Oleic acid-related anti-inflammatory effects in force-stressed PdL fibroblasts are mediated by H3 lysine acetylation associated with altered <i>IL10</i> expression

Schuldt, Lisa; Brandenstein, Katrin von; Jacobs, Collin; Symmank, Judit

doi:10.1080/15592294.2022.2090654

Cited by 12 publications

(8 citation statements)

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“…Acetylation and deacetylation are essential chemical modifications of histones, which are associated with gene expression or gene silencing [ 42 ]. It has been demonstrated that histone 3 acetylation (H3ac) is associated with IL-10 expression in force-stressed PDL fibroblasts [ 43 ]. Our research verified that H3ac is significantly elevated by compression force.…”

Section: Discussionmentioning

confidence: 99%

Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation

Wang

Groeger

Yong

et al. 2023

IJMS

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Orthodontic tooth movement is a complex periodontal remodeling process triggered by compression that involves sterile inflammation and immune responses. Macrophages are mechanically sensitive immune cells, but their role in orthodontic tooth movement is unclear. Here, we hypothesize that orthodontic force can activate macrophages, and their activation may be associated with orthodontic root resorption. After force-loading and/or adiponectin application, the migration function of macrophages was tested via scratch assay, and Nos2, Il1b, Arg1, Il10, ApoE, and Saa3 expression levels were detected using qRT-PCR. Furthermore, H3 histone acetylation was measured using an acetylation detection kit. The specific inhibitor of H3 histone, I-BET762, was deployed to observe its effect on macrophages. In addition, cementoblasts were treated with macrophage-conditioned medium or compression force, and OPG production and cellular migration were measured. We further detected Piezo1 expression in cementoblasts via qRT-PCR and Western-blot, and its effect on the force-induced impairment of cementoblastic functions was also analyzed. Compressive force significantly inhibited macrophage migration. Nos2 was up-regulated 6 h after force-loading. Il1b, Arg1, Il10, Saa3, and ApoE increased after 24 h. Meanwhile, higher H3 histone acetylation was detected in the macrophages subjected to compression, and I-BET762 dampened the expression of M2 polarization markers (Arg1 and Il10). Lastly, even though the activated macrophage-conditioned medium showed no effect on cementoblasts, compressive force directly impaired cementoblastic function by enhancing mechanoreceptor Piezo1. Compressive force activates macrophages; specifically, it causes M2 polarization via H3 histone acetylation in the late stage. Compression-induced orthodontic root resorption is macrophage-independent, but it involves the activation of mechanoreceptor Piezo1.

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Section: Discussionmentioning

confidence: 99%

Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation

Wang

Groeger

Yong

et al. 2023

IJMS

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“…Immunofluorescent staining was performed as previously described [49][50][51]. Briefly, following 10 min fixation with paraformaldehyde (PFA, 4%), three washing steps in 1× PBS/0.1% Triton X (Triton X ® 100, Carl Roth GmbH + Co. KG, Karlsruhe, Germany) were applied.…”

Section: Immunofluorescent Stainingmentioning

confidence: 99%

“…To visualize the cytokine secretion of the stimulated hPdLFs, activation of the monocytic THP1 cells was performed like previously described [16,49,50,52]. Briefly, Celltracker CMFDA (15 µM, 30 min, Thermo Fisher Scientific, Carlsbad, CA, USA)-stained nonadherent THP1 cells were applied for 30 min to the hPdLFs cultured on the coverslips.…”

Section: Thp1 Activation Assaymentioning

confidence: 99%

“…The Fiji Image J software (https://imagej.net/software/fiji; accessed on 10 January 2021, version number 1.52p) was used for the image analysis. The intensity measurements of p21 Waf1/Cip1/Sdi1 , H2A.X and GDF15 were performed as previously described [49,50]. Briefly, to avoid influencing the respective expression intensities, individual experiments were microscopically scanned on the same day using pre-warmed lasers and identical settings for each treatment condition.…”

Section: Microscopy and Image Analysismentioning

confidence: 99%

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GDF15 Modulates the Zoledronic-Acid-Induced Hyperinflammatory Mechanoresponse of Periodontal Ligament Fibroblasts

Nitzsche,

Hennig,

von Brandenstein

et al. 2024

Cells

Self Cite

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Orthodontic tooth movement (OTM) is thought to be impeded by bisphosphonate (BP) therapy, mainly due to increased osteoclast apoptosis and changes in the periodontal ligament (PdL), a connecting tissue between the alveolar bone and teeth. PdL cells, mainly fibroblasts (PdLFs), are crucial regulators in OTM by modulating force-induced local inflammatory processes. Recently, we identified the TGF-β/BMP superfamily member GDF15 as an important modulator in OTM, promoting the pro-inflammatory mechanoresponses of PdLFs. The precise impact of the highly potent BP zoledronate (ZOL) on the mechanofunctionality of PdLFs is still under-investigated. Therefore, the aim of this study was to further characterize the ZOL-induced changes in the initial inflammatory mechanoresponse of human PdLFs (hPdLFs) and to further clarify a potential interrelationship with GDF15 signaling. Thus, two-day in vitro treatment with 0.5 µM, 5 µM and 50 µM of ZOL altered the cellular properties of hPdLFs partially in a concentration-dependent manner. In particular, exposure to ZOL decreased their metabolic activity, the proliferation rate, detected using Ki-67 immunofluorescent staining, and survival, analyzed using trypan blue. An increasing occurrence of DNA strand breaks was observed using TUNEL and an activated DNA damage response was demonstrated using H2A.X (phosphoS139) staining. While the osteogenic differentiation of hPdLFs was unaffected by ZOL, increased cellular senescence was observed using enhanced p21Waf1/Cip1/Sdi1 and β-galactosidase staining. In addition, cytokine-encoding genes such as IL6, IL8, COX2 and GDF15, which are associated with a senescence-associated secretory phenotype, were up-regulated by ZOL. Subsequently, this change in the hPdLF phenotype promoted a hyperinflammatory response to applied compressive forces with an increased expression of the pro-inflammatory markers IL1β, IL6 and GDF15, as well as the activation of monocytic THP1 cells. GDF15 appeared to be particularly relevant to these changes, as siRNA-mediated down-regulation balanced these hyperinflammatory responses by reducing IL-1β and IL-6 expression (IL1B p-value < 0.0001; IL6 p-value < 0.001) and secretion (IL-1β p-value < 0.05; IL-6 p-value < 0.001), as well as immune cell activation (p-value < 0.0001). In addition, ZOL-related reduced RANKL/OPG values and inhibited osteoclast activation were enhanced in GDF15-deficient hPdLFs (both p-values < 0.0001; all statistical tests: one-way ANOVA, Tukey’s post hoc test). Thus, GDF15 may become a promising new target in the personalized orthodontic treatment of bisphosphonatepatients.

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“…Fatty acids could serve as an alternative source of acetyl-CoA, thereby affecting epigenetic histone marks, such as histone 3 lysine acetylation. Recently, Schuldt et al demonstrated that OA-related anti-inflammatory effects in fibroblasts are mediated by histone 3 lysine acetylation associated with increased expressions of anti-inflammatory cytokines [ 114 ]. These results suggest that OA effects could be exerted by different mechanism by histone acetyltranferase activation and SIRT-1-independence [ 115 ].…”

Section: Oleic Acid and Epigeneticsmentioning

confidence: 99%

Update on Anti-Inflammatory Molecular Mechanisms Induced by Oleic Acid

et al. 2023

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In 2010, the Mediterranean diet was recognized by UNESCO as an Intangible Cultural Heritage of Humanity. Olive oil is the most characteristic food of this diet due to its high nutraceutical value. The positive effects of olive oil have often been attributed to its minor components; however, its oleic acid (OA) content (70–80%) is responsible for its many health properties. OA is an effective biomolecule, although the mechanism by which OA mediates beneficial physiological effects is not fully understood. OA influences cell membrane fluidity, receptors, intracellular signaling pathways, and gene expression. OA may directly regulate both the synthesis and activities of antioxidant enzymes. The anti-inflammatory effect may be related to the inhibition of proinflammatory cytokines and the activation of anti-inflammatory ones. The best-characterized mechanism highlights OA as a natural activator of sirtuin 1 (SIRT1). Oleoylethanolamide (OEA), derived from OA, is an endogenous ligand of the peroxisome proliferator-activated receptor alpha (PPARα) nuclear receptor. OEA regulates dietary fat intake and energy homeostasis and has therefore been suggested to be a potential therapeutic agent for the treatment of obesity. OEA has anti-inflammatory and antioxidant effects. The beneficial effects of olive oil may be related to the actions of OEA. New evidence suggests that oleic acid may influence epigenetic mechanisms, opening a new avenue in the exploration of therapies based on these mechanisms. OA can exert beneficial anti-inflammatory effects by regulating microRNA expression. In this review, we examine the cellular reactions and intracellular processes triggered by OA in T cells, macrophages, and neutrophils in order to better understand the immune modulation exerted by OA.

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Oleic acid-related anti-inflammatory effects in force-stressed PdL fibroblasts are mediated by H3 lysine acetylation associated with altered IL10 expression

Cited by 12 publications

References 69 publications

Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation

Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation

GDF15 Modulates the Zoledronic-Acid-Induced Hyperinflammatory Mechanoresponse of Periodontal Ligament Fibroblasts

Update on Anti-Inflammatory Molecular Mechanisms Induced by Oleic Acid

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