Calreticulin silencing inhibits extracellular matrix synthesis of human gingival fibroblasts cultured on three-dimensional poly(lactic-co-glycolic acid) scaffolds by inhibiting the calcineurin/nuclear factor of activated T cells 3 signalling pathway

Wei, Hui; Chen, Zhuo; Zheng, Yuanyuan; Chen, Qun; Min, Hsuyin; Ma, Qinqin; Gao, Biyun; Mo, Shuixue

doi:10.1016/j.aanat.2021.151820

Cited by 4 publications

(3 citation statements)

References 42 publications

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“…Considering the Ca 2+ buffering nature of CRT, studies by others and us all agree with the proapoptotic nature of abnormally high level of CRT [25]. It has been revealed that mechanical loading (compressive or tensile) could trigger CRT expression, while mechanical unloading ameliorated it, in various cell types [26][27][28][29]. However, the mechanism through which mechanical stimuli could modulate CRT expression in these cells have not been elucidated.…”

Section: Discussionmentioning

confidence: 78%

Intensive stretch-activated CRT-PMCA1 feedback loop promoted Ca2+ overloading and apoptosis of myoblasts

Liu

Xiao

Zhang

et al. 2022

Preprint

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Background Mechanical stretch exerted pro-apoptotic effect on myoblasts, the mechanism of which is currently unknown. Intracellular Ca2+ accumulation has been implicated in stretch-induced apoptosis. calreticulin (CRT) and plasma membrane Ca2+ transporting ATPase 1 (PMCA1) are two critical components of Ca2+ signaling system participating in intracellular Ca2+ homeostasis. In this study, we explored the contribution of CRT and PMCA1 in mediating stretch-induced Ca2+ accumulation and apoptosis of myoblasts. Results Stretching stimuli elevated level of CRT while inhibited activity of PMCA1. Moreover, there were bidirectional regulations between CRT and PMCA1, which formed the positive feedback loop leading to continuous increment of CRT level and repression of PMCA1 activity, in stretched myoblasts. Specifically, increased CRT level inhibited PMCA1 activity via suppressing Calmodulin (CaM), while reduced PMCA1 activity promoted CRT expression through activating p38MAPK pathway. Thus, the CRT-CaM-PMCA1 and PMCA1-p38MAPK-CRT pathways constituted a close cycle comprising CRT, PMCA1, CaM and p38MAPK. Inhibition of both CaM and p38MAPK affected the other three factors in stretched myoblasts. Circulation of the vicious cycle resulted in escalated Ca2+ overloading in myoblasts under continuous stretching stimuli. CRT knock-down, PMCA1 overexpression, and p38MAPK inhibition all attenuated the raised intracellular Ca2+ level and ameliorated myoblast apoptosis in the stretching environment. Conversely, CRT overexpression, PMCA1 knock-down, and CaM inhibition all aggravated stretch-induced Ca2+ overloading and myoblast apoptosis. Conclusions A positive feedback loop between CRT and PMCA1 was activated in stretched myoblasts, which contributed to intracellular Ca2+ accumulation and resultant myoblast apoptosis.

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Section: Discussionmentioning

confidence: 78%

Intensive stretch-activated CRT-PMCA1 feedback loop promoted Ca2+ overloading and apoptosis of myoblasts

Liu

Xiao

Zhang

et al. 2022

Preprint

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“…In addition to biodegradability, biocompatibility and good mechanical properties, PLGA has a controllable degradation rate [17]. Due to their properties, PLGA scaffolds are actively used for gingival tissue regeneration [18,19].…”

Section: Introductionmentioning

confidence: 99%

Surface Modification of Electrospun Bioresorbable and Biostable Scaffolds by Pulsed DC Magnetron Sputtering of Titanium for Gingival Tissue Regeneration

et al. 2022

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In this study, polymer scaffolds were fabricated from biodegradable poly(lactide-co-glycolide) (PLGA) and from non-biodegradable vinylidene fluoride-tetrafluoroethylene (VDF-TeFE) by electrospinning. These polymer scaffolds were subsequently surface-modified by sputtering titanium targets in an argon atmosphere. Direct current pulsed magnetron sputtering was applied to prevent a significant influence of discharge plasma on the morphology and mechanical properties of the nonwoven polymer scaffolds. The scaffolds with initially hydrophobic properties show higher hydrophilicity and absorbing properties after surface modification with titanium. The surface modification by titanium significantly increases the cell adhesion of both the biodegradable and the non-biodegradable scaffolds. Immunocytochemistry investigations of human gingival fibroblast cells on the surface-modified scaffolds indicate that a PLGA scaffold exhibits higher cell adhesion than a VDF-TeFE scaffold.

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“…Against this background, polymer-based, biodegradable biomaterials have proven suitable as scaffolds that allow the in vitro modeling of complex biological processes such as soft and hard tissue regeneration, which are both important in the context of periodontal tissue engineering [30][31][32]. Various nontoxic natural and synthetic polymers, including chitosan [33], alginate [34], collagen/gelatin [35], and polylactic [36] and polyglycolic acid [37], have been adapted for similar applications and imitate natural extracellular matrices (ECMs) [38,39]. Among them, gelatin is a natural origin protein obtained by acidic and alkaline processing of collagen type I, the main protein component of the skin, bones, and connective tissue of animals.…”

Section: Introductionmentioning

confidence: 99%

Novel In Situ-Cross-Linked Electrospun Gelatin/Hydroxyapatite Nonwoven Scaffolds Prove Suitable for Periodontal Tissue Engineering

et al. 2022

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Periodontal diseases affect millions of people worldwide and can result in tooth loss. Regenerative treatment options for clinical use are thus needed. We aimed at developing new nonwoven-based scaffolds for periodontal tissue engineering. Nonwovens of 16% gelatin/5% hydroxyapatite were produced by electrospinning and in situ glyoxal cross-linking. In a subset of scaffolds, additional porosity was incorporated via extractable polyethylene glycol fibers. Cell colonization and penetration by human mesenchymal stem cells (hMSCs), periodontal ligament fibroblasts (PDLFs), or cocultures of both were visualized by scanning electron microscopy and 4′,6-diamidin-2-phenylindole (DAPI) staining. Metabolic activity was assessed via Alamar Blue® staining. Cell type and differentiation were analyzed by immunocytochemical staining of Oct4, osteopontin, and periostin. The electrospun nonwovens were efficiently populated by both hMSCs and PDLFs, while scaffolds with additional porosity harbored significantly more cells. The metabolic activity was higher for cocultures of hMSCs and PDLFs, or for PDLF-seeded scaffolds. Periostin and osteopontin expression was more pronounced in cocultures of hMSCs and PDLFs, whereas Oct4 staining was limited to hMSCs. These novel in situ-cross-linked electrospun nonwoven scaffolds allow for efficient adhesion and survival of hMSCs and PDLFs. Coordinated expression of differentiation markers was observed, which rendered this platform an interesting candidate for periodontal tissue engineering.

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Calreticulin silencing inhibits extracellular matrix synthesis of human gingival fibroblasts cultured on three-dimensional poly(lactic-co-glycolic acid) scaffolds by inhibiting the calcineurin/nuclear factor of activated T cells 3 signalling pathway

Cited by 4 publications

References 42 publications

Intensive stretch-activated CRT-PMCA1 feedback loop promoted Ca2+ overloading and apoptosis of myoblasts

Intensive stretch-activated CRT-PMCA1 feedback loop promoted Ca2+ overloading and apoptosis of myoblasts

Surface Modification of Electrospun Bioresorbable and Biostable Scaffolds by Pulsed DC Magnetron Sputtering of Titanium for Gingival Tissue Regeneration

Novel In Situ-Cross-Linked Electrospun Gelatin/Hydroxyapatite Nonwoven Scaffolds Prove Suitable for Periodontal Tissue Engineering

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