Leukotriene B4 loaded in microspheres regulate the expression of genes related to odontoblastic differentiation and biomineralization by dental pulp stem cells

Silva, Francine Lorencetti da; Lamarque, Giuliana de Campos Chaves; Oliveira, Fernanda Maria Machado Pereira Cabral de; Nelson‐Filho, Paulo; Silva, Léa Assed Bezerra da; Faccioli, Lúcia Helena; Paula-Silva, Francisco Wanderley Garcia

doi:10.1186/s12903-022-02083-8

Cited by 4 publications

(2 citation statements)

References 37 publications

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“…Not only the modulation of cell proliferation was affected by lipid inflammatory mediators, but also the expression of important genes inducing dentinal matrix mineralization (76,77). Previously, PGE 2 has already been shown to have an anabolic effect on osteoblast proliferation and differentiation and induced IBSP transcription (78).…”

Section: Involvement Of Lipid Inflammatory Mediators In Biomineraliza...mentioning

confidence: 99%

Effects of inflammation in dental pulp cell differentiation and reparative response

et al. 2022

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The responsiveness of the dentin-pulp complex is possible due to the stimulation of dental pulp cells, which begin to synthesize and secrete dentin matrix. The inflammatory process generated by harmful stimuli should be understood as a natural event of the immune response, resulting in the recruitment of hematopoietic cells, which cross the endothelial barrier and reach the site affected by the injury in order to eliminate the damage and provide an appropriate environment for the restoration of homeostasis. The repair process occurs in the presence of adequate blood supply, absence of infection, and with the participation of pro-inflammatory cytokines, growth factors, extracellular matrix components, and other biologically active molecules. Prostaglandins and leukotrienes are bioactive molecules derived from the metabolism of arachidonic acid, as a result of a variable range of cellular stimuli. The aim of this review is to describe the process of formation and biomineralization of the dentin-pulp complex and how pro-inflammatory events can modify this response, with emphasis on the lipid mediators prostaglandins and leukotrienes derived from arachidonic acid metabolism.

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Section: Involvement Of Lipid Inflammatory Mediators In Biomineraliza...mentioning

confidence: 99%

Effects of inflammation in dental pulp cell differentiation and reparative response

et al. 2022

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“…Due to these advantages, tissue engineering and regenerative medicine have placed a significant amount of attention on hDPSCs [7][8][9]. In these fields, odontoblastic differentiation of hDP-SCs exhibits the capacity of dental pulp regeneration and dentin complex rebuilding [10][11][12]. Nevertheless, the mechanisms under oriented differentiation of hDPSCs are not yet fully understood.…”

Section: Introductionmentioning

confidence: 99%

BACH1 regulates the proliferation and odontoblastic differentiation of human dental pulp stem cells

Liu

et al. 2022

BMC Oral Health

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Background The preservation of biological and physiological vitality as well as the formation of dentin are among the main tasks of human dental pulp for a life time. Odontoblastic differentiation of human dental pulp stem cells (hDPSCs) exhibits the capacity of dental pulp regeneration and dentin complex rebuilding. Exploration of the mechanisms regulating differentiation and proliferation of hDPSCs may help to investigate potential clinical applications. BTB and CNC homology 1 (BACH1) is a transcription repressor engaged in the regulation of multiple cellular functions. This study aimed to investigate the effects of BACH1 on the proliferation and odontoblastic differentiation of hDPSCs in vitro. Methods hDPSCs and pulpal tissues were obtained from extracted human premolars or third molars. The distribution of BACH1 was detected by immunohistochemistry. The mRNA and protein expression of BACH1 were examined by qRT-PCR and Western blot analysis. BACH1 expression was regulated by stable lentivirus-mediated transfection. Cell proliferation and cell cycle were assessed by cell counting kit-8 assay, 5-Ethynyl-2'-deoxyuridine assay and flow cytometry. The expression of mineralization markers, alkaline phosphatase (ALP) activity and alizarin red S staining were conducted to assess the odontoblastic differentiation ability. Results BACH1 expression was stronger in the odontoblast layer than in the cell rich zone. The total and nuclear protein level of BACH1 during odontoblastic differentiation was downregulated initially and then upregulated gradually. Knockdown of BACH1 greatly inhibited cell proliferation, arrested cell cycle, upregulated the heme oxygenase-1 (HO-1) expression and attenuated ALP activity, decreased calcium deposits and downregulated the expression of mineralization markers. Treatment of Tin-protoporphyrin IX, an HO-1 inhibitor, failed to rescue the impaired odonto/osteogenic differentiation capacity. Overexpression of BACH1 increased cell proliferation, ALP activity and the expression of mineralization markers. Conclusions Our findings suggest that BACH1 is an important regulator of the proliferation and odontoblastic differentiation of hDPSCs in vitro. Manipulation of BACH1 expression may provide an opportunity to promote the regenerative capacity of hDPSCs.

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Leukotriene B4 Loaded in Microspheres Inhibits Osteoclast Differentiation and Activation

et al. 2022

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To investigate osteoclast formation in vivo and if leukotriene B4 (LTB4) loaded in microspheres (MS) could be used as a therapeutical strategy to promote a sustained delivery of the mediator and prevent osteoclast differentiation. Methods: In vivo, apical periodontitis was induced in mice to investigate osteoclast differentiation and signaling in absence of 5-lipoxygenase (5-LO). In vitro, LTB4-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process. Characterization and efficiency of LTB4 encapsulation were investigated. J774A.1 macrophages were cultured in the presence of monocyte colony-stimulating factor (M-CSF) and ligand for receptor activator of nuclear factor kappa B (RANKL) and then stimulated with LTB4-MS. Cytotoxicity, in vitro MS-LTB4 uptake, osteoclast formation and gene expression were measured. Results: We found that 5-LO negatively regulates osteoclastic formation in vivo during apical periodontitis development. In vitro, LTB4-MS were up-taken by macrophages and were not cytotoxic to the cells. LTB4-MS inhibited osteoclast formation and the synthesis of osteoclastogenic genes Acp5, Mmp9, Calcr and Ctsk. LTB4-MS inhibited differentiation of macrophages into an osteoclastic phenotype and cell activation under M-CSF and RANKL stimulus.

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Leukotriene B4 loaded in microspheres regulate the expression of genes related to odontoblastic differentiation and biomineralization by dental pulp stem cells

Cited by 4 publications

References 37 publications

Effects of inflammation in dental pulp cell differentiation and reparative response

Effects of inflammation in dental pulp cell differentiation and reparative response

BACH1 regulates the proliferation and odontoblastic differentiation of human dental pulp stem cells

Leukotriene B4 Loaded in Microspheres Inhibits Osteoclast Differentiation and Activation

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