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Abstract Osteoarthritis (OA) is characterized by the infiltration of a number of proinflammatory cytokines into the joint microenvironment. Betulin is a natural analogue of betulinic acid, a lupane-type pentacyclic triterpene that... more
Abstract Osteoarthritis (OA) is characterized by the infiltration of a number of proinflammatory cytokines into the joint microenvironment. Betulin is a natural analogue of betulinic acid, a lupane-type pentacyclic triterpene that displays many important biological activities, including anti-inflammatory activity, although the effects on inflammatory cytokine production in OA are unknown. Analyses of samples from the Gene Expression Omnibus (GEO) dataset and our own clinical samples revealed higher levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) in OA synovial tissue compared with normal healthy tissue. This was also the case in synovial tissue from normal healthy rats and rats subjected to anterior cruciate ligament transaction (ACLT)-induced OA. High-throughput screening of inflammatory cytokines in betulin-treated OA synovial fibroblasts (OASFs) identified TNF-α and IL-1β as potential targets of betulin. Further analyses found that betulin suppresses TNF-α and IL-1β production in OASFs by inhibiting mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase (ERK) and nuclear factor kappa B (NF-κB) signaling cascades. Betulin shows promise for the treatment of OA.
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Research Interests:
Abstract Osteoarthritis (OA) is characterized by the infiltration of a number of proinflammatory cytokines into the joint microenvironment. Betulin is a natural analogue of betulinic acid, a lupane-type pentacyclic triterpene that... more
Abstract Osteoarthritis (OA) is characterized by the infiltration of a number of proinflammatory cytokines into the joint microenvironment. Betulin is a natural analogue of betulinic acid, a lupane-type pentacyclic triterpene that displays many important biological activities, including anti-inflammatory activity, although the effects on inflammatory cytokine production in OA are unknown. Analyses of samples from the Gene Expression Omnibus (GEO) dataset and our own clinical samples revealed higher levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) in OA synovial tissue compared with normal healthy tissue. This was also the case in synovial tissue from normal healthy rats and rats subjected to anterior cruciate ligament transaction (ACLT)-induced OA. High-throughput screening of inflammatory cytokines in betulin-treated OA synovial fibroblasts (OASFs) identified TNF-α and IL-1β as potential targets of betulin. Further analyses found that betulin suppresses TNF-α and IL-1β production in OASFs by inhibiting mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase (ERK) and nuclear factor kappa B (NF-κB) signaling cascades. Betulin shows promise for the treatment of OA.
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Cancer-related bone erosion occurs frequently in bone metastasis and is associated with severe complications such as chronic bone pain, fractures, and lower survival rates. In recognition of the fact that the darkness hormone melatonin is... more
Cancer-related bone erosion occurs frequently in bone metastasis and is associated with severe complications such as chronic bone pain, fractures, and lower survival rates. In recognition of the fact that the darkness hormone melatonin is capable of regulating bone homeostasis, we explored its therapeutic potential in bone metastasis. We found that melatonin directly reduces osteoclast differentiation, bone resorption activity and promotes apoptosis of mature osteoclasts. We also observed that melatonin inhibits RANKL production in lung and prostate cancer cells by downregulating the p38 MAPK pathway, which in turn prevents cancer-associated osteoclast differentiation. In lung and prostate bone metastasis models, twice-weekly melatonin treatment markedly reduced tumor volumes and numbers of osteolytic lesions. Melatonin also substantially lowered the numbers of TRAP-positive osteoclasts in tibia bone marrow and RANKL expression in tumor tissue. These findings show promise for melatonin in the treatment of bone metastases.
