the same time, this has led to the proposal of a new model of osseointegration, the foreign body equilibrium (FBE). In addition, as an oral wound, the soft tissues are involved with all their innate immune characteristics. When implant integration is viewed as an osteoimmune reaction, this has implications for how marginal bone is regulated. For example, while bacteria are constitutive components of the soft tissue sulcus, if the inflammatory front and immune reaction is at some distance from the marginal bone, an equilibrium is established. If however, this inflammation approaches the marginal bone, an immune osteoclastic reaction occurs and marginal bone is removed. A number of clinical scenarios can be envisioned whereby the osteoimmune equilibrium is disturbed and marginal bone loss occurs, such as complications of aseptic nature and the synergistic activation of pro-inflammatory pathways (implant/wear debris, DAMPs, and PAMPs). Understanding that an implant is a foreign body and that the host reacts osteoimmunologically to shield off the implant allows for a distinction to be drawn between osteoimmunological conditions and peri-implant bone loss. This review will examine dental implant placement as an osteoimmune reaction and its implications for marginal bone loss.

show abstract

Section: Stages Of Osseointegration Failurementioning

confidence: 96%

Osteoimmune regulation underlies oral implant osseointegration and its perturbation

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Others have used scRNAseq to demonstrate pathologic roles of macrophage subpopulations in acute lung inflammation 34 , and have shown that pharmacologically targeting a subpopulation was beneficial in kidney injury 35 . Regenerative or healing macrophage subpopulations have also been identified via scRNAseq to promote osteointegration around titanium tibia implants 36 and angiogenesis and scar-free healing of skin grafts 37 . To date, there are limited studies that have used scRNAseq to identify macrophage subpopulations in the periodontium and allow the comparisons of these subpopulations across conditions of health, disease, and resolution.…”

Section: Discussionmentioning

confidence: 99%

Single-cell Transcriptional Analysis of the Cellular Immune Response in the Oral Mucosa of Mice

Cantalupo,

Diacou,

Park

et al. 2023

Preprint

View full text Add to dashboard Cite

Periodontal health is dependent on a symbiotic relationship of the host immune response with the oral microbiota. Pathologic shifts of the microbial plaque elicit an immune response that eventually leads to the recruitment and activation of osteoclasts and matrix metalloproteinases and the eventual tissue destruction that is evident in periodontal disease. Once the microbial stimulus is removed, an active process of inflammatory resolution begins. The goal of this work was to use scRNAseq to demonstrate the unique cellular immune response across three distinct conditions of periodontal health, disease, and resolution using mouse models. Periodontal disease was induced using a ligature model. Resolution was modeled by removing the ligature and allowing the mouse to recover. Immune cells (Cd45+) were isolated from the periodontium and analyzed via scRNAseq. Gene signature shifts across the three conditions were characterized and shown to be largely driven by macrophage and neutrophils during the periodontal disease and resolution conditions. Resolution of periodontal disease was characterized by the differential regulation of unique gene subsets. Clustering analysis characterized multiple cellular subpopulations within B Cells, macrophages, and neutrophils that demonstrated differential expansion and contraction across conditions of periodontal health, disease, and resolution. Interestingly, we identified a transcriptionally distinct macrophage subpopulation that expanded during the resolution condition and demonstrated an immunoregulatory gene signature. We identified a cell surface marker for this resolution-associated macrophage subgroup (Cd74) and validated the expansion of this subgroup during resolution via flow cytometry. This work presents a robust immune cell atlas for study of the immunological changes in the oral mucosa during three distinct conditions of periodontal health, disease, and resolution and it improves our understanding of the cellular and molecular markers that characterize health from disease for the development of future diagnostics and therapies.

show abstract

“…Besides, the roles of CDH2 in Sr‐mediated late‐stage osteogenic differentiation and long‐term osseointegration remain unknown, which warrant further attention. Furthermore, despite the fact that models of implant in tibia have been widely used to research implant osseointegration (Alshahrani et al, 2020; Karazisis et al, 2021; Li et al, 2023), they may not faithfully simulate the oral microflora, soft tissue sealing, and chewing stress and strain in oral implant osseointegration. Further studies to investigate the effect and mechanisms on alveolar bones and in humans would be recommended to further establish the result.…”

Section: Limitationsmentioning

confidence: 99%

Strontium‐modified titanium substrate promotes osteogenic differentiation of MSCs and implant osseointegration via upregulating CDH2

Zhou

Song

et al. 2023

Clinical Oral Implants Res

Self Cite

View full text Add to dashboard Cite

show abstract

Remodeling of the osteoimmune microenvironment after biomaterials implantation in murine tibia: Single-cell transcriptome analysis

Cited by 14 publications

References 96 publications

Osteoimmune regulation underlies oral implant osseointegration and its perturbation

Osteoimmune regulation underlies oral implant osseointegration and its perturbation

Single-cell Transcriptional Analysis of the Cellular Immune Response in the Oral Mucosa of Mice

Strontium‐modified titanium substrate promotes osteogenic differentiation of MSCs and implant osseointegration via upregulating CDH2

Contact Info

Product

Resources

About