Retracted: Topical Treatment with Xiaozheng Zhitong Paste (XZP) Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling.
Ontology highlight
ABSTRACT:
SUBMITTER: And Alternative Medicine EC
PROVIDER: S-EPMC7769638 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Retracted: Topical Treatment with Xiaozheng Zhitong Paste (XZP) Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling.
And Alternative Medicine Evidence-Based Complementary EC
Evidence-based complementary and alternative medicine : eCAM 20201218
[This retracts the article DOI: 10.1155/2015/215892.]. ...[more]
Similar Datasets
Project description:Bones as an alive organ consist of about 70% mineral and 30% organic component. About 200 million people are suffering from osteopenia and osteoporosis around the world. There are multiple ways of protecting bone from endogenous and exogenous risk factors. Planned physical activity is another useful way for protecting bone health. It has been investigated that arranged exercise would effectively regulate bone metabolism. Until now, a number of systems have discovered how exercise could help bone health. Previous studies reported different mechanisms of the effect of exercise on bone health by modulation of bone remodeling. However, the regulation of RANKL/RANK/OPG pathway in exercise and physical performance as one of the most important remodeling systems is not considered comprehensive in previous evidence. Therefore, the aim of this review is to clarify exercise influence on bone modeling and remodeling, with a concentration on its role in regulating RANKL/RANK/OPG pathway.
| S-EPMC7053481 | biostudies-literature
Project description:RANKL/RANK/OPG system consists of three essential signaling molecules: i) the receptor activator of nuclear factor (NF)-kB-ligand (RANKL), ii) the receptor activator of NF-kB (RANK), and iii) the soluble decoy receptor osteoprotegerin (OPG). Although this system is critical for the regulation of osteoclast differentiation/activation and calcium release from the skeleton, different studies have elucidated its specific role in mammary gland physiology and hormone-driven epithelial proliferation during pregnancy. Of note, several data suggest that progesterone induces mammary RANKL expression in mice and humans. In turn, RANKL controls cell proliferation in breast epithelium under physiological conditions typically associated with higher serum progesterone levels, such as luteal phase of the menstrual cycle and pregnancy. Hence, RANKL/RANK system can be regarded as a major downstream mediator of progesterone-driven mammary epithelial cells proliferation, potentially contributing to breast cancer initiation and progression. Expression of RANKL, RANK, and OPG has been detected in breast cancer cell lines and in human primary breast cancers. To date, dysregulation of RANKL/RANK/OPG system at the skeletal level has been widely documented in the context of metastatic bone disease. In fact, RANKL inhibition through the RANKL-blocking human monoclonal antibody denosumab represents a well-established therapeutic option to prevent skeletal-related events in metastatic bone disease and adjuvant therapy-induced bone loss in breast cancer. On the other hand, the exact role of OPG in breast tumorigenesis is still unclear. This review focuses on molecular mechanisms linking RANKL/RANK/OPG system to mammary tumorigenesis, highlighting pre-clinical and clinical evidence for the potential efficacy of RANKL inhibition as a prevention strategy and adjuvant therapy in breast cancer settings.
| S-EPMC6325760 | biostudies-literature
Project description:AIM: Lactoferrin (LF), an 80-kDa iron-binding glycoprotein, is a pleiotropic factor found in colostrum, milk, saliva and epithelial cells of the exocrine glands. The aim of this study was to evaluate the effects of LF on the bones in ovariectomized (Ovx) rats and to identify the pathways that mediate the anabolic action of LF on the bones. METHODS: Female Sprague-Dawley rats (6-month-old) underwent ovariectomy, and were treated with different doses of LF (10, 100, 1000, and 2000 mg·kg(-1)·d(-1), po) or with 7β-estradiol (0.1 mg·kg(-1), im, each week) as the positive control. By the end of 6 month-treatments, the bone mass and microstructure in the rats were scanned by micro-computed tomography (micro-CT), and the bone metabolism was evaluated with specific markers, and the mRNA levels of osteoprotegerin (OPG) and the receptor-activator of nuclear factor κB ligand (RANKL) in femur were measured using qRT-PCR. RESULTS: LF treatment dose-dependently elevated the bone volume (BV/TV), trabecular thickness (TbTh) and trabecular number (TbN), and reduced the trabecular separation (TbSp) in Ovx rats. Furthermore, higher doses of LF (1000 and 2000 mg·kg(-1)·d(-1)) significantly increased the bone mineral density (BMD) compared with the untreated Ovx rats. The higher doses of LF also significantly increased the serum levels of OC and BALP, and decreased the serum levels of β-CTx and NTX. LF treatment significantly increased the OPG mRNA levels, and suppressed the RANKL mRNA levels, and the RANKL/OPG mRNA ratio in Ovx rats. CONCLUSION: Oral administration of LF preserves the bone mass and improves the bone microarchitecture. LF enhances bone formation, reduces bone resorption, and decreases bone mass loss, possibly through the regulation of OPG/RANKL/RANK pathway.