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Cancer-related bone erosion occurs frequently in bone metastasis and is associated with severe complications such as chronic bone pain, fractures, and lower survival rates. In recognition of the fact that the darkness hormone melatonin is... more
Cancer-related bone erosion occurs frequently in bone metastasis and is associated with severe complications such as chronic bone pain, fractures, and lower survival rates. In recognition of the fact that the darkness hormone melatonin is capable of regulating bone homeostasis, we explored its therapeutic potential in bone metastasis. We found that melatonin directly reduces osteoclast differentiation, bone resorption activity and promotes apoptosis of mature osteoclasts. We also observed that melatonin inhibits RANKL production in lung and prostate cancer cells by downregulating the p38 MAPK pathway, which in turn prevents cancer-associated osteoclast differentiation. In lung and prostate bone metastasis models, twice-weekly melatonin treatment markedly reduced tumor volumes and numbers of osteolytic lesions. Melatonin also substantially lowered the numbers of TRAP-positive osteoclasts in tibia bone marrow and RANKL expression in tumor tissue. These findings show promise for melatonin in the treatment of bone metastases.
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Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks synovial joint tissues. Interleukin (IL)‐1β is a critical proinflammatory cytokine in RA progression. Sphingosine‐1‐phosphate... more
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks synovial joint tissues. Interleukin (IL)‐1β is a critical proinflammatory cytokine in RA progression. Sphingosine‐1‐phosphate (S1P), a platelet‐derived lysophospholipid mediator, reportedly regulates osteoimmunology. Here, we investigated how S1P mediates IL‐1β expression in osteoblasts. Our analysis of records from the Gene Expression Omnibus (GEO) database demonstrate higher levels of IL‐1β in patients with RA compared with those with osteoarthritis. Stimulation of osteoblasts with S1P concentration dependently increased mRNA and protein expression of IL‐1β. Elevations in IL‐1β mRNA expression induced by S1P were reduced by the small interfering RNA (siRNA) against the S1P1 receptor. S1P also augmented JAK and STAT3 molecular cascades. We also found that JAK and STAT3 inhibitors and their siRNAs antagonized S1P‐promoted IL‐1β expression. Our results indicate that S1P promote...
Research Interests:
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks synovial joint tissues. Interleukin (IL)‐1β is a critical proinflammatory cytokine in RA progression. Sphingosine‐1‐phosphate... more
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks synovial joint tissues. Interleukin (IL)‐1β is a critical proinflammatory cytokine in RA progression. Sphingosine‐1‐phosphate (S1P), a platelet‐derived lysophospholipid mediator, reportedly regulates osteoimmunology. Here, we investigated how S1P mediates IL‐1β expression in osteoblasts. Our analysis of records from the Gene Expression Omnibus (GEO) database demonstrate higher levels of IL‐1β in patients with RA compared with those with osteoarthritis. Stimulation of osteoblasts with S1P concentration dependently increased mRNA and protein expression of IL‐1β. Elevations in IL‐1β mRNA expression induced by S1P were reduced by the small interfering RNA (siRNA) against the S1P1 receptor. S1P also augmented JAK and STAT3 molecular cascades. We also found that JAK and STAT3 inhibitors and their siRNAs antagonized S1P‐promoted IL‐1β expression. Our results indicate that S1P promote...
Research Interests:
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks synovial joint tissues. Interleukin (IL)‐1β is a critical proinflammatory cytokine in RA progression. Sphingosine‐1‐phosphate... more
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks synovial joint tissues. Interleukin (IL)‐1β is a critical proinflammatory cytokine in RA progression. Sphingosine‐1‐phosphate (S1P), a platelet‐derived lysophospholipid mediator, reportedly regulates osteoimmunology. Here, we investigated how S1P mediates IL‐1β expression in osteoblasts. Our analysis of records from the Gene Expression Omnibus (GEO) database demonstrate higher levels of IL‐1β in patients with RA compared with those with osteoarthritis. Stimulation of osteoblasts with S1P concentration dependently increased mRNA and protein expression of IL‐1β. Elevations in IL‐1β mRNA expression induced by S1P were reduced by the small interfering RNA (siRNA) against the S1P1 receptor. S1P also augmented JAK and STAT3 molecular cascades. We also found that JAK and STAT3 inhibitors and their siRNAs antagonized S1P‐promoted IL‐1β expression. Our results indicate that S1P promote...
