Insulin-like growth factor axis gene polymorphisms modify risk of pancreatic cancer

Objective: Insulin-like growth factor (IGF)-axis genes plays a critical role in cancer development and progression via their impact on the RAS/MAPK/ERK and PI3 K/AKT/mTOR signaling pathways. We hypothesized that IGF-axis genetic variants modify individual susceptibility to pancreatic cancer. Methods: We retrospectively genotyped 41 single-nucleotide polymorphisms of 10 IGF-axis genes (IGF1, IGF2, IGF1R, IGF2R, IGFBP1, IGFBP3, IGFBP5, IRS1, IRS2, and IRS4) in 706 pancreatic cancer patients and 706 cancer-free controls using Sequenom and TaqMan technology. The association between genotype and pancreatic cancer risk was evaluated using multivariate logistic regression. A P value ≤.007 at a false discovery rate of 10% was set as the significance level. Results: We observed that the IGF1 *10212C>A and Ex4+2776G>A and IGF1R IVS2?70184A>G and IVS2+46329T>C variant genotypes were significantly associated with decreased pancreatic cancer risk (odds ratio [OR] range, 0.60–0.75) and that IGFBP1 Ex4+111A>G (I253M) was significantly associated with increased pancreatic cancer risk (OR = 1.46) after adjusted for other risk factors and multiple comparisons (P ≤ .007). IGF2R and IGFBP3 variant haplotypes were associated with increased and decreased pancreatic cancer risk, respectively (P < .001). We also observed a weak interaction of the IGF1R IVS2+46329T>C and IGF2R Ex45+11C>T (L2222L) genotypes with diabetes (P_interaction = .05) and interaction of IGF2R and IRS1 genotypes with alcohol consumption (P_interaction = .03 and .019, respectively) on increased pancreatic cancer risk. Conclusion: These findings support our hypothesis that polymorphic variants of IGF-axis genes act alone or jointly with other risk factors to affect susceptibility to pancreatic cancer.     

Mechanical stress regulates osteogenic differentiation and RANKL/OPG ratio in periodontal ligament stem cells by the Wnt/β-catenin pathway

BackgroundThe balance between osteoblastic and osteoclastic activity is critical in orthodontic tooth movement (OTM). Mesenchymal stem cells (MSCs) play an important role in maintaining bone homeostasis, and periodontal ligament stem cells (PDLSCs) are tissue-specific MSCs in the periodontal ligament. However, whether PDLSCs are required for periodontal tissue remodeling during OTM is not fully understood.MethodsHere, we used PDGFRα and Nestin to trace PDLSCs during OTM in rats. We treat human PDLSCs with 100 kpa static pressure for 1 h or 12 h in vitro, and examined the phenotypic changes and expression of RANKL and OPG in these cells.ResultsIn vivo, we found that positive signals of PDGFRα and Nestin in the PDL gradually increased and then decreased on the pressure side to which pressure was applied. In vitro, the osteogenic differentiation of PDLSCs was significantly increased after force treatment for 1 h relative to 12 h. In contrast, the expression ratio of RANKL/OPG was reduced at 1 h and significantly increased at 12 h. Furthermore, we found that the Wnt/β-catenin pathway was dynamically activated in the PDL and in PDLSCs after mechanical stimulation. Importantly, the canonical Wnt pathway inhibitor DKK1 blocked the osteogenesis effect and rescued the ratio of RANKL/OPG in PDLSCs under force treatment for 1 h.ConclusionsOur findings reveal that PDLSCs participate in OTM and that the Wnt/β-catenin pathway maintains bone homeostasis during tooth movement by regulating the balance between osteoblastic and osteoclastic activity.General significanceWe describe a novel potential mechanism related to tooth movement.     

Bio-reduction of hexachloroplatinic acid to platinum nanoparticles employing Acinetobacter calcoaceticus

Acinetobacter calcoaceticus PUCM 1011 efficiently synthesized platinum nanoparticles (PtNP) of size 2–3 nm intracellularly when challenged with hexachloroplatinic acid. Salt concentration (1 mM), temperature (30 °C), pH (7) and incubation period (72 h) influenced the efficiency of monodisperse cuboidal PtNP synthesis. Resolution of ordered lattice fringes with “d” value of 0.23 nm corresponding to (1 1 1) plane and EDAX confirmed presence of metallic platinum. AFM, TEM and HR-TEM confirmed synthesis of PtNP and its effect on cell viability. Total cell protein profile for 120 h with an interval of 24 h after PtNP synthesis revealed prominent four protein bands (97, 66, 43 and 29 kDa) when compared to control. Combinations of three proteins initiated PtNP synthesis within 4 h in range of 1–4 nm and few in picometers under HR-TEM. This is the first report of PtNP synthesis employing whole cell and total cell protein of A. calcoaceticus.     