| S-EPMC4002710 | biostudies-other
Project description:RANKL and RANK are expressed in different cell types and tissues throughout the body. They were originally described for their essential roles in bone remodeling and the immune system but have subsequently been shown to provide essential signals from regulating mammary gland homeostasis during pregnancy to modulating tumorigenesis. The success of RANKL/RANK research serves as a paragon for translational research from the laboratory to the bedside. The case in point has been the development of Denosumab, a RANKL-blocking monoclonal antibody which has already helped millions of patients suffering from post-menopausal osteoporosis and skeletal related events in cancer. Here we will provide an overview of the pathway from its origins to its clinical relevance in disease, with a special focus on emerging evidence demonstrating the therapeutic value of targeting the RANKL/RANK/OPG axis not only in breast cancer but also as an addition to the cancer immunotherapy arsenal.
| S-EPMC7426519 | biostudies-literature
Project description:PurposeDiabetic foot is a complication of long-lasting diabetes mellitus affecting up to 15% of patients, both in type 1 and type 2 diabetes. Osteoprotegerin is involved in osteogenesis and calcification. The aim of the study was to assess the role of selected osteoprotegerin gene variants in diabetes patients with diabetic foot.MethodsThe study involved 300 patients with diabetes and diabetic foot and 968 healthy controls. The study group was formed by 243 patients with diabetic foot of neuropathic origin, 102 with diabetic foot of neuroischemic origin and 77 with Charcot neuroarthropathy.ResultsCompared to controls, rs1872426 and rs1485286 showed correlation with diabetic foot in diabetes subjects. Significant associations between rs2073618, rs1872426, rs7464496 and rs1485286 in men were reported. The aforementioned correlations were also present in type 2 diabetes patient subgroup. Variant rs1485286 was associated to diabetic foot of neuropathic origin. Sex-specificity for females was present for rs6993813 in patients with diabetic foot of neuropathic origin and type 1 diabetes. Variants rs1872426, rs2073617 and rs1485286 were correlated with CN. We found that age, body weight, body mass index, waist circumference, hip circumference and waist-hip ratio were among the basic risk factors of diabetic foot.ConclusionsThe following variants TNFRSF11B (rs2073618, rs2073617, rs1872426, rs1032128, rs7464496, rs11573829 and rs1485286), COLEC10 (rs6993813, rs3134069) and TNFSF11 (rs9533156) present differences in allele frequencies in diabetic foot patients and show correlation with gender, diabetes type and diabetic foot etiology.
| S-EPMC6405386 | biostudies-literature
Project description:Periodontitis is based on a complex inflammatory over-response combined with possible genetic predisposition factors. The RANKL/RANK/OPG signaling pathway is implicated in bone resorption through its key function in osteoclast differentiation and activation, as well as in the inflammatory response. This central element of osteo-immunology has been suggested to be perturbed in several diseases, including periodontitis, as it is a predisposing factor for this disease. The aim of the present study was to validate this hypothesis using a transgenic mouse line, which over-expresses RANK (RTg) and develops a periodontitis-like phenotype at 5 months of age. RTg mice exhibited severe alveolar bone loss, an increased number of TRAP positive cells, and disorganization of periodontal ligaments. This phenotype was more pronounced in females. We also observed dental root resorption lacunas. Hyperplasia of the gingival epithelium, including Malassez epithelial rests, was visible as early as 25 days, preceding any other symptoms. These results demonstrate that perturbations of the RANKL/RANK/OPG system constitute a core element of periodontitis, and more globally, osteo-immune diseases.
| S-EPMC5442248 | biostudies-literature
Project description:In women, malignant breast tumours are among the most common malignant diseases in Europe. In advanced breast cancer, the risk of bone metastasis increases to 65-75?%. The discovery of the physiological bone metabolism parameters RANK (receptor activator of nuclear factor-?B), RANKL (receptor activator of nuclear factor-?B ligand) and OPG (osteoprotegerin) as well as their pathophysiological involvement in bone-related diseases is the subject of new therapeutic strategies. The formation of osteolytic bone metastasis requires increased osteoclast activity. Activation of osteoclasts by excessive direct RANKL or reduced OPG expression of osseous metastatic tumour cells remains to be elucidated. More than 50?% of primary breast cancer cells express OPG and RANK, while RANKL could be detected only in 14-60?%. Increased OPG concentrations in the serum of patients with bone metastases have been shown in several studies, whereas the RANKL results are described in an opposite manner. The use of OPG as a biomarker for the detection of osteolytic bone metastases is not consistent and needs to be proved in further studies. Increased RANKL activity was found in diseases characterised by excessive bone loss and formed the basis of new therapeutic options. In several studies, a human monoclonal antibody to RANKL (denosumab) was investigated for the treatment of bone diseases. Denosumab is a promising therapeutic option due to its bone-protective effects.
