Rank Expressions Research Articles

Multi-criteria constrained interval type-2 fuzzy decision-making: A space analysis perspective

Practical decision-making problems invariably involve inherent uncertainty in information, making it challenging to obtain precise evaluations. In this research, the utilization of constrained interval type-2 fuzzy sets (CIT2 FSs) enables the representation of complex uncertainty in decision information, and a space analysis approach, called CIT2 fuzzy multi-criteria acceptability analysis (CIT2FMAA), is proposed for conducting reliable decision-making. The CIT2FMAA introduces a novel paradigm for type-2 fuzzy decision-making, wherein CIT2 fuzzy evaluations are acknowledged as spaces of type-1 fuzzy evaluations and processed using type-1 fuzzy operations and methodologies. First, from a space analysis perspective, the type-2 fuzzy measures of logical rank expressions are formalized as CIT2 fuzzy rank acceptability indexes, and the CIT2 fuzzy rank acceptability analysis is developed to rank CIT2 fuzzy numbers. Second, the weighted average of the CIT2 fuzzy numbers is defined, and the CIT2FMAA is proposed to support uncertain multi-criteria decision-making. Subsequently, a sampling algorithm is designed for implementing CIT2 fuzzy rank acceptability analysis and CIT2FMAA. Finally, a linguistic disease diagnosis is performed to demonstrate the efficiency of CIT2FMAA. Compared to traditional type-2 fuzzy decision-making methods, CIT2FMAA is more efficient because it not only derives ranks of alternatives but also provides confidence degrees for those ranks.

RANK and RANKL Expression in Tumors of Patients with Early Breast Cancer

AbstractThe receptor activator of nuclear factor-κB (RANK) pathway was associated with the pathogenesis of breast cancer. Several studies attempted to link the RANK/RANKL pathway to prognosis; however, with inconsistent outcomes. We aimed to further contribute to the knowledge about RANK/RANKL as prognostic factors in breast cancer. Within this study, protein expression of RANK and its ligand, RANKL, in the tumor tissue was analyzed in association with disease-free survival (DFS) and overall survival (OS) in a study cohort of patients with early breast cancer.607 samples of female primary and early breast cancer patients from the Bavarian Breast Cancer Cases and Controls Study were analyzed to correlate the RANK and RANKL expression with DFS and OS. Therefore, expression was quantified using immunohistochemical staining of a tissue microarray. H-scores were determined with the cut-off value of 8.5 for RANK and 0 for RANKL expression, respectively.RANK and RANKL immunohistochemistry were assessed by H-score. Both biomarkers did not correlate (ρ = −0.04). According to molecular subtypes, triple-negative tumors and HER2-positive tumors showed a higher number of RANK-positive tumors (H-score ≥ 8.5), however, no subtype-specific expression of RANKL could be detected. Higher RANKL expression tended to correlate with a better prognosis. However, RANK and RANKL expression could not be identified as statistically significant prognostic factors within the study cohort.Tumor-specific RANK and RANKL expressions are not applicable as prognostic factors for DFS and OS, but might be associated with subtype-specific breast cancer progression.

RANK and RANKL Expression in Tumors of Patients with Early Breast Cancer

AbstractThe receptor activator of nuclear factor-κB (RANK) pathway was associated with the pathogenesis of breast cancer. Several studies attempted to link the RANK/RANKL pathway to prognosis; however, with inconsistent outcomes. We aimed to further contribute to the knowledge about RANK/RANKL as prognostic factors in breast cancer. Within this study, protein expression of RANK and its ligand, RANKL, in the tumor tissue was analyzed in association with disease-free survival (DFS) and overall survival (OS) in a study cohort of patients with early breast cancer.607 samples of female primary and early breast cancer patients from the Bavarian Breast Cancer Cases and Controls Study were analyzed to correlate the RANK and RANKL expression with DFS and OS. Therefore, expression was quantified using immunohistochemical staining of a tissue microarray. H-scores were determined with the cut-off value of 8.5 for RANK and 0 for RANKL expression, respectively.RANK and RANKL immunohistochemistry were assessed by H-score. Both biomarkers did not correlate (ρ = −0.04). According to molecular subtypes, triple-negative tumors and HER2-positive tumors showed a higher number of RANK-positive tumors (H-score ≥ 8.5), however, no subtype-specific expression of RANKL could be detected. Higher RANKL expression tended to correlate with a better prognosis. However, RANK and RANKL expression could not be identified as statistically significant prognostic factors within the study cohort.Tumor-specific RANK and RANKL expressions are not applicable as prognostic factors for DFS and OS, but might be associated with subtype-specific breast cancer progression.