Hydroxyapatite based biocomposite scaffold: A highly biocompatible material for bone regeneration

The conventional approaches for treating bone defects such as autografts donor tissue shortages and allografts transmission of diseases pose many shortcomings. The objective of this study was to design a nano strontium/magnesium doped hydroxyapatite (Sr/Mg-HA) with chitosan (CTS) and multi-walled carbon nanotubes (MWCNT) (Sr/Mg-HA/MWCNT/CTS) biocomposite was created to support the growth of osteoblasts using a solvent evaporation method. To help the growth of osteoblasts, a solvent evaporation technique was used to design a nano strontium/magnesium doped hydroxyapatite with chitosan and multi-walled carbon nanotubes biocomposite. We studied the biocompatibility and efficiency in vitro of biocomposite following physicochemical analyzes. Tests of biocompatibility, cell proliferation, mineralization, and osteogenic differentiation have shown that in-vitro safety and effectiveness of biocomposite are good. The performance of biocomposite was more efficient in in-vitro as well as in vivo experiments than in Sr/Mg-HA nanoparticles. Briefly, the Sr/Mg-HA/MWCNT/CTS biocomposite is an ideal candidate for effective bone repair in clinics with excellent mechanical properties with durable multi-biofunctional antibacterial properties and osteoinductivity.     

Galactose-limited fed-batch cultivation of Escherichia coli for the production of lacto-N-tetraose

Lacto-N-tetraose (Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)Glc) is one of the most abundant oligosaccharide structures in human milk. We recently described the synthesis of lacto-N-tetraose by a whole-cell biotransformation with recombinant Escherichia coli cells. However, only about 5% of the lactose was converted into lacto-N-tetraose by this approach. The major product obtained was the intermediate lacto-N-triose II (GlcNAc(β1-3)Gal(β1-4)Glc).In order to improve the bioconversion of lactose to lacto-N-tetraose, we have investigated the influence of the carbon source on the formation of lacto-N-tetraose and on the intracellular availability of the glycosyltransferase substrates, UDP-N-acetylglucosamine and UDP-galactose. By growth of the recombinant E. coli cells on D-galactose, the yield of lacto-N-tetraose (810.8 mg L⁻¹ culture) was 3.6-times higher compared to cultivation on D-glucose.Using fed-batch cultivation with galactose as sole energy and carbon source, a large-scale synthesis of lacto-N-tetraose was demonstrated. During the 26 h feeding phase the growth rate (μ = 0.05) was maintained by an exponential galactose feed. In total, 16 g L⁻¹ lactose were fed and resulted in final yields of 12.72 ± 0.21 g L⁻¹ lacto-N-tetraose and 13.70 ± 0.10 g L⁻¹ lacto-N-triose II. In total, 173 g of lacto-N-tetraose were produced with a space-time yield of 0.37 g L⁻¹ h⁻¹.     

Pituitary tumor transforming gene and insulin-like growth factor 1 receptor expression and immunohistochemical measurement of Ki-67 as potential prognostic markers of pituitary tumors aggressiveness

Introduction and objectiveThe ability to predict recurrence of pituitary adenoma (PA) after surgery may be helpful to determine follow-up frequency and the need for adjuvant treatment. The purpose of this study was to assess the prognostic capacity of pituitary tumor transforming gene (PTTG), insulin-like growth factor 1 receptor (IGF1R), and Ki-67.Materials and methodsIn this retrospective study, the normalized copy number (NCN) of PTIG and IGF1R mRNA was measured using RT-PCR, and the Ki-67 index was measured by immunohistochemistry in 46 PA samples. Clinical data, histological subtype, and radiographic characteristics were collected to assess associations between variables and tumor behavior. Progression of tumor remnants and its association to markers was also studied in 14 patients with no adjuvant treatment after surgery followed up for 46 ± 36 months.ResultsExtrasellar tumors had a lower PTTG expression as compared to sellar tumors (0.065 [1st–3rd quartile: 0.000–0.089] NCN vs. 0.135 [0.105–0.159] NCN, p = 0.04). IGF1R expression changed depending on histological subtype (p = 0.014), and was greater in tumor with remnant growth greater than 20% during follow-up (10.69 ± 3.84 NCN vs. 5.44 ± 3.55 NCN, p = 0.014).ConclusionsOur results suggest that the IGF1R is a more helpful molecular marker than PTTG in PA management. Ki-67 showed no association to tumor behavior. However, the potential of these markers should be established in future studies with standardized methods and on larger samples.     

