Substrate stiffness controls proinflammatory responses in human gingival fibroblasts

Tiskratok, Watcharaphol; Yamada, Masahiro; Watanabe, Jun; Kartikasari, Nadia; Kimura, Tsuyoshi; Egusa, Hiroshi

doi:10.1038/s41598-023-28541-z

Cited by 8 publications

(18 citation statements)

References 50 publications

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“… 31 During proliferation, these cell activities additionally change the microenvironment, which in turn may affect the cell responses, suggesting the potential involvement of a feedback loop. 32 − 34 In this study, an effect of stiffness on vaginal fibroblast behavior was possibly reflected in the cell morphologies, where an initially higher stiffness slightly increased spreading area on day 1. Furthermore, stiffer PIC-gels promoted fibroblast alignment and directionality, which can be explained by traction on fibroblast focal adhesions at an increased substrate stiffness.…”

Section: Discussionmentioning

confidence: 65%

Vaginal Fibroblast Behavior as a Function of Stiffness Changes in a Polyisocyanide Hydrogel for Prolapse Repair

Gudde,

van Velthoven,

Türkel

et al. 2023

ACS Appl. Bio Mater.

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There is an urgent need for improved outcomes in the treatment of pelvic organ prolapse (POP). Success of primary surgery relies on the load bearing capacity of plicated connective tissue underneath the vaginal wall, which is compromised due to an altered vaginal fibroblast function and collagen composition. There is an important factor in connective tissue repair that relates to changes in stiffness of the vaginal fibroblast microenvironment, which influences cell activity through cellular mechanosensing. The aim of this study is to investigate the effect of stiffness changes on vaginal fibroblast functions that relate to connective tissue healing in prolapse repair. The substrate stiffness was controlled by changing the polymer concentration in the fibrous and strongly biomimetic polyisocyanide (PIC) hydrogel. We analyzed stiffness during cell culture and assessed the consequential fibroblast proliferation, morphology, collagen deposition, and contraction. Our results show that increasing stiffness coincides with vaginal fibroblast alignment, promotes collagen deposition, and inhibits PIC gel contraction. These findings suggest that the matrix stiffness directly influences vaginal fibroblast functionality. Moreover, we observed a buildup in stiffness and collagen, with an enhanced fibroblast and collagen organization on the PIC-substrate, which indicate an enhanced structural integrity of the hydrogel-cell construct. An improved tissue structure during healing is relevant in the functional repair of POP. Therefore, this study encourages future research in the use of PIC gels as a supplement in prolapse surgery, whereby the hydrogel stiffness should be considered.

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Section: Discussionmentioning

confidence: 65%

Vaginal Fibroblast Behavior as a Function of Stiffness Changes in a Polyisocyanide Hydrogel for Prolapse Repair

Gudde,

van Velthoven,

Türkel

et al. 2023

ACS Appl. Bio Mater.

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“…The stiffness of the local environment can tune cellular inflammatory responses through mechanotransduction [ 55 ]. When the hGFs were cultured on substrates with different stiffnesses (soft (5 kPa) or hard (25 kPa)), the expression of PTGES2 and IL-1β was significantly enhanced in the soft substrate group compared to that in the hard substrate group [ 56 ]. Cultured mouse monocytes with different substrate stiffnesses showed higher expression of Nos2 as stiffness increased [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the results showing that the dual-cured resin cement with residual monomers induced inflammatory responses in the periodontal tissue cells are valuable for understanding the biological phenomenon around the margin of prostheses at a molecular level. On the other hand, the primary gingival fibroblasts from only one donor were used in this study because the primary cells from two donors, including those used in this study, showed similar inflammatory responses in the previous study [ 56 ]. However, the cells from multiple donors should be used in further studies.…”

Section: Discussionmentioning

confidence: 99%

Incomplete Polymerization of Dual-Cured Resin Cement Due to Attenuated Light through Zirconia Induces Inflammatory Responses