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Background: Sympathetic activity, including cervical ganglia, is involved in the development of cardiac arrhythmias. Objective: The present study investigated the association between cervical spondylosis and arrhythmia, which has never... more
Background: Sympathetic activity, including cervical ganglia, is involved in the development of cardiac arrhythmias. Objective: The present study investigated the association between cervical spondylosis and arrhythmia, which has never been reported before. Methods: Patients newly diagnosed with cervical spondylosis (CS) with an index date between 2000 and 2011 were identified from the National Health Insurance Research Database. We performed a 1:1 case-control matched analysis. Cases were matched to controls according to their estimated propensity scores, based on demographics and existing risk factors. Cox proportional hazard models were applied to assess the association between CS and arrhythmia. Results: The CS cohort comprised 22,236 patients (males, 42.6%; mean age, 54.4 years) and non-CS cohort comprised 22,236 matched controls. There were 1441 events of arrhythmia in CS cohort and 537 events of arrhythmia in non-CS cohort, which 252 and 127 events of atrial fibrillation in C...
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Background: Sympathetic activity, including cervical ganglia, is involved in the development of cardiac arrhythmias. Objective: The present study investigated the association between cervical spondylosis and arrhythmia, which has never... more
Background: Sympathetic activity, including cervical ganglia, is involved in the development of cardiac arrhythmias. Objective: The present study investigated the association between cervical spondylosis and arrhythmia, which has never been reported before. Methods: Patients newly diagnosed with cervical spondylosis (CS) with an index date between 2000 and 2011 were identified from the National Health Insurance Research Database. We performed a 1:1 case-control matched analysis. Cases were matched to controls according to their estimated propensity scores, based on demographics and existing risk factors. Cox proportional hazard models were applied to assess the association between CS and arrhythmia. Results: The CS cohort comprised 22,236 patients (males, 42.6%; mean age, 54.4 years) and non-CS cohort comprised 22,236 matched controls. There were 1441 events of arrhythmia in CS cohort and 537 events of arrhythmia in non-CS cohort, which 252 and 127 events of atrial fibrillation in C...
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The hormone melatonin has many properties, including antioxidant, anti‐inflammatory, and immunomodulatory effects. Melatonin has been demonstrated to be beneficial in several inflammatory autoimmune diseases, but its effects in rheumatoid... more
The hormone melatonin has many properties, including antioxidant, anti‐inflammatory, and immunomodulatory effects. Melatonin has been demonstrated to be beneficial in several inflammatory autoimmune diseases, but its effects in rheumatoid arthritis (RA) remain controversial. We sought to determine how melatonin regulates inflammation in RA. We found that melatonin dose‐dependently inhibits tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐1β expression through the PI3K/AKT, ERK, and NF‐κB signaling pathways. We also identified that melatonin inhibits TNF‐α and IL‐1β production by upregulating miR‐3150a‐3p expression. Synovial tissue specimens from RA patients and culture of human rheumatoid fibroblast‐like synoviocytes confirmed that the MT1 receptor is needed for the anti‐inflammatory activities of melatonin. Importantly, melatonin also significantly reduced paw swelling, cartilage degradation, and bone erosion in the collagen‐induced arthritis mouse model. Our results indicate ...
