The Effects of M1 and M2 Macrophages on Odontogenic Differentiation of Human Dental Pulp Cells

Park, Hee Chul; Quan, Hongxuan; Zhu, Tingting; Kim, Yongjoon; Kim, Bongju; Yang, Hyeong‐Cheol

doi:10.1016/j.joen.2016.11.003

Cited by 29 publications

(22 citation statements)

References 24 publications

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“…Meanwhile, dentin contains unique proteins different from those in bone and other tissue: DSPP and DMP1 involved in the control of dentin mineralization [ 46 ]. The co-culture of human dental pulp cells (DPCs) with M2 conditional medium enhances odontogenic capacities of DPCs, such as increased ALP activity, DSPP expression, and matrix mineralization [ 47 ]. Apart from highly expressed DSPP in regenerated pulp and PDL tissues, the timely recruited M2 phenotypes downregulated expression of MMPs to rescue impaired odontogenesis-related proteins.…”

Section: Discussionmentioning

confidence: 99%

Recruited CD68+CD206+ macrophages orchestrate graft immune tolerance to prompt xenogeneic-dentin matrix-based tooth root regeneration

Sun

Yang

et al. 2021

Bioactive Materials

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Successful regenerative medicine strategies of xenogeneic extracellular matrix need a synergistic balance among inflammation, fibrosis, and remodeling process. Adaptive macrophage subsets have been identified to modulate inflammation and orchestrate the repair of neighboring parenchymal tissues. This study fabricated PPARγ-primed CD68 + CD206 + M2 phenotype (M2γ), and firstly verified their anti-inflammatory and tissue-regenerating roles in xenogeneic bioengineered organ regeneration. Our results showed that Th1-type CD3 + CD8 + T cell response to xenogeneic-dentin matrix-based bioengineered root complex (xeno-complex) was significantly inhibited by M2γ macrophage in vitro . PPARγ activation also timely recruited CD68 + CD206 + tissue macrophage polarization to xeno-complex in vivo . These subsets alleviated proinflammatory cytokines (TNF-α, IFN-γ) at the inflammation site and decreased CD3 + CD8 + T lymphocytes in the periphery system. When translated to an orthotopic nonhuman primate model, PPARγ-primed M2 macrophages immunosuppressed IL-1β, IL-6, TNF-α, MMPs to enable xeno-complex to effectively escape immune-mediated rejection and initiate graft-host synergistic integrity. These collective activities promoted the differentiation of odontoblast-like and periodontal-like cells to guide pulp-dentin and cementum-PDLs-bone regeneration and rescued partially injured odontogenesis such as DSPP and periostin expression. Finally, the regenerated root showed structure-biomechanical and functional equivalency to the native tooth. The timely conversion of M1-to-M2 macrophage mainly orchestrated odontogenesis, fibrogenesis, and osteogenesis, which represents a potential modulator for intact parenchymal-stromal tissue regeneration of targeted organs.

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Section: Discussionmentioning

confidence: 99%

Recruited CD68+CD206+ macrophages orchestrate graft immune tolerance to prompt xenogeneic-dentin matrix-based tooth root regeneration

Sun

Yang

et al. 2021

Bioactive Materials

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“…Lu et al found that neutrophils and macrophages will aggregate at the site of in vivo biomaterial implantations; however, fewer inflammation mediators were witnessed at the same site on the dECM scaffold implantations [5]. Another study also showed that ECM-containing hydrogel can affect innate immunity by changing the M2/M1 ratio of the host response [51]. Therefore, dECM is a good material choice for scaffold manufacturing, since it effectively mimics the structure and organization of the native tissue and reduces implant-induced immune responses; similarly, CS also has a significant effect in enhancing the biocompatibility of the scaffold, as mentioned above.…”

Section: Resultsmentioning

confidence: 99%

3D-Printed Bioactive Calcium Silicate/Poly-ε-Caprolactone Bioscaffolds Modified with Biomimetic Extracellular Matrices for Bone Regeneration