The full rank expressions for the W-weighted Drazin and core-EP inverse of a matrix and their applications

The full rank expressions for the W-weighted Drazin and core-EP inverse of a matrix and their applications

N16 suppresses RANKL-mediated osteoclatogenesis by down-regulating RANK expression

N16 is an active protein existing in Pinctada martensi. Our previous studies have demonstrated that N16 inhibited osteoclast differentiation in vitro. To better understand how N16 regulates osteoclast differentiation, RAW264.7 cells, a murine monocytic cell line and murine bone marrow-derived macrophages (BMMs) were adopted. Treatment of RAW264.7 cells with RANKL activated osteoclastogenesis and N16 inhibited the formation of multinucleated osteoclasts and TRAP activity. The suppression occurred at the early stage of osteoclastogenesis. Moreover, we found that N16 inhibited PU.1 and MITF expressions, mirroring the inhibition of RANK expressions, indicating that N16 inhibited RANK expression by down-regulating the expressions of MITF and PU.1, thus preventing osteoclastogenesis.

High receptor activator of Nuclear Factor Kappa β (RANK) expression and luminal A subtype are associated with bone metastasis in patients with breast cancer

BackgroundBones are the most common distant metastasis site in breast cancer, especially in advanced stages. Bone metastasis involves continuous interaction between tumor cells, osteoblast, osteoclast, and bone matrix. There are many risk factors regarding distant metastasis sites in breast cancer patients, including breast cancer molecular subtypes and mediator known as Receptor Activator of Nuclear Factor Kappa β (RANK). In this study, we explore relationships between Luminal A breast cancer and RANK in association with bone metastasis site.MethodThis study is a cross-sectional analysis study conducted in Sanglah General Hospital, Bali Denpasar. Estimated sample size was measured using formula to hypothesize between two proportions, and obtained 34 patients as our minimal sample needed in this study. Data will be presented in 2x2 tables, consist of RANK Protein expression and molecular cancer subtype (Luminal A / Non-Luminal A) in row section and Metastasis (Bone Metastasis or Non-Bone Metastasis) in column section. Univariat analysis were done using comparative method between 2 categorical unrelated groups: Chi Square and Fisher’s Exact Test. OR values were measured and p value <0.05 considered to be significant statistically.ResultFrom these 106 patients, we used nested sampling to randomize these patients into our study sample, with total of 36 patients. The mean age of our patients is 48.64 ± 9.86 years. Luminal A subtypes tends to metastasize into bone component compared with Non-Luminal A subtypes with p value 0.041 and OR: 3.5; with 95% CI (0.82 – 14.84). Tumor with high RANK expressions tends to metastasize into bone component compared with low RANK expressions with p value 0.045 and OR 3.25; with 95% CI (0.81 – 13.03)ConclusionThere is a significant difference statistically in molecular subtype breast cancer and in RANK protein expressions between two patient groups (bone metastasis site vs other metastasis site)

Downregulation of Prdx2 Protects Osteoporosis Rats by Regulating Receptor Activator of Nuclear Factor Kappa-B/Osteoprotegerin Pathway