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The hormone melatonin has many properties, including antioxidant, anti‐inflammatory, and immunomodulatory effects. Melatonin has been demonstrated to be beneficial in several inflammatory autoimmune diseases, but its effects in rheumatoid... more
The hormone melatonin has many properties, including antioxidant, anti‐inflammatory, and immunomodulatory effects. Melatonin has been demonstrated to be beneficial in several inflammatory autoimmune diseases, but its effects in rheumatoid arthritis (RA) remain controversial. We sought to determine how melatonin regulates inflammation in RA. We found that melatonin dose‐dependently inhibits tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐1β expression through the PI3K/AKT, ERK, and NF‐κB signaling pathways. We also identified that melatonin inhibits TNF‐α and IL‐1β production by upregulating miR‐3150a‐3p expression. Synovial tissue specimens from RA patients and culture of human rheumatoid fibroblast‐like synoviocytes confirmed that the MT1 receptor is needed for the anti‐inflammatory activities of melatonin. Importantly, melatonin also significantly reduced paw swelling, cartilage degradation, and bone erosion in the collagen‐induced arthritis mouse model. Our results indicate ...
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Research Interests: MicroRNA, Metastasis, Cancer Research, Medicine, AMPK, and 2 moreResistin and Chondrosarcoma(Resistin and Chondrosarcoma)
(Resistin and Chondrosarcoma)
Research Interests: MicroRNA, Metastasis, Cancer Research, Medicine, AMPK, and 2 moreResistin and Chondrosarcoma(Resistin and Chondrosarcoma)
(Resistin and Chondrosarcoma)
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ObjectiveThe β-nitrostyrene family has been reported to possess anticancer properties. However, the anticancer activity of β-nitrostyrenes on cervical cancer cells and the underlying mechanisms involved remain unexplored. In this study, a... more
ObjectiveThe β-nitrostyrene family has been reported to possess anticancer properties. However, the anticancer activity of β-nitrostyrenes on cervical cancer cells and the underlying mechanisms involved remain unexplored. In this study, a β-nitrostyrene derivative CYT-Rx20 (3′-hydroxy-4′-methoxy-β-methyl-β-nitrostyrene) was synthesized, and its anticancer activity on cervical cancer cells and the mechanisms involved were investigated.MethodsThe effect of CYT-Rx20 on human cervical cancer cell growth was evaluated using cell viability assay. Reactive oxygen species (ROS) generation and annexin V staining were detected by flow cytometry. The protein expression levels of cleaved caspase-3, cleaved caspase-9, cleaved poly (ADPribose) polymerase, γH2AX, β-catenin, Vimentin, and Twist were measured by Western blotting. DNA double-strand breaks were determined by γ-H2AX foci formation and neutral comet assay. Migration assay was used to determine cancer cell migration. Nude mice xenograft ...
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ObjectiveThe β-nitrostyrene family has been reported to possess anticancer properties. However, the anticancer activity of β-nitrostyrenes on cervical cancer cells and the underlying mechanisms involved remain unexplored. In this study, a... more
ObjectiveThe β-nitrostyrene family has been reported to possess anticancer properties. However, the anticancer activity of β-nitrostyrenes on cervical cancer cells and the underlying mechanisms involved remain unexplored. In this study, a β-nitrostyrene derivative CYT-Rx20 (3′-hydroxy-4′-methoxy-β-methyl-β-nitrostyrene) was synthesized, and its anticancer activity on cervical cancer cells and the mechanisms involved were investigated.MethodsThe effect of CYT-Rx20 on human cervical cancer cell growth was evaluated using cell viability assay. Reactive oxygen species (ROS) generation and annexin V staining were detected by flow cytometry. The protein expression levels of cleaved caspase-3, cleaved caspase-9, cleaved poly (ADPribose) polymerase, γH2AX, β-catenin, Vimentin, and Twist were measured by Western blotting. DNA double-strand breaks were determined by γ-H2AX foci formation and neutral comet assay. Migration assay was used to determine cancer cell migration. Nude mice xenograft ...