Kondo,

Kakinuma,

Fujimura

et al. 2023

IJMS

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Zirconia restorations are becoming increasingly common. However, zirconia reduces the polymerization of dual-cured resin cement owing to light attenuation, resulting in residual resin monomers. This study investigated the effects of dual-cured resin cement, with incomplete polymerization owing to attenuated light through zirconia, on the inflammatory response in vitro. The dual-cured resin cement (SA Luting Multi, Kuraray) was light-irradiated through zirconia with three thickness diameters (1.0, 1.5, and 2.0 mm). The light transmittance and the degree of conversion (DC) of the resin cement significantly decreased with increasing zirconia thickness. The dual-cured resin cement in 1.5 mm and 2.0 mm zirconia and no-irradiation groups showed significantly higher amounts of hydroxyethylmethacrylate and triethyleneglycol dimethacrylate elution and upregulated gene expression of proinflammatory cytokines IL-1β and IL-6 from human gingival fibroblasts (hGFs) and TNFα from human monocytic cells, compared with that of the 0 mm group. Dual-cured resin cement with lower DC enhanced intracellular reactive oxygen species (ROS) levels and activated mitogen-activated protein (MAP) kinases in hGFs and monocytic cells. This study suggests that dual-cured resin cement with incomplete polymerization induces inflammatory responses in hGFs and monocytic cells by intracellular ROS generation and MAP kinase activation.

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“…Although most of these studies have focused on the differentiation of fibroblasts into myo-like, ECM-producing fibrotic phenotypes, little is known about how matrix stiffness may affect other fibroblast responses. In a recent report, oral cavity fibroblasts displayed lower expression of IL-1β when cultured on stiff matrix and a modest reduction in IL-6 and IL-1β expression in response to lipopolysaccharide when cultured in a hard matrix (Tiskratok;. However, the knowledge of the effects that the fibrotic ECM may have on the ability of fibroblasts to sustain homeostatic signals or undergo inflammatory differentiation remains limited and represents an interesting area for future investigation.…”

Section: Ecmmentioning

confidence: 99%

Novel fibroblast phenotypes in homeostasis and chronic inflammation: From functions to potential regulators

Miki

Manresa

2023

The Journal of Physiology

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Fibroblasts are essential components of the stroma, sustaining a variety of tissues and being key to the process of tissue repair after injury. Their role in tissue repair has been attributed to their ability to acquire a contractile, extracellular matrix‐producing phenotype known as myofibroblasts. This property is primarily dependent on their response to the pleiotropic cytokine transforming growth factor‐β1. Until recently, the potential role of fibroblasts in other homeostatic and disease‐related processes was less well understood. Although in vitro studies indicated that fibroblasts are able to respond to and secrete inflammatory mediators, definitive evidence of their contribution to chronic inflammation was limited. However, the emergence of techniques that allow exploration of tissues at the single cell level has challenged the previous paradigms on fibroblast identity and functions, and has led to the discovery of significant diversity, showing the presence of fibroblasts with alternate transcriptional profiles in a variety of tissues. These studies have also suggested potential roles of novel fibroblast subtypes as regulators of epithelial homeostasis and renewal, inflammatory cell infiltration and activation, and antigen presentation. Here, we provide a comprehensive review of the recent literature on fibroblast diversity in the digestive tract, skin, lungs and joints. We also review evidence of their contribution to the regulation of homeostasis and chronic inflammation, as well as their interactions with other cells in various tissue compartments. We discuss evidence of different factors involved in the control of fibroblast function, addressing the role of various cytokines, transcription factors and epigenetic changes, as well as microenvironmental factors, including extracellular matrix stiffness, hypoxia, and metabolic shifts.

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Substrate stiffness controls proinflammatory responses in human gingival fibroblasts

Cited by 8 publications

References 50 publications

Vaginal Fibroblast Behavior as a Function of Stiffness Changes in a Polyisocyanide Hydrogel for Prolapse Repair

Vaginal Fibroblast Behavior as a Function of Stiffness Changes in a Polyisocyanide Hydrogel for Prolapse Repair

Incomplete Polymerization of Dual-Cured Resin Cement Due to Attenuated Light through Zirconia Induces Inflammatory Responses

Novel fibroblast phenotypes in homeostasis and chronic inflammation: From functions to potential regulators

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