Osteoporosis (OP) is a bone disease caused by various causes and can be found in various stages, such as juvenile, adult, menopausal and old age. OP has the systemic, degenerative, and metabolic characteristics, which leads to loss of bone mass, structural changes, and biomechanical properties degeneration. Prdx2 is a member of the peroxiredoxase family with antioxidant effects and involved in the regulation of bone and joint diseases. However, the role of Prdx2 in OP and related mechanisms has not been elucidated. SD rats were randomly divided into 2 groups, OP group in which OP rat model was prepared by ovariectomy and sham operation group. Prdx2 siRNA was transfected into OP rats followed by analysis of the expression of Prdx2, Opn, and Osterix by real-time PCR, bone density changes by dual energy line bone densitometer, formation of mineralized nodules by Alizarin red staining, Serum osteocalcin (OC) activity by ELISA as well as RANK and osteoprotegerin (OPG) expressions by real-time PCR and Western blot. Prdx2 expression was significantly increased, bone mineral density (BMD) was reduced, mineralized nodule formation was attenuated, Opn and Osterix levels were downregulated, together with decreased serum OC activity, increased RANK expression, and declined OPG expression apparently in OP rats compared with sham group (P < 0.05). Prdx2 siRNA transfection downregulated Prdx2 and RANK levels, increased BMD, mineralized nodule formation, Opn, OPG, and Osterix levels, as well as serum OC activity in OP rats (P < 0.05). Prdx2 expression is elevated in osteoporotic rats, which is associated with decreased osteogenic differentiation and BMD, leading to osteoporosis. Downregulation of Prdx2 expression can improve osteoporosis by regulating the RANK/OPG pathway.

On fast multipole methods for Fredholm integral equations of the second kind with singular and highly oscillatory kernels

ABSTRACTThis paper considers a special boundary element method for Fredholm integral equations of the second kind with singular and highly oscillatory kernels. To accelerate the resolution of the linear system and the matrix-vector multiplication in each iteration, the fast multipole method (FMM) is applied, which reduces the complexity from to . The oscillatory integrals are calculated by the steepest decent method, whose accuracy becomes more accurate as the frequency increases. We study the role of the high-frequency w in the FMM, showing that the discretization system is more well conditioned as high-frequency w increase. Moreover, the larger w may reduce rank expressions from the kernel function, and decrease the absolute errors. At last, the optimal convergence rate of truncation is also represented in this paper. Numerical experiments and applications support the claims and further illustrate the performance of the method.

The Intrinsic and Extrinsic Implications of RANKL/RANK Signaling in Osteosarcoma: From Tumor Initiation to Lung Metastases.

Background: Osteosarcoma is the most frequent form of malignant pediatric bone tumor. Despite the current therapeutic arsenal, patient life-expectancy remains low if metastases are detected at the time of diagnosis, justifying research into better knowledge at all stages of osteosarcoma ontogenesis and identification of new therapeutic targets. Receptor Activator of Nuclear factor κB (RANK)expression has been reported in osteosarcoma cells, raising the question of Receptor Activator of Nuclear factor κB Ligand (RANKL)/RANK signaling implications in these tumor cells (intrinsic), in addition to previously reported implications through osteoclast activation in the tumor microenvironment (extrinsic). Methods: Based on in vitro and in vivo experimentations using human and mouse osteosarcoma cell lines, the consequences on the main cellular processes of RANK expression in osteosarcoma cells were analyzed. Results: The results revealed that RANK expression had no impact on cell proliferation and tumor growth, but stimulated cellular differentiation and, in an immune-compromised environment, increased the number of lung metastases. The analysis of RANKL, RANK and osteoprotegerin (OPG) expressions in biopsies of a cohort of patients revealed that while RANK expression in osteosarcoma cells was not significantly different between patients with or without metastases at the time of diagnosis, the OPG/RANK ratio decreased significantly. Conclusion: Altogether, these results are in favor of RANKL-RANK signaling inhibition as an adjuvant for the treatment of osteosarcoma.

