New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

Herlin, Maria; Finnilä, Mikko A. J.; Zioupos, Peter; Aula, Antti; Risteli, Juha; Miettinen, Hanna; Jämsä, Timo; Tuukkanen, Juha; Korkalainen, Merja; Håkansson, Helen; Viluksela, Matti

doi:10.1016/j.taap.2013.09.002

Cited by 42 publications

(44 citation statements)

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“…53 Associated with skeletal development and extracellular matrix proteins, TFIP11 is upregulated in mice after tetrachlorodibenzo-p-dioxin exposure. 54 Interestingly, TUFT1 and TFIP11 can affect the formation of dental enamel. 55 Originally isolated as proteins that induce bone and cartilage formation, BMPs are considered to comprise almost a third of TGFβ.…”

Section: Discussionmentioning

confidence: 99%

A novel role in skeletal segment regeneration of extracellular vesicles released from periodontal-ligament stem cells

Diomede

D’Aurora

Gugliandolo

et al. 2018

IJN

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PurposeThe combination of oral derived stem cells and 3-D scaffolds is considered advantageous in bone repair. In particular, collagen membranes possess ideal biological properties and can support infiltration and proliferation of osteoblasts, promoting bone regeneration. Our study aimed to develop a new biocompatible osteogenic construct composed of a commercially available collagen membrane (Evolution [Evo]), human periodontal-ligament stem cells (hPDLSCs) enriched with extracellular vesicles (EVs), or polyethylenimine (PEI)-engineered EVs (PEI-EVs).MethodsOsteogenic ability and expression of osteogenic genes were evaluated in vitro in hPDLSCs cultured with or without Evo, with Evo and EVs, or PEI-EVs. In addition, the bone-regeneration capacity of Evo, Evo enriched with hPDLSCs, Evo enriched with hPDLSCs and EVs/PEI-EVs was investigated in rats subjected to calvarial defects.ResultsOur results showed that Evo enriched with EVs and PEI-EVs showed high biocompatibility and osteogenic properties in vitro and in vivo. In addition, quantitative reverse-transcription polymerase chain reaction demonstrated the upregulation of osteogenic genes, such as TGFB1, MMP8, TUFT1, TFIP11, BMP2, and BMP4, in the presence of PEI-EVs. Upregulation of BMP2/4 was confirmed for Evo enriched with PEI-EVs and hPDLSCs both in vitro by Western blot and in vivo by immunofluorescence.ConclusionOur results indicated that Evo enriched with hPDLSCs and PEI-EVs is able to promote a bone-regeneration process for the treatment of calvarium and ossification defects caused by accidental or surgery trauma. In particular, PEI-EVs had a significant role in activation of the osteogenic process.

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Section: Discussionmentioning

confidence: 99%

A novel role in skeletal segment regeneration of extracellular vesicles released from periodontal-ligament stem cells

Diomede

D’Aurora

Gugliandolo

et al. 2018

IJN

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“…Experimental studies have demonstrated that exposure to TCDD affects bone geometry, bone densitometry, and biomechanical properties . TCDD also inhibits osteoblastic differentiation and osteoclastogenesis in vitro.…”

Section: Introductionmentioning

confidence: 99%

Actein alleviates 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin‐mediated cellular dysfunction in osteoblastic MC3T3‐E1 cells

Choi

Suh

Jung

et al. 2017

Environmental Toxicology

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The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to affect bone metabolism. We evaluated the protective effects of the triterpene glycoside actein from the herb black cohosh against TCDD-induced toxicity in MC3T3-E1 osteoblastic cells. We found that TCDD significantly reduced cell viability and increased apoptosis and autophagy in MC3T3-E1 osteoblastic cells (P < .05). In addition, TCDD treatment resulted in a significant increase in intracellular calcium concentration, mitochondrial membrane potential collapse, reactive oxygen species (ROS) production, and cardiolipin peroxidation, whereas pretreatment with actein significantly mitigated these effects (P < .05). The effects of TCDD on extracellular signal-related kinase (ERK), aryl hydrocarbon receptor, aryl hydrocarbon receptor repressor, and cytochrome P450 1A1 levels in MC3T3-E1 cells were significantly inhibited by actein. The levels of superoxide dismutase, ERK1, and nuclear factor kappa B mRNA were also effectively restored by pretreatment with actein. Furthermore, actein treatment resulted in a significant increase in alkaline phosphatase (ALP) activity and collagen content, as well as in the expression of genes associated with osteoblastic differentiation (ALP, type I collagen, osteoprotegerin, bone sialoprotein, and osterix). This study demonstrates the underlying molecular mechanisms of cytoprotection exerted by actein against TCDD-induced oxidative stress and osteoblast damage.