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Research Interests: Dentistry, Molecular Biology, Flow Cytometry, Immunohistochemistry, Mitochondria, and 15 moreApoptosis, Medicine, Reactive Oxygen Species, Mice, Animals, Male, Cytochrome C, Glutathione, Clinical Sciences, Mouth Neoplasms, Analysis of Variance, Cell Proliferation, Sensitivity and Specificity, Antineoplastic Agents, and Immunoblotting
Research Interests: Dentistry, Molecular Biology, Flow Cytometry, Immunohistochemistry, Mitochondria, and 15 moreApoptosis, Medicine, Reactive Oxygen Species, Mice, Animals, Male, Cytochrome C, Glutathione, Clinical Sciences, Mouth Neoplasms, Analysis of Variance, Cell Proliferation, Sensitivity and Specificity, Antineoplastic Agents, and Immunoblotting
The β-nitrostyrene family has been shown to suppress cell proliferation and induce apoptosis in types of various cancers. However, the mechanisms underlying the anticancer effects of β-nitrostyrenes in colorectal cancer remain poorly... more
The β-nitrostyrene family has been shown to suppress cell proliferation and induce apoptosis in types of various cancers. However, the mechanisms underlying the anticancer effects of β-nitrostyrenes in colorectal cancer remain poorly understood. In this study, we synthesized a β-nitrostyrene derivative, CYT-Rx20 (3'-hydroxy-4'-methoxy-β-methyl-β-nitrostyrene), and investigated its anticancer activities in human colorectal cancer cells both in vitro and in vivo. Our findings showed that treatment with CYT-Rx20 reduced cell viability and induced DNA damage in colorectal cancer cells. In addition, CYT-Rx20 induced cell cycle arrest of colorectal cancer cells at the G2/M phase and upregulated the protein expression of phospho-ERK, cyclin B1, phospho-cdc2 (Tyr15), aurora A, and aurora B, while it downregulated the expression of cdc25A and cdc25C. Furthermore, we found that CYT-Rx20 caused accumulation of intracellular reactive oxygen species (ROS) and reduction of mitochondrial m...
Research Interests: Flow Cytometry, Immunohistochemistry, Cancer Research, DNA damage, Apoptosis, and 15 moreMedicine, Humans, Reactive Oxygen Species, Mice, Female, Animals, Comet Assay, Carcinogenesis, Cell cycle checkpoints, Cell Proliferation, Antineoplastic Agents, Biochemistry and cell biology, Immunoblotting, Colorectal Neoplasms, and Pharmacology and pharmaceutical sciences
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Osteopontin (OPN) is an important proinflammatory cytokine in rheumatoid arthritis (RA). Levels of OPN have been shown to be significantly correlated with interleukin-17 (IL-17) production and expression of Th17 cells in the synovial... more
Osteopontin (OPN) is an important proinflammatory cytokine in rheumatoid arthritis (RA). Levels of OPN have been shown to be significantly correlated with interleukin-17 (IL-17) production and expression of Th17 cells in the synovial fluid of RA patients. Here, we investigated the role of OPN in monocyte migration, IL-17 production and osteoblasts. OPN and IL-17 expression profiles in osteoarthritis (OA) and RA synovial fluid were determined by enzyme-linked immunosorbent assay (ELISA). The expression of the microRNA, miR-129-3p, in osteoblasts was analyzed by real-time quantitative polymerase chain reaction (qPCR). Immunoreactive proteins were spotted by Western blotting. We used the collagen-induced arthritis (CIA) mouse model to investigate the role of OPN in monocyte migration during RA. OPN and IL-17 expression were higher in RA synovial fluid as compared to OA samples. We also found that OPN promotes IL-17 expression in osteoblasts and thereby enhances monocyte migration via t...
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The choice of primary hip hemiarthroplasty or total hip arthroplasty for displaced femoral neck fracture is still controversial. Revision hip arthroplasty not only increases risk and cost but also could result in worse outcome.... more
The choice of primary hip hemiarthroplasty or total hip arthroplasty for displaced femoral neck fracture is still controversial. Revision hip arthroplasty not only increases risk and cost but also could result in worse outcome. Determining the risk factors for revision can help inform medical decision-making and aid in risk stratification of publicly reported outcomes. Therefore, we conducted a nationwide population-based study to identify the disease-related risk factors and construct a risk score nomogram to predict revision surgery. Records of all 68,030 femoral neck fracture patients receiving partial hemiarthroplasty (HA) in 2000-2010, with no total hip arthroplasty (THA) or revision HA history, were collected from the National Health Insurance Research Database. Cox proportional hazard regression was used to estimate the risk of revision hip replacement (RHA). The score of each risk factor was the quotient of the regression coefficient of the variable by the regression coeffic...
Research Interests: Medicine, Population, Humans, Female, Male, and 15 moreArthroplasty, Clinical Sciences, Aged, Middle Aged, Adult, Proportional hazards model, Retrospective Studies, Orthopaedic Surgery, Risk Factors, Confidence Interval, Nomogram, Cohort Studies, Reoperation, Population surveillance, and hazard ratio
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Visfatin is an adipocytokine involving in cellular metabolism, inflammation, and cancer. This study investigated the roles of extracellular visfatin in breast cancer, and explored underlying mechanisms in clinical and experimental... more
Visfatin is an adipocytokine involving in cellular metabolism, inflammation, and cancer. This study investigated the roles of extracellular visfatin in breast cancer, and explored underlying mechanisms in clinical and experimental settings. Associations of serum visfatin with clinicopathological characteristics and patient survival were assessed with Cox regression models and Kaplan-Meier analyses. Effects of extracellular visfatin on cultured breast cancer cells were examined, followed by in vivo investigation of tumor growth and metastasis in xenograft animal models. Imatinib and Stattic were utilized to inhibit c-Abl and STAT3 activation, respectively. Breast cancer patients with high serum visfatin levels were associated with advanced tumor stage, increased tumor size and lymph node metastasis, and poor survival. Elevated phosphorylation of c-Abl and STAT3 in breast tumor tissues were correlated with high serum visfatin levels in patients. Visfatin-promoted in vitro cell viabili...
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The β-nitrostyrene family has been shown to suppress cancer cell proliferation and induce programmed cell death. However, mechanisms underlying β-nitrostyrenes remain less evaluated. Here, we synthesized a β-nitrostyrene derivative,... more
The β-nitrostyrene family has been shown to suppress cancer cell proliferation and induce programmed cell death. However, mechanisms underlying β-nitrostyrenes remain less evaluated. Here, we synthesized a β-nitrostyrene derivative, CYT-Rx20, and characterized its anticancer effect and involving mechanisms in breast cancer. We found that CYT-Rx20 arrested breast cancer cells at G2/M phase and decreased cell viability by activating the caspase cascade, accompanying with increases of poly (ADP-ribose) polymerase (PARP) cleavage and γ-H2AX expression. On the other hand, up-regulation of Beclin-1, ATG5, and LC-3 was observed in CYT-Rx20-induced autophagy, which was evidently shown by transmission electron microscopy. In addition to these, CYT-Rx20-induced breast cancer cell death, intracellular reactive oxygen species (ROS) formation and expression of phospho-ERK1/2, Beclin-1, and LC-3 were significantly reversed in the presence of N-acetyl-l-cysteine (NAC), a thiol antioxidant. Further...
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Exposure to arsenic is known to be a risk factor for various types of cancer. In this study, we report that Id1 mediates arsenic-induced angiogenesis through PI3K/Akt, NF-κB, and nitric oxide synthase (NOS) signaling.
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The name of the first author is incorrect. The correct name is: Chun-Hao Tsai. The correct citation is: Tsai C-H, Muo C-H, Tzeng H-E, Tang C-H, Hsu H-C, et al. (2013) Fracture in Asian Women with Breast Cancer Occurs at Younger Age. PLoS... more
The name of the first author is incorrect. The correct name is: Chun-Hao Tsai. The correct citation is: Tsai C-H, Muo C-H, Tzeng H-E, Tang C-H, Hsu H-C, et al. (2013) Fracture in Asian Women with Breast Cancer Occurs at Younger Age. PLoS ONE 8(9): e75109. doi:10.1371/journal.pone.0075109.
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Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. CCN3, also called nephroblastoma overexpressed gene... more
Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. CCN3, also called nephroblastoma overexpressed gene (NOV), regulates proliferation and differentiation of cancer cells. However, the effect of CCN3 on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that CCN3 increased the migration and expression of matrix metalloproteinase (MMP)-13 in human chondrosarcoma cells (JJ012 cells). αvβ3 or αvβ5 monoclonal antibody (mAb), phosphatidylinositol 3-kinase (PI3K) inhibitors (Ly294002 and wortmannin) and Akt inhibitor inhibited the CCN3-induced increase of the migration and MMP-13 upregulation of chondrosarcoma cells. CCN3 stimulation increased the phosphorylation of focal adhesion kinase (FAK), PI3K, and Akt. In addition, NF-κB inhibitors also suppressed the cell migration and MMP-13 expression enhanced by CCN3. Moreover, CCN3 increased NF-κB luciferase activity and binding of p65 to the NF-κB element on the MMP-13 promoter. Taken together, our results indicate that CCN3 enhances the migration of chondrosarcoma cells by increasing MMP-13 expression through the αvβ3/αvβ5 integrin receptor, FAK, PI3K, Akt, p65, and NF-κB signal transduction pathway.
Research Interests: Biology, Cell Migration, Cancer Research, Medicine, Signal Transduction, and 15 moreRNA interference, Humans, Mutation, Phosphorylation, Cellular Physiology, Medical Physiology, Protein kinase B, Neoplasm Invasiveness, Time Factors, Protein Kinase Inhibitors, Ly, Focal Adhesion Kinase, Matrix Metalloproteinase, binding sites, and Chondrosarcoma
Chemokine (C-C motif) ligand 3 (CCL3), also known as macrophage inflammatory protein-1α, is a cytokine involved in inflammation and activation of polymorphonuclear leukocytes. CCL3 has been detected in infiltrating cells and tumor cells.... more
Chemokine (C-C motif) ligand 3 (CCL3), also known as macrophage inflammatory protein-1α, is a cytokine involved in inflammation and activation of polymorphonuclear leukocytes. CCL3 has been detected in infiltrating cells and tumor cells. Chondrosarcoma is a highly malignant tumor that causes distant metastasis. However, the effect of CCL3 on human chondrosarcoma metastasis is still unknown. Here, we found that CCL3 increased cellular migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. Pre-treatment of cells with the MMP-2 inhibitor or transfection with MMP-2 specific siRNA abolished CCL3-induced cell migration. CCL3 has been reported to exert its effects through activation of its specific receptor, CC chemokine receptor 5 (CCR5). The CCR5 and AMP-activated protein kinase (AMPK) inhibitor or siRNA also attenuated CCL3-upregulated cell motility and MMP-2 expression. CCL3-induced expression of MMP-2 and migration were also inhibited by specific i...
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Research Interests: Chemistry, Stem Cells, Cancer Research, Medicine, Multidisciplinary, and 15 moreMAP Kinase pathway and its regulation, Angiogenesis, Signal Transduction, RNA interference, Cell Differentiation, Humans, Endothelial Cells, Osteosarcoma, Monoclonal Antibodies, Cytokine, BIOCHEMICAL PHARMACOLOGY, Vascular Endothelial Growth Factor, Interleukin, real time polymerase chain reaction, and Pharmacology and pharmaceutical sciences(MAP Kinase pathway and its regulation, Angiogenesis, Signal Transduction, RNA interference, Cell Differentiation, Humans, Endothelial Cells, Osteosarcoma, Monoclonal Antibodies, Cytokine, BIOCHEMICAL PHARMACOLOGY, Vascular Endothelial Growth Factor, Interleukin, real time polymerase chain reaction, and Pharmacology and pharmaceutical sciences)
(MAP Kinase pathway and its regulation, Angiogenesis, Signal Transduction, RNA interference, Cell Differentiation, Humans, Endothelial Cells, Osteosarcoma, Monoclonal Antibodies, Cytokine, BIOCHEMICAL PHARMACOLOGY, Vascular Endothelial Growth Factor, Interleukin, real time polymerase chain reaction, and Pharmacology and pharmaceutical sciences)
Osteoarthritis (OA) is a chronic inflammatory and progressive joint disease that results in cartilage degradation and subchondral bone remodeling. The proinflammatory cytokine interleukin 1 beta (IL-1β) is abundantly expressed in OA and... more
Osteoarthritis (OA) is a chronic inflammatory and progressive joint disease that results in cartilage degradation and subchondral bone remodeling. The proinflammatory cytokine interleukin 1 beta (IL-1β) is abundantly expressed in OA and plays a crucial role in cartilage remodeling, although its role in the activity of chondrocytes in cartilage and subchondral remodeling remains unclear. In this study, stimulating chondrogenic ATDC5 cells with IL-1β increased the levels of bone morphogenetic protein 2 (BMP-2), promoted articular cartilage degradation, and enhanced structural remodeling. Immunohistochemistry staining and microcomputed tomography imaging of the subchondral trabecular bone region in the experimental OA rat model revealed that the OA disease promotes levels of IL-1β, BMP-2, and matrix metalloproteinase 13 (MMP-13) expression in the articular cartilage and enhances subchondral bone remodeling. The intra-articular injection of Noggin protein (a BMP-2 inhibitor) attenuated ...
Research Interests: Chemistry, Medicine, Osteoarthritis, Cartilage, Cells, and 3 moreChondrogenesis, Bone remodeling, and Noggin
Chondrosarcoma, a common malignant tumor, develops in bone. Effective adjuvant therapy remains inadequate for treatment, meaning poor prognosis. It is imperative to explore novel remedies. Angiogenesis is a rate-limiting step in... more
Chondrosarcoma, a common malignant tumor, develops in bone. Effective adjuvant therapy remains inadequate for treatment, meaning poor prognosis. It is imperative to explore novel remedies. Angiogenesis is a rate-limiting step in progression that explains neovessel formation for blood supply in tumor microenvironment. Numerous studies indicate endothelial progenitor cells (EPCs) promoting angiogenesis and contributing to tumor growth. Basic fibroblast growth factor (bFGF), a secreted cytokine, regulates biological activity including angiogenesis and correlates with tumorigenesis. However, the role of bFGF in angiogenesis-related tumor progression by recruiting EPCs in human chondrosarcoma is rarely discussed. Here, we found bFGF induced vascular endothelial growth factor (VEGF) expression via FGFR1/c-Src/p38/NF-κB signaling pathway in chondrosarcoma cells, thereby triggering angiogenesis of endothelial progenitor cells. Our in vivo data revealed tumor-secreted bFGF promoting angiogen...
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Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis. Angiogenesis is a critical step in tumor growth and metastasis. Chemokine CCL5 (previously called RANTES) has been... more
Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis. Angiogenesis is a critical step in tumor growth and metastasis. Chemokine CCL5 (previously called RANTES) has been shown to facilitate tumor progression and metastasis. However, the relationship of CCL5 with vascular endothelial growth factor (VEGF) expression and angiogenesis in human chondrosarcoma is mostly unknown. In this study, CCL5 increased VEGF expression and also promoted chondrosarcoma medium-mediated angiogenesis in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and Matrigel plug nude mice model in vivo. MicroRNA analysis was performed in CCL5-treated chondrosarcoma cells versus control cells to investigate the mechanism of CCL5-mediated promotion of chondrosarcoma angiogenesis. Among the miRNAs regulated by CCL5, miR-199a was the most downregulated miRNA after CCL5 treatment. In addition, co-transfection with miR-199a mim...
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Endothelial progenitor cells (EPCs) promote angiogenesis and are therefore key contributors to a wide variety of angiogenesis-related autoimmune diseases such as