Effect of moist heat treatment on in-vitro degradability and ruminal escape protein and amino acids of mustard meal

A study was conducted to determine the effects of moist heat treatment (127°C, 117 kPa steam pressure) for 10 min on protein fractions and in-vitro crude protein (CP) degradability of mustard meal. Rumen undegraded protein (RUP) and amino acid disappearance of unheated, and heated, mustard meal were measured following 12 h of rumen incubation using two ruminally fistulated cows. Intestinal availability of RUP was estimated using an enzymatic (pepsin–pancreatin) procedure. Heat treatment reduced (p<0.05) protein solubility and increased (p<0.05) neutral detergent insoluble CP without affecting acid detergent insoluble CP of mustard meal. Relative to the control, heated mustard meal had a lower (p<0.05) effective in-vitro CP degradability (445.2 vs. 746.8 g kg⁻¹ of CP) and a higher (p<0.05) ruminal escape CP (615.1 vs. 120.2 g kg⁻¹ of CP) value. Amino acid composition was not affected by heat treatment except for the concentration of arginine and lysine which was lower (p<0.05) in heated than in unheated mustard meal. Disappearance of all amino acids following 12 h of rumen incubation was lower (p<0.05) in unheated than in heated mustard meal. Heat treatment increased (p<0.05) the amount of protein available for digestion in the small intestine from 75.7 to 518.1 g kg⁻¹ of CP. It was concluded that moist heating of mustard meal for 10 min will reduce ruminal CP and amino acid degradability without compromising the intestinal availability of ruminal undegraded protein.     

Vitamin E and rutin synergistically inhibit expression of vascular endothelial growth factor through down-regulation of binding activity of activator protein-1 in human promyelocytic leukemia (HL-60) cells

Reactive oxygen species (ROS) are strong inducers of the angiogenic hormone vascular endothelial growth factor (VEGF). Although, rutin (R) in combination with vitamin E (VE) has been shown to synergistically inhibit oxidative damage, it is unclear whether the combination of R and VE (R + VE) inhibits VEGF secretion in tumor cells. Using a human promyelocytic leukemia (HL-60) cell line, we showed that R in combination with VE synergistically decreased the expressions of VEGF protein and mRNA. We also demonstrated that R + VE significantly decreased the binding capacity of nuclear factor-activator protein-1 (AP-1) to the VEGF gene promoter and decreased the expression of c-Jun protein. Furthermore, we demonstrated that R + VE synergistically reduced insulin receptor substrate-1 (IRS-1) protein expression in HL-60 cells. The decrease of ROS was only partially associated with the decrease of VEGF secreted (r² = 0.12, P = 0.083). Thus, the present results indicate that R in combination with VE attenuates VEGF expression in HL-60 cells and that this effect is mediated by a decreased binding activity of AP-1 through down-regulation of protein expression of insulin-like growth factor 1 receptor (IGF1-R)/IRS-1, while the antioxidant activity of R + VE appears to play a minor role.     

Catalytic antioxidant AEOL 10150 treatment ameliorates sulfur mustard analog 2-chloroethyl ethyl sulfide-associated cutaneous toxic effects

Our previous studies and other published reports on the chemical warfare agent sulfur mustard (SM) and its analog 2-chloroethyl ethyl sulfide (CEES) have indicated a role of oxidative stress in skin injuries caused by these vesicating agents. We examined the effects of the catalytic antioxidant AEOL 10150 in the attenuation of CEES-induced toxicity using our established skin injury models (skin epidermal cells and SKH-1 hairless mice) to validate the role of oxidative stress in the pathophysiology of mustard vesicating agents. Treatment of mouse epidermal JB6 and human HaCaT cells with AEOL 10150 (50 μM) 1 h post-CEES exposure resulted in significant (p < 0.05) reversal of CEES-induced decreases in both cell viability and DNA synthesis. Similarly, AEOL 10150 treatment 1 h after CEES exposure attenuated CEES-induced DNA damage in these cells. Similar AEOL 10150 treatments also caused significant (p < 0.05) reversal of CEES-induced decreases in cell viability in normal human epidermal keratinocytes. Cytoplasmic and mitochondrial reactive oxygen species measurements showed that AEOL 10150 treatment drastically ameliorated the CEES-induced oxidative stress in both JB6 and HaCaT cells. Based on AEOL 10150 pharmacokinetic studies in SKH-1 mouse skin, mice were treated with a topical formulation plus subcutaneous injection (5 mg/kg) of AEOL 10150 1 h after CEES (4 mg/mouse) exposure and every 4 h thereafter for 12 h. This AEOL 10150 treatment regimen resulted in over 50% (p < 0.05) reversal of CEES-induced skin bi-fold and epidermal thickness, myeloperoxidase activity, and DNA oxidation in mouse skin. Results from this study demonstrate the potential therapeutic efficacy of AEOL 10150 against CEES-mediated cutaneous lesions, supporting AEOL 10150 as a medical countermeasure against SM-induced skin injuries.     