Boldine isolated from Litsea cubeba inhibits bone resorption by suppressing the osteoclast differentiation in collagen-induced arthritis

ObjectiveTo investigate the effect of boldine isolated from Litsea cubeba on collagen-induced arthritis (CIA) rats and explore the molecular mechanism predicted by network pharmacology. Material and methodsCIA rats were orally administered with boldine. The bone destruction of paws was analyzed by histologic examination, tartrate-resistant acid phosphatase (TRACP) staining and micro-computed tomography. Prediction of signal pathway associated with boldine network molecules and CIA genes was applied by the network pharmacology analysis. The expressions of osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK) and its ligand (RANKL) in the ankle were detected by immunohistochemistry. In vitro osteoclasts were cultured in the presence of variable doses of boldine and the RANK expressions were evaluated using Real-time polymerase chain reaction and western blot. ResultsBoldine reduced ankle swelling, alleviated pathological damage and significantly prevented bone destruction in CIA rats. Consistent with this, enzyme linked immunosorbent assay revealed boldine decreased serum TRACP5b levels and osteoclast number in the ankle region by TRACP staining from CIA rats. The network pharmacology analysis indicated that RANK signaling in osteoclasts was the most significant canonical pathway associated with boldine network molecules and CIA genes, which was verified by the increased expression of OPG, reduced expression of RANK, RANKL and RANKL/OPG in boldine-treated CIA rats. The in vitro study further confirmed that boldine inhibited osteoclastogenesis by inhibiting the RANKL/RANK signaling pathway. ConclusionTaken together, our study first indicates that boldine from Litsea cubeba suppresses osteoclastogenesis, improves bone destruction by down-regulating the OPG/RANKL/RANK signal pathway and may be a potential therapeutic agent for rheumatoid arthritis.

MicroRNA-34a alleviates steroid-induced avascular necrosis of femoral head by targeting Tgif2 through OPG/RANK/RANKL signaling pathway.

The study aims to investigate the effect of microRNA-34a (miR-34a) targeting Tgif2 on steroid-induced avascular necrosis of femoral head (SANFH) by regulating OPG/RANK/RANKL signaling pathway. SD rats were divided into normal control and model (RNAKL rat models) groups. The model group was further assigned into model control, negative control, miR-34a mimics and miR-34a inhibitors groups. QRT-PCR was applied to detect miR-34a, Tgif2, OPG, RANK and RNAKL mRNA expressions. Femoral head tissues were collected for Micro-CT scanning and HE staining. QRT-PCR and Western blotting were used to detect expressions of miR-34a, Tgif2, OPG, RANK, RANKL and Runx2, OPN and OC in bone tissues. Dual-luciferase reporter gene assay was used to testify the target relationship between miR-34a and Tgif2. Compared with the normal control group, the model group showed increased Tgif2, RANK and RANKL mRNA expressions, but decreased miR-34a and OPG mRNA expressions. Tgif2 mRNA expression was negatively correlated with miR-34a and OPG mRNA expressions. Micro-CT showed cystic degeneration of femoral head, with decreased bone volume/total volume (BV/TV), bone surface area/bone volume and trabecular number in the model control group compared with the normal control group. Compared with the model control group, the miR-34a mimics group showed increased BV/TV and trabecular thickness and Runx2, OPN and OC expressions, while the parameters decreased in the miR-34a inhibitors group. Compared with the normal control group, the other groups showed increased Tgif2, RANK and RANKL expressions but decreased miR-34a and OPG expressions. Compared with the model control group, Tgif2, RANK and RANKL expressions decreased and miR-34a and OPG expressions increased in the miR-34a mimics group, while the miR-34a inhibitors group had a reverse trend in contrast to the miR-34a mimics group. Tgif2 is a target gene of miR-34a. In conclusion, miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway. Impact statement miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway, which can be used as a new theoretical basis for SANFH treatment.