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“…As mentioned earlier, AHR-mediated pathways are involved during bone formation (Herlin et al , 2013) and osteoclastogenesis (Iqbal et al , 2013). During studies of mouse ES cell culture, between GD0.5 and 3.5 during the period of panmesoderm development, TCDD treatment disrupts expression of genes in the transforming growth factors-β (TGFB1/2/3), bone morphogenetic proteins-2, -4 (BMP2/4), and WNT3A/5A (wingless-type MMTV integration site members-3a and -5a)-signaling pathways; AHR-signaling specifically suppresses secretion of BMP4, WNT3A, and WNT5A.…”

Section: Ahr and Cell-signaling Pathwaysmentioning

confidence: 96%

“…AHR-signaling is now known to participate in: cell migration (Mulero-Navarro and Fernandez-Salguero, 2016), epithelial cell development (Ikuta et al , 2009), cytoskeletal/adhesion regulation (Zhang et al , 2016), circadian rhythmicity (Anderson et al , 2013), barrier organ physiology (Esser and Rannug, 2015), cardiovascular and respiratory physiology (Sauzeau et al , 2011b), kidney development (Nanez et al , 2011), inner ear cochlear development in the neonate (Safe and Luebke, 2016), bone formation (Herlin et al , 2013) and osteoclastogenesis (Iqbal et al , 2013; Izawa et al , 2016), GI tract (Hubbard et al , 2015; Schiering et al , 2016), intestinal immunity (Qiu and Zhou, 2013), innate immunity (Cella and Colonna, 2015), hematopoiesis (Lindsey and Papoutsakis, 2012; Fracchiolla et al , 2016), transgenerational inheritance (Baker et al , 2014), reproductive organ development (Mulero-Navarro and Fernandez-Salguero, 2016), regulation of female reproduction (Hernandez-Ochoa et al , 2009), prostate gland development (Schneider et al , 2014), hyperlipidemia, atherogenesis, and hypertension (Xiao et al , 2014), thyroid-associated eye disease (Woeller et al , 2016), eye and ciliary body function (Shichi and Nebert, 1982; Volotinen et al , 2009), hepatic steatosis (Mellor et al , 2016), pancreatic beta-cell regulation (Sabatini and Lynn, 2015), glucose and lipid metabolism (Gooley, 2016), circadian clock and metabolic syndrome disruption (Jaeger and Tischkau, 2016), DNA damage control (Wells et al , 2010), tumor prevention by regulating gut immunity and growth suppression in tumor cells (Ikuta et al , 2016), and protection against oxidative stress (Wölfle et al , 2014). …”

Section: Ahr and Cell-signaling Pathwaysmentioning

confidence: 99%

Aryl hydrocarbon receptor (AHR): “pioneer member” of the basic-helix/loop/helix per - Arnt - sim (bHLH/PAS) family of “sensors” of foreign and endogenous signals

Nebert

2017

Progress in Lipid Research

220

191

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The basic-helix-loop-helix Per-Arnt-Sim (bHLH/PAS) family comprises many transcription factors, found throughout all three kingdoms of life; bHLH/PAS members “sense” innumerable intracellular and extracellular “signals” — including endogenous compounds, foreign chemicals, gas molecules, redox potential, photons (light), gravity, heat, and osmotic pressure. These signals then initiate downstream signaling pathways involved in responding to that signal. The term “PAS”, abbreviation for “Per-Arnt-Sim” was first coined in 1991. Although the mouse Arnt gene was not identified until 1991, evidence of its co-transcriptional binding partner, aryl hydrocarbon receptor (AHR), was first reported in 1974 as a “sensor” of foreign chemicals, up-regulating cytochrome P450 family 1 (CYP1) and other enzyme activities that usually metabolize the signaling chemical. Within a few years, AHR was proposed also to participate in inflammation. The mouse [Ah] locus was shown (1973–1989) to be relevant to chemical carcinogenesis, mutagenesis, toxicity and teratogenesis, the mouse Ahr gene was cloned in 1992, and the first Ahr(−/−) knockout mouse line was reported in 1995. After thousands of studies from the early 1970s to present day, we now realize that AHR participates in dozens of signaling pathways involved in critical-life processes, affecting virtually every organ and cell-type in the animal, including many invertebrates.

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New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

Cited by 42 publications

References 45 publications

A novel role in skeletal segment regeneration of extracellular vesicles released from periodontal-ligament stem cells

A novel role in skeletal segment regeneration of extracellular vesicles released from periodontal-ligament stem cells

Actein alleviates 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin‐mediated cellular dysfunction in osteoblastic MC3T3‐E1 cells

Aryl hydrocarbon receptor (AHR): “pioneer member” of the basic-helix/loop/helix per - Arnt - sim (bHLH/PAS) family of “sensors” of foreign and endogenous signals

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