Impact of 1.8-GHz radiofrequency radiation (RFR) on DNA damage and repair induced by doxorubicin in human B-cell lymphoblastoid cells

In the present in vitro study, a comet assay was used to determine whether 1.8-GHz radiofrequency radiation (RFR, SAR of 2 W/kg) can influence DNA repair in human B-cell lymphoblastoid cells exposed to doxorubicin (DOX) at the doses of 0 μg/ml, 0.05 μg/ml, 0.075 μg/ml, 0.10 μg/ml, 0.15 μg/ml and 0.20 μg/ml. The combinative exposures to RFR with DOX were divided into five categories. DNA damage was detected at 0 h, 6 h, 12 h, 18 h and 24 h after exposure to DOX via the comet assay, and the percent of DNA in the tail (% tail DNA) served as the indicator of DNA damage. The results demonstrated that (1) RFR could not directly induce DNA damage of human B-cell lymphoblastoid cells; (2) DOX could significantly induce DNA damage of human B-cell lymphoblastoid cells with the dose–effect relationship, and there were special repair characteristics of DNA damage induced by DOX; (3) E–E–E type (exposure to RFR for 2 h, then simultaneous exposure to RFR and DOX, and exposure to RFR for 6 h, 12 h, 18 h and 24 h after exposure to DOX) combinative exposure could obviously influence DNA repair at 6 h and 12 h after exposure to DOX for four DOX doses (0.075 μg/ml, 0.10 μg/ml, 0.15 μg/ml and 0.20 μg/ml) in human B-cell lymphoblastoid cells.     

Metformin inhibition of mTORC1 activation,DNA synthesis and proliferation in pancreatic cancer cells: Dependence on glucose concentration and role of AMPK

Metformin, a widely used anti-diabetic drug, is emerging as a potential anticancer agent but the mechanisms involved remain incompletely understood. Here, we demonstrate that the potency of metformin induced AMPK activation, as shown by the phosphorylation of its substrates acetyl-CoA carboxylase (ACC) at Ser⁷⁹ and Raptor at Ser⁷⁹², was dramatically enhanced in human pancreatic ductal adenocarcinoma (PDAC) cells PANC-1 and MiaPaCa-2 cultured in medium containing physiological concentrations of glucose (5 mM), as compared with parallel cultures in medium with glucose at 25 mM. In physiological glucose, metformin inhibited mTORC1 activation, DNA synthesis and proliferation of PDAC cells stimulated by crosstalk between G protein-coupled receptors and insulin/IGF signaling systems, at concentrations (0.05–0.1 mM) that were 10–100-fold lower than those used in most previous reports. Using siRNA-mediated knockdown of the α₁ and α₂ catalytic subunits of AMPK, we demonstrated that metformin, at low concentrations, inhibited DNA synthesis through an AMPK-dependent mechanism. Our results emphasize the importance of using medium containing physiological concentrations of glucose to elucidate the anticancer mechanism of action of metformin in pancreatic cancer cells and other cancer cell types.     

The effect of provocative tests on electrodiagnosis criteria in clinical carpal tunnel syndrome

Introduction and objectiveNerve conduction study is the most sensitive test for diagnosis of carpal tunnel syndrome (CTS). This test is normal in some patients with mild CTS. Median nerve conduction study evaluation after a provocative test (e.g. wrist flexion) may be helpful for diagnosis of mild CTS. This study aimed to determine the effect of wrist flexion on median nerve conduction in patients suspected to CTS and in healthy subjects.Materials and methodsIn this case-control study, 20 patients (20 hands) with clinical signs of CTS and normal routine electrodiagnosis test results and 20 healthy subjects were investigated. Measured parameters included: median nerve distal sensory latency (DSL), nerve conduction velocity (NCV) across wrist, compound nerve action potential (CNAP), distal motor latency (DML) and compound muscle action potential amplitude (CAMPAMP). The above noted parameters were measured before and after 5 min of full wrist flexion. Data were analyzed using paired T-test.ResultsDistal sensory latency increment and NCV decrimental after 5 min of wrist flexion in the patients group were statistically significant (p < 0.01). The same parameters did not show significant incremental or detrimental changes in the control group.ConclusionMedian nerve DSL and NCV measurement after 5 min of wrist flexion may be helpful in determining more sensitive parameters in the electrodiagnosis of CTS.     