E6Tensors: A Mathematica package for [formula omitted] Tensors

We present the Mathematica package E6Tensors, a tool for explicit tensor calculations in E6 gauge theories. In addition to matrix expressions for the group generators of E6, it provides structure constants, various higher rank tensors and expressions for the representations 27, 78, 351 and 351′. This paper comes along with a short manual including physically relevant examples. I further give a complete list of gauge invariant, renormalisable terms for superpotentials and Lagrangians. Program summaryProgram Title:E6TensorsProgram Files doi:http://dx.doi.org/10.17632/tk3xtvsd7b.1Licensing provisions: GNU GPLv3Programming language:Wolfram Mathematica 8-10Nature of problem: Group theoretic calculations for E6 GUT Models.Solution method: Direct calculation via explicit expressions.

Effect of naringin on osteoclast differentiation

To discuss the effect of Drynariae Rhizoma's naringin on osteoclasts induced by mouse monocyte RAW264.7. RAW264.7 cells were induced by 100 μg x L(-1) nuclear factor-κB receptor activator ligand (RANKL) and became mature osteoclasts, which were identified through TRAP specific staining and bone resorption. MTT method was sued to screen and inhibit and the highest concentration of osteoclasts. After being cultured with the screened medium containing naringin for 5 days, positive TRAP cell counting and bone absorption area analysis were adopted to observe the effect of naringin on the formation of osteoclast sells and the bone absorption function. The osteoclast proliferation was measured by flow cytometry. The effects of RANK, TRAP, MMP-9, NFATc1 and C-fos mRNA expressions on nuclear factor-κB were detected by RT-PCR. Naringin could inhibit osteoclast differentiation, bone absorption function and proliferation activity of osteoclasts, significantly down-regulate RANK, TRAP, MMP-9 and NFATc1 mRNA expressions in the osteoclast differentiation process, and up-regulate the C-fos mRNA expression. Naringin could inhibit osteoclast differentiation, proliferation and bone absorption function. Its mechanism may be achieved by inhibiting the specific gene expression during the osteoclast differentiation process.

Unexplored Hypotheses on Potency-Magnitude Relations of eWOM Messages with Intensified Comparative Expressions

Electronic word-of-mouth (eWOM) is an important information source that influences consumer product evaluations. The author previously developed a computational model that predicts the potency-magnitude relations of eWOM messages involving subjective rank expressions, which refer to linguistic representations related to the attitude-levels of the benefits of product attributes. This paper extends the typology of message expressions and mathematically investigates potency-magnitude relations with a focus on intensified comparative expressions that involve the “degree” of the differences among two or more objects. The investigations were performed first under the premise of a strict assumption called an interval assumption, and the results were verified under the premise of a conservative assumption called a surjection assumption. These assumptions were introduced to determine the cognitive relationship between attitude-levels and their difference-levels. The investigations include the development of a Q-magnitude Relation Map (Q-Map) that illustrates how the relations change based on the values of two evaluation parameters: evaluation target size and evaluation scale size. Based on the observations of the Q-Maps, five unexplored hypotheses on the potency-magnitude relations were developed with respect to intensified comparative expressions.

Osteoclast progenitor cells present in significant amounts in mouse calvarial osteoblast isolations and osteoclastogenesis increased by BMP-2

Enzymatically released cells from neonatal mouse calvarial bones are frequently used as primary mouse osteoblasts for in vitro studies. We, here, report that although these cells lack mRNA expression of the osteoclastic genes Calcr, Acp5 and Mmp-9 at early time points after their isolation, these transcripts are gradually upregulated when the calvarial osteoblast cultures are differentiated to more mature osteoblasts in long term cultures. Similarly, Calcr, Acp5, Mmp-9, as well as Rank and Nfatc1 mRNA expressions are robustly increased when the osteoblast cultures were induced to differentiate by treatment with bone morphogenetic protein (BMP-2). The increased Calcr mRNA resulted in functionally active calcitonin receptors. Enhanced osteoblastic differentiation was associated with increased Rankl mRNA expression and decreased Opg and Cfs1 mRNA expression. Treatment of the osteoblastic cells with BMP-2 or RANKL, either on plastic dishes or bone slices, resulted in the formation of multinucleated tartrate-resistant acid phosphatase positive cells, which were able to excavate resorption pits and release CTX from the bones. In contrast, increased osteoblastic differentiation induced by BMP-2 in the mouse calvarial osteoblastic cell line MC3T3-E1 was not associated with increased mRNA expression of Calcr, Acp5, Rank, c-Fms or Oscar. Interestingly, Ctsk mRNA was increased during osteoblastic differentiation in both mouse calvarial osteoblast cultures and in MC3T3-E1 cultures. Also osteoblasts isolated from mouse long bones by outgrowth from explant cultures were contaminated with osteoclast progenitors able to differentiate into bone resorbing osteoclasts. These data indicate that mouse calvarial osteoblast cultures contain osteoclast progenitor cells, which will be differentiated along the osteoclastic lineage during osteoblastic differentiation. Moreover, the data show that BMP-2 not only stimulates osteoblastic differentiation but can also induce osteoclastogenesis through increased RANKL.