Chiu

Lin

et al. 2019

IJMS

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Currently, clinically available orthopedic implants are extremely biocompatible but they lack specific biological characteristics that allow for further interaction with surrounding tissues. The extracellular matrix (ECM)-coated scaffolds have received considerable interest for bone regeneration due to their ability in upregulating regenerative cellular behaviors. This study delves into the designing and fabrication of three-dimensional (3D)-printed scaffolds that were made out of calcium silicate (CS), polycaprolactone (PCL), and decellularized ECM (dECM) from MG63 cells, generating a promising bone tissue engineering strategy that revolves around the concept of enhancing osteogenesis by creating an osteoinductive microenvironment with osteogenesis-promoting dECM. We cultured MG63 on scaffolds to obtain a dECM-coated CS/PCL scaffold and further studied the biological performance of the dECM hybrid scaffolds. The results indicated that the dECM-coated CS/PCL scaffolds exhibited excellent biocompatibility and effectively enhanced cellular adhesion, proliferation, and differentiation of human Wharton’s Jelly mesenchymal stem cells by increasing the expression of osteogenic-related genes. They also presented anti-inflammatory characteristics by showing a decrease in the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1). Histological analysis of in vivo experiments presented excellent bone regenerative capabilities of the dECM-coated scaffold. Overall, our work presented a promising technique for producing bioscaffolds that can augment bone tissue regeneration in numerous aspects.

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“…In the healing of mineral trioxide aggregatecapped pulp tissue, M2 macrophages transiently accumulate beneath the provisional layer of regeneration, which suggests that M2 macrophages are involved in the healing of pulp tissue (Takei et al 2014). The role of M2 macrophages in pulpal healing was further reported in another study in which M2 macrophages enhanced the odontogenic differentiation of dental pulp stem cells (Park et al 2017b). Therefore, both M1 and M2 macrophages are expected to play a role in the inflammation and regeneration of pulp tissue in damaged teeth, where they may be exposed to dental resin monomers following teeth restoration with resin-based materials.…”

Section: Introductionmentioning

confidence: 82%

“…The role of M2 macrophages in pulpal healing was further reported in another study in which M2 macrophages enhanced the odontogenic differentiation of dental pulp stem cells (Park et al . ). Therefore, both M1 and M2 macrophages are expected to play a role in the inflammation and regeneration of pulp tissue in damaged teeth, where they may be exposed to dental resin monomers following teeth restoration with resin‐based materials.…”

Section: Introductionmentioning

confidence: 97%

Effects of triethylene glycol dimethacrylate and hydroxyethyl methacrylate on macrophage polarization

et al. 2019

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Aim To evaluate the effects of hydrophilic dental resin monomers, triethylene glycol dimethacrylate (TEGDMA) and hydroxyethyl methacrylate (HEMA), on the polarization of a human monocyte cell line (THP‐1). Methodology THP‐1 cells were treated with resin monomers at noncytotoxic concentrations for 48 h and were analysed for CD86 and CD206 expressions using flow cytometry. The cells were stimulated for polarization in the presence of resin monomers (co‐treatment) or after treatment with monomers (pre‐treatment). CD86 and CD206 mRNA in co‐treated cells was evaluated using quantitative real‐time polymerase chain reaction. The release of TNF‐α and TGF‐β by pre‐treated and co‐treated cells was assessed using enzyme‐linked immunosorbent assay. Morphological changes of macrophages during polarization were observed using bright‐field microscopy. One‐way analysis of variance was used for statistical analysis. Results TEGDMA (1 mmol L−1) and HEMA (2 mmol L−1) did not induce CD86 and CD206 expressions in THP‐1 cells but rather inhibited their expressions in the co‐treated cells. The inhibitory effects also appeared at the transcription level. However, the expression of surface markers was not affected by pre‐treatment with resin monomers. The release of TNF‐α and TGF‐β by M1‐ and M2‐stimulated cells, respectively, was suppressed by co‐treatment (P < 0.05). Microscopic studies revealed that co‐treatment with resin monomers suppressed polarization‐associated morphological changes such as cell volume increase. Conclusions TEGDMA and HEMA inhibited macrophage polarization to both M1 and M2 at the transcription level, and the inhibitory effects disappeared upon the removal of resin monomers from the cell culture.

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The Effects of M1 and M2 Macrophages on Odontogenic Differentiation of Human Dental Pulp Cells

Cited by 29 publications

References 24 publications

Recruited CD68+CD206+ macrophages orchestrate graft immune tolerance to prompt xenogeneic-dentin matrix-based tooth root regeneration

Recruited CD68+CD206+ macrophages orchestrate graft immune tolerance to prompt xenogeneic-dentin matrix-based tooth root regeneration

3D-Printed Bioactive Calcium Silicate/Poly-ε-Caprolactone Bioscaffolds Modified with Biomimetic Extracellular Matrices for Bone Regeneration

Effects of triethylene glycol dimethacrylate and hydroxyethyl methacrylate on macrophage polarization

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