Computational and clinical investigation on the role of mechanical vibration on orthodontic tooth movement

The aim of this study is to investigate the biomechanics for orthodontic tooth movement (OTM) subjected to concurrent single-tooth vibration (50 Hz) with conventional orthodontic force application, via a clinical study and computational simulation. Thirteen patients were recruited in the clinical study, which involved distal retraction of maxillary canines with 1.5 N (150 g) force for 12 weeks. In a split mouth study, vibration and non-vibration sides were randomly assigned to each subject. Vibration of 50 Hz, of approximately 0.2 N (20 g) of magnitude, was applied on the buccal surface of maxillary canine for the vibration group. A mode-based steady-state dynamic finite element analysis (FEA) was conducted based on an anatomically detailed model, complying with the clinical protocol. Both the amounts of space closure and canine distalization of the vibration group were significantly higher than those of the control group, as measured intra-orally or on models (p < 0.05). Therefore it is indicated that a 50 Hz and 20 g single-tooth vibration can accelerate maxillary canine retraction. The volume-average hydrostatic stress (VHS) in the periodontal ligament (PDL) was computationally calculated to be higher with vibration compared with the control group for maxillary teeth and for both linguo-buccal and mesial-distal directions. An increase in vibratory frequency further amplified the PDL response before reaching a local natural frequency. An amplification of PDL response was also shown to be induced by vibration based on computational simulation. The vibration-enhanced OTM can be described by mild, vigorous and diminishing zones among which the mild zone is considered to be clinically beneficial.     

Green biosynthesis of silver nanoparticles from Annona squamosa leaf extract and its in vitro cytotoxic effect on MCF-7 cells

The biological method for the synthesis of silver nanoparticles (AgNPs) using Annona squamosa leaf extract and its cytotoxicity against MCF-7 cells are reported. The synthesized AgNPs using A. squamosa leaf extract was determined by UV–visible spectroscopy and it was further characterized by FT-IR, X-ray diffraction (XRD), Transmission electron microscopy (TEM), Zeta potential and energy dispersive spectrometric (EDS) analysis. The UV–visible spectrum showed an absorption peak at 444 nm which reflects surface plasmon resonance (SPR) of AgNPs. TEM photography showed biosynthesized AgNPs were predominantly spherical in shape with an average size ranging from 20 to 100 nm. The Zeta potential value of ?37 mV revealed the stability of biosynthesized AgNPs. Furthermore, the green synthesized AgNPs exhibited a dose-dependent cytotoxicity against human breast cancer cell (MCF-7) and normal breast epithelial cells (HBL-100) and the inhibitory concentration (IC₅₀) were found to be 50 μg/mL, 30 μg/mL, and 80 μg/mL, 60 μg/ml for AgNPs against MCF-7 and normal HBL-100 cells at 24 h and 48 h incubation respectively. An induction of apoptosis was evidenced by (AO/EtBr) and DAPI staining. Application of such eco-friendly nanoparticles makes this method potentially exciting for the large scale synthesis of nanoparticles.     

Role of serum concentration of VEGFR1 and TIMP2 on clinical outcome in primary cervical cancer: Results of a companion protocol of the randomized,NOGGO–AGO phase III adjuvant trial of simultaneous cisplatin-based radiochemotherapy vs. carboplatin and paclitaxel containing sequential radiotherapy

ObjectiveAim of the present study was to analyze the expression-profile of IGF1, IGFBP3, sICAM1, sVCAM1, MMP2, MMP9, TIMP2, VEGFA, VEGFD, VEGFC and VEGFR1 in patients with high-risk FIGO-stage Ib-IIb cervical cancer.MethodsSerum from 68 cervical cancer patients treated within a phase-III-trial with either simultaneous cisplatin radiochemotherapy or sequential systemic carboplatin and paclitaxel followed by percutaneous irradiation was analyzed by ELISA. Both target expression and correlation with important clinicopathological factors were analyzed following standard statistic procedures.ResultsAll 68 patients underwent a primary radical hysterectomy with pelvic and/or paraaortic lymphadenectomy. 85.3% of the extirpated tumors had clear surgical margins (R0). Increased levels of VEGFR1, TIMP2 and MMP2 were significantly associated with positive surgical margins (p = 0.004, p = 0.018 and p = 0.004, respectively). High concentration of MMP2 and TIMP2 correlated additionally with an advanced age at time of diagnosis (p = 0.001 and p = 0.007, respectively). For the cut-off value of 100 pg/ml, an increased VEGFR1 was significantly associated with poor overall (OS) and progression-free (PFS) survival (p = 0.017 and p = 0.015, respectively). A TIMP2 concentration of lower than 90 ng/ml was significantly associated with poorer OS and PFS (p = 0.009 and p = 0.043, respectively). In the multivariate analysis, TIMP2 expression in serum was the only independent prognostic factor for OS (p = 0.032, HR = 6.51, 95% CI = 1.17–36.01).ConclusionsExpression-profile of specific biomarkers associated with tumor invasion, cell migration and angiogenesis seems to be of prognostic value for both OS and PFS in patients undergoing surgery due to primary cervical cancer. Further analyses are warranted to allow an implementation of such markers into clinical practice.     

Ear fibroblasts derived from Taiwan yellow cattle are more heat resistant than those from Holstein cattle

The objective of this study was to compare the thermotolerances of ear fibroblasts derived from Holstein (H) and Taiwan yellow cattle (Y) and their apoptosis-related protein expressions with (1, 3, 6, 12, and 24 h) or without heat shock treatment. The results showed that the vaginal temperatures of Y (38.4–38.5 °C) were (P<0.05) lower than that of H (38.8 °C) during the hot season. The apoptotic rates of ear fibroblasts derived from Y (6 h: 1.1%; 12 h: 1.6%; 24 h: 2.6%) were lower (P<0.05) than those of cells derived from H (6 h: 1.8%; 12 h: 4.0%; 24 h: 6.9%), respectively, after heat shock (42 °C). The expression level of apoptosis inducing factor (AIF) in ear fibroblasts derived from H was higher (P<0.05) than those derived from Y after the heat shock treatment for 6 h and 12 h, respectively. The level of cytochrome c of ear fibroblasts derived from H was higher (P<0.05) than those derived from Y after the heat shock treatment for 1–12 h, respectively. The abundances of Caspase-3, Caspase-8 and Caspase-9 of ear fibroblasts derived from H were higher (P<0.05) than those of cells derived from Y after 12 h and 24 h of heat shock, respectively; the Bcl-2/Bax ratios of ear fibroblasts derived from H were lower (P<0.05) than those from Y-derived fibroblasts after heated for 1–24 h. The expression level of HSP-70 of Y-derived ear fibroblasts was also higher (P<0.05) than that from H after the same duration of heat shock treatments. Taken together, the thermotolerance of ear fibroblasts derived from Taiwan yellow cattle was better than that of cells derived from Holstein cattle.     

Hydro-mechanical coupling in the periodontal ligament: A porohyperelastic finite element model

Harmonic tension–compression tests at 0.1, 0.5 and 1 Hz on hydrated bovine periodontal ligament (PDL) were numerically simulated. The process was modeled by finite elements (FE) within the framework of poromechanics, with the objective of isolating the contributions of the solid- and fluid phases. The solid matrix was modeled as a porous hyperelastic material (hyperfoam) through which the incompressible fluid filling the pores flowed in accordance with the Darcy’s law. The hydro-mechanical coupling between the porous solid matrix and the fluid phase circulating through it provided an apparent time-dependent response to the PDL, whose rate of deformation depended on the permeability of the porous solid with respect to the interstitial fluid. Since the PDL was subjected to significant deformations, finite strains were taken into account and an exponential dependence of PDL permeability on void ratio – and therefore on the deformation state – was assumed. PDL constitutive parameters were identified by fitting the simulated response to the experimental data for the tests at 1 Hz. The values thus obtained were then used to simulate the tests at 0.1 and 0.5 Hz. The results of the present simulation demonstrate that a porohyperelastic model with variable permeability is able to describe the two main aspects of the PDL’s response: (1) the dependency on strain-rate—the saturated material can develop volumetric strains by only exchanging fluid and (2) the asymmetry between tension and compression, which is due to the effect of both the permeability and the elastic properties on deformation.