Computational Approach to Prediction of Attitude Change Through eWOM Messages Involving Subjective Rank Expressions

Electronic word-of-mouth (eWOM) is an impor- tant information source that influences consumer product evaluations. This paper presents a computational model that predicts the potency-magnitude relations of eWOM messages involving subjective rank expressions, which refer to the linguistic representations related to the attitude-levels of the benefits of the product attributes. The amount of required inference for the message receiver to know the attitude-level through the message is quantified as inference quantum by using inference space, which is characterized by two evaluation parameters: evaluation target size and evaluation scale size. The computational model incorporates the idea of inference quantum into the cognitive hypotheses that were developed to account for the potency differences with reference to the expertise levels - experts or novices - of the message receiver of the products. By applying the computational model to simple eWOM messages, the potency-magnitude relations were observed to depend critically on the values of the message receiver's evaluation parameters. This paper defines three message- classes, which are also studied in the areas of opinion mining and sentiment analysis, and investigates mathematically how the potency-magnitude relations change based on the values of the evaluation parameters.

RANK, RANKL and OPG expressions in a permanent molar with a replacement resorption

The aim of this study was to explore the expression of RANK, RANKL and OPG during ankylosis. Structural details and immunohistochemical investigations of the expression of RANK, RANKL and OPG in an extracted secondary retained permanent molar of a 12-year-old girl are reported. Woven and lamellar bones were observed in the thickness of the remodeled dental wall and a tertiary dentin was noticed around the pulp cavity. The resorbing multinucleated cells expressed TRAP and RANK but few of them also expressed RANKL. Both odontoblasts and osteoblasts expressed TRAP and RANK, but the expression of RANKL was limited to osteoblasts. OPG remained undetected. The present case reveals unusual expression of RANKL in the resorbing cells, TRAP and RANK in both osteoblasts and odontoblasts, and a failure of detection of OPG. These proteins could be involved in the pathogenesis of tooth ankylosis.

Effects of osthole, psoralen, aconitine on breast cancer MDA-MB-231BO cell line inhibition in vitro

To explore the inhibitory effects and to investigate the mechanisms of combined treatment of osthole, psoralen with aconitine on human breast cancer cell line MDA-MB-231BO. The best inhibitory concentration of osthole, psoralen combined with aconitine on MDA-MB-231BO cells was obtained by stepwise regression analysis after adopting a uniform experiment design. The invasive activities were observed by transwell assays, and expressions of transforming growth factor-β1 (TGF-β1), Smad2, Smad3, Smad4, Smad7, nuclear factor-κB (NF-κB) and receptor activator of NF-κB ligand (RANK) mRNAs were analyzed by real-time quantitative polymerase chain reaction. The optimal combination concentrations of osthol, psoralen and aconitine were 6.44, 8.89 and 9.44 μg/mL, respectively. Cell invasion was significantly inhibited after 24 hours of treatment using the combination drugs and zoledronic acid. TGF-β1, Smad2, Smad3, Smad4, Smad7, NF-κB and RANK mRNA expressions of the optimal combination group and zoledronic acid group were significantly reduced compared with the control group (P<0.01). Furthermore, TGF-β1, Smad2, Smad3, Smad4, Smad7, NF-κB and RANK mRNA expressions of the optimal combination group were significantly lower than those of the weak combination group (P<0.01). Combination treatment of osthole, psoralen with aconitine can inhibit cancer cell invasion, which is a result of alteration of the TGF-β/Smad signaling pathway and down-regulation of NF-κB and RANK expressions.

