Role of myofibroblasts in normal and pathological periodontal wound healing

Ph, Smith

doi:10.1111/odi.12773

Cited by 9 publications

(6 citation statements)

References 35 publications

(59 reference statements)

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“…The efficacy of blue light inhibiting TGFβ-induced cell differentiation has been previously reported [62]. Differentiated fibroblasts known as myofibroblasts are uncommon in healthy gingival tissue and thus blue light may regulate TGFβ-induced fibroblast differentiation by modulating TGFβ1 secretion and promoting the autocrine regulation of TGFβR1 gene expression [63].…”

Section: Discussionmentioning

confidence: 94%

Photobiomodulation of oral fibroblasts stimulated with periodontal pathogens

et al. 2021

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Photobiomodulation (PBM) utilises light energy to treat oral disease, periodontitis. However, there remains inconsistency in the reporting of treatment parameters and a lack of knowledge as to how PBM elicits its molecular effects in vitro. Therefore, this study aimed to establish the potential immunomodulatory effects of blue and near infra-red light irradiation on gingival fibroblasts (GFs), a key cell involved in the pathogenesis of periodontitis. GFs were seeded in 96-well plates in media + / − Escherichia coli lipopolysaccharide (LPS 1 μg/ml), or heat-killed Fusobacterium nucleatum (F. nucleatum, 100:1MOI) or Porphyromonas gingivalis (P. gingivalis, 500:1MOI). Cultures were incubated overnight and subsequently irradiated using a bespoke radiometrically calibrated LED array (400–830 nm, irradiance: 24 mW/cm2 dose: 5.76 J/cm2). Effects of PBM on mitochondrial activity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and adenosine triphosphate (ATP) assays, total reactive oxygen species production (ROS assay) and pro-inflammatory/cytokine response (interleukin-8 (IL-8) and tumour growth factor-β1 (TGFβ1)) were assessed 24 h post-irradiation. Data were analysed using one-way ANOVA followed by the Tukey test. Irradiation of untreated (no inflammatory stimulus) cultures at 400 nm induced 15%, 27% and 13% increases in MTT, ROS and IL-8 levels, respectively (p < 0.05). Exposure with 450 nm light following application of P. gingivalis, F. nucleatum or LPS induced significant decreases in TGFβ1 secretion relative to their bacterially stimulated controls (p < 0.001). Following stimulation with P. gingivalis, 400 nm irradiation induced 14% increases in MTT, respectively, relative to bacteria-stimulated controls (p < 0.05). These findings could identify important irradiation parameters to enable management of the hyper-inflammatory response characteristic of periodontitis.

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Section: Discussionmentioning

confidence: 94%

Photobiomodulation of oral fibroblasts stimulated with periodontal pathogens

et al. 2021

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“…Transforming growth factor-β (TGF-β) is produced in the early stages of wound healing, produced by activated macrophages and neutrophils, which act as chemotactic and mitogenic factor to gingival and periodontal ligament cells, other than to be involved in the myofibroblast differentiation (Kuru et al, 2004;Yi et al, 2016). As reported by Smith et al (2006), TGF-β1 was able to bring some modifications in the adhesive properties of hGFs and may increase the expression levels of several integrins (Rout et al, 2002;Smith et al, 2006). TGF-β1 is also considered an important factor in fibrosis regulation and in the induction of the transition of fibroblast phenotype to myofibroblast in vitro by means of the Smad 3-dependent pathway (Desmouliere et al, 1993;Fang and Svoboda, 2005;Willis et al, 2006;Hinz et al, 2012).…”

Section: Discussionmentioning

confidence: 94%

“…Myofibroblasts are commonly involved in the production of ECM components, such as collagens, glycoproteins, and proteoglycans, and the augmentation of matrix elements such as laminin, glycosaminoglycans, and hyaluronic acid. In gingival tissue during the wound healing process, myofibroblasts originate from resident fibroblasts, which are stimulated by cytokines and growth factors (Rout et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor-Beta1 and Human Gingival Fibroblast-to-Myofibroblast Differentiation: Molecular and Morphological Modifications

et al. 2021

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After oral mucosal injury, the healing response following specific steps that lead to wound closure and to tissue repair. Multiple cell populations are involved in this process; in particular, fibroblasts play a key role in the production of extracellular matrix (ECM). During wound healing the remodeling of ECM is a key stage to restore the tissue functionality through multifunctional fibroblast populations that are placed in the connective tissues of gingiva and periodontal ligament. Notably, a fibroblast sub-type (myofibroblast) is centrally involved in collagen synthesis and fibrillar remodeling. The present work evidenced the role of Transforming Growth Factor-beta1 (TGF-β1) to mediate human gingival fibroblasts (hGFs) differentiation into myofibroblasts derived from gingival fibroblasts (myo-hGFs). The morphological and functional features were analyzed through Confocal Laser Scanning Microscopy (CLSM), flow cytometry, and western blotting analyses. The specific markers, such as alpha-Smooth Muscle Actin (α-SMA), Vimentin, E-cadherin, β-catenin, and Smad 2/3, were modulated in myo-hGFs after the induction with TGF-β1, at different time points (24, 48, and 72 h). After 72 h of treatment TGF-β1 operates as an inducer of hGFs into myo-hGFs differentiation. We propose that TGF-β1 may promote in vitro the fibroblasts-to-myofibroblasts transition via the morphological and molecular modifications, as the induction of α-SMA, Vimentin, E-cadherin, β-catenin, and Smad 2/3.

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“…Trans-differentiation from fibroblasts to myofibroblasts attracts attentions because of the important implications in wound healing, organ fibrosis, and regenerative medicine (Li and Wang, 2011;Smith, 2018;Tomasek et al, 2002). Although studies have demonstrated that TGF-b/Smad pathway is indispensible in vitro and in vivo for the process of fibroblasts trans-differentiation, the concrete mechanism is still unclear (Conte et al, 2014;Rodriguez et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

An intermediate state in trans-differentiation with proliferation, metabolic, and epigenetic switching

Jiang

et al. 2021

iScience

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Although TGF-b signaling can effectively activate fibroblasts to transform to myofibroblasts, the underlying mechanisms involved in the cell fate switching for trans-differentiation have not been fully elucidated. In this study, we found the evidence of an intermediate state in the process of trans-differentiation. In the early stage of trans-differentiation, cells enter the intermediate state first with multiple characteristics such as accelerating cell cycle, metabolic switching, enhanced anti-apoptotic ability, and pluripotency, which is very similar to the early stage of reprogramming. As the trans-differentiation continues, these characteristics get switched. Therefore, trans-differentiation appears to require the switching of cell proliferation ability, metabolic pathway, and ''stemness'' to complete the process. In this study, we can conclude that an intermediate state may be necessary with high pluripotency in trans-differentiation from fibroblasts to myofibroblasts. Only after passing the intermediate state, the trans-differentiation is finally completed and will not easily return to the original state.

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Role of myofibroblasts in normal and pathological periodontal wound healing

Cited by 9 publications

References 35 publications

Photobiomodulation of oral fibroblasts stimulated with periodontal pathogens

Photobiomodulation of oral fibroblasts stimulated with periodontal pathogens

Transforming Growth Factor-Beta1 and Human Gingival Fibroblast-to-Myofibroblast Differentiation: Molecular and Morphological Modifications

An intermediate state in trans-differentiation with proliferation, metabolic, and epigenetic switching

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