| S-EPMC4168338 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is closely associated with periarticular osteopenia and leads to a high risk of generalized osteoporosis. Although glucocorticoid (GC) treatment ameliorates joint degradation and manages inflammation in RA, GC application may induce further bone quality deterioration in RA patients. Current treatments for RA lack relevant strategies for the prevention and treatment of osteopenia in RA. In this study, we aimed to investigate whether salvianolate treatment ameliorated osteopenia in prednisone-treated RA rats. Lewis rats with collagen-induced arthritis (CIA) were administered prednisone (PDN) or PDN plus salvianolate (PDN+Sal) treatment for 90 days. The effects of Sal were investigated in PDN-treated CIA rats. To further evaluate the effects of Sal under inflammatory conditions, we investigated the effects of Sal treatment on the TNF-α-induced inflammatory response in MC3T3-E1 osteoblasts. Bone histomorphometry, bone mineral density (BMD), bone biomechanical properties, micro-computed tomography (micro-CT), immunohistochemistry, RT-PCR and western blot analyses were performed to evaluate the effects of Sal. The results demonstrated that RA induced bone loss and bone quality deterioration, with high bone turnover in CIA rats. PDN+Sal treatment significantly increased BMD and trabecular/cortical bone mass, suppressed inflammation, and improved bone biomechanical properties compared to CIA control and PDN treatment. PDN+Sal treatment significantly suppressed bone resorption and the RANKL and RANKL/OPG ratios compared to PDN. PDN+Sal and PDN treatment significantly inhibited TNF-α by 82 and 83%, respectively, and both suppressed inflammation in CIA rats. However, there was no significant difference between PDN+Sal and PDN treatment alone in regard to bone formation parameters or the management of inflammation and arthropathy. Sal significantly increased Osterix, OPN, and Col1a1 while decreasing RANKL, TRAF6, and TRAIL gene in TNF-α-induced MC3T3-E1 osteoblasts. Sal significantly increased Osterix, OPN and RUNX2 while decreasing NF-κB, TRAF6 and IL-1β protein in TNF-α-induced MC3T3-E1 osteoblasts. The results suggested that salvianolate treatment ameliorated osteopenia and improved bone quality in prednisone-treated RA rats, and the potential mechanism may be related to the regulation of the RANKL/RANK/OPG signaling pathway, TRAIL-TRAF6-NFκB signal axis, and downregulation of inflammatory cytokines. Salvianolate could be used as a promising supplemental therapeutic strategy to ameliorate osteopenia and improve bone quality in GC-treated RA patients.
| S-EPMC8450458 | biostudies-literature
Project description:Together with its dominant immunological and bone remodeling involvement, RRO axis, comprising of receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) signaling, is as well-implicated in CNS functioning and corresponding pathologies. The CNS aspects of RANKL/RANK/OPG (RRO) axis were systematically reviewed. With search 10 databases, and 7 additional resources from first article publication to July 2019, resulted in total 2,222 hits, from which 33 relevant articles were selected. The elements of RRO axis in CNS include cells involved in neuroinflammation, predominantly in microglia, but as well in resident macrophages and inflammatory cells migrating across the blood-brain barrier. The expression in neurons and oligodendrocytes is mainly confined to processes of differentiation and cell death. RRO axis tunes the neuroinflammatory response, depending on the molecular, cellular and pathological context. RANK/RANKL signaling is neuroprotective in TLR-mediated inflammation, while OPG seems detrimental in stroke, but beneficial in multiple sclerosis. The levels of RRO axis elements can serve as biomarkers in the blood and cerebrospinal fluid. They act as neuroprotectant after brain damage even being implicated in body weight- and thermo-regulation. As derivatives of RRO axis already exist as therapeutic agents in bone remodeling, it would be intriquing to see if these or new RRO-based pharmaceuticals would appear effective in CNS therapies.
| S-EPMC7710989 | biostudies-literature
Project description:We sought to determine the influence of single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG on volumetric bone mineral density (vBMD) and bone geometry at the radius in men. Pairwise tag SNPs (r (2) ? 0.8) for RANKL (n = 8), RANK (n = 44), and OPG (n = 22) and five SNPs near RANKL and OPG strongly associated with areal BMD in genomewide association studies were previously genotyped in men aged 40-79 years in the European Male Ageing Study (EMAS). Here, these SNPs were analyzed in a subsample of men (n = 589) who had peripheral quantitative computed tomography (pQCT) performed at the distal (4%) and mid-shaft (50%) radius. Estimated parameters were total and trabecular vBMD (mg/mm(3)) and cross-sectional area (mm(2)) at the 4% site and cortical vBMD (mg/mm(3)); total, cortical, and medullary area (mm(2)); cortical thickness (mm); and stress strain index (SSI) (mm(3)) at the 50% site. We identified 12 OPG SNPs associated with vBMD and/or geometric parameters, including rs10505348 associated with total vBMD (? [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (? [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (? [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (? [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (? [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (? [95% CI] = -0.08 [-0.13 to -0.03], P = 0.001). Three RANK SNPs were associated with vBMD, including rs12956925 associated with trabecular vBMD (? [95% CI] = -7.58 [-14.01 to -1.15], P = 0.021). There were five RANK SNPs associated with geometric parameters, including rs8083511 associated with distal radius cross-sectional area (? [95% CI] = 8.90 [0.92-16.88], P = 0.029). No significant association was observed between RANKL SNPs and pQCT parameters. Our findings suggest that genetic variation in OPG and RANK influences radius vBMD and geometry in men.
| S-EPMC3215872 | biostudies-literature