Osteoprotegerin/RANK/RANKL axis in cardiac remodeling due to immuno-inflammatory myocardial disease

Objective Osteoprotegerin (OPG) and the receptor activator of nuclear factor-κB ligand (RANKL) are inflammatory cytokines traditionally linked to the regulation of bone remodeling. We hypothesize that the OPG/RANK/RANKL axis may be involved in extracellular matrix remodeling in immuno-inflammatory heart diseases, and explore the probable underlying mechanisms by using anti-IL-17 in the model of experimental autoimmune myocarditis. Methods EAM was induced in Lewis rats by injection of porcine cardiac myosin. All the rats were randomly distributed into day 0, day 7, day 14 and day 28 groups, which means rats in certain group were cervical dislocated on day 0, day 7, day 14 and day 28 respectively. HE staining and Masson's staining were used for measurement of cardiac hypertrophy and interstitial fibrosis. Hydroxyproline content and collagen cross-linking were determined in heart section. Anti-IL-17 or control antibody was injected i.p. 2 h before and 3 days and 7 days after the first myosin immunization in EAM model, that is, group anti-IL-17 or group control antibody. IL-17 and OPG/RANK/RANKL axis expressions were detected by realtime RT-PCR in all the six groups. In the in vitro studies, cardiac fibroblasts were cultured and treated with IL-17 or vehicle for 48 h. Total RNA was isolated from harvested cells and realtime RT-PCR was performed to detect the RANK, RANKL, OPG and MMP-2, MMP-9, TIMP-1 and TIMP-2 expressions, then matrix metalloproteinase activity was assayed. Results Our in vivo results revealed that expression of IL-17 and the OPG/RANK/RANKL axis increased significantly from day 0 to day 28, with IL-17 and OPG increased relatively steeply. In the in vitro study, we detected OPG, RANK and RANKL mRNA expressions in the cultured fibroblasts with or without IL-17 stimulation. We found that IL-17 increased the OPG/RANK/RANKL axis activity ( P < 0.05). Although IL-17 induced a significant increase in MMP-2 and MMP-9 gene expressions in cardiac fibroblasts, there was no change in TIMP-2 and TIMP-1 expressions. Conclusions Our results suggest that the OPG/RANK/RANKL axis may be involved in cardiac remodeling in immuno-inflammatory myocardial diseases and progression of chronic HF and thus may represent targets for intervention in this disorder.

Kinetics of RANKL, RANK and OPG expressions in experimentally induced rat periapical lesions

The object of this study was to elucidate the kinetics of receptor activator of NFkB ligand (RANKL), RANK, osteoprotegerin (OPG), and cytokine expressions in experimentally induced rat periapical lesions. The mRNA expressions of RANKL, RANK, OPG, and cytokines in experimentally induced rat periapical lesions were evaluated by real-time PCR. The lesions were induced in male Wistar rats (n = 48, 5 weeks of age) by unsealed pulp exposure of the lower first molars. Expression of RANKL was up-regulated at the beginning of lesion expansion, and expression ratio of RANKL against OPG, a competitor of RANKL, peaked at 2 and 3 weeks. Expression of inflammatory cytokines, such as TNF-alpha, IL-1alpha, and IL-1beta also increased at this stage, suggesting contribution of synergic effects of RANKL and proinflammatory cytokine signaling to lesion expansion. Most of RANKL+ cells were fibroblastic, but few of them were T cells. Expression of RANKL and proinflammatory cytokines was correlated with periapical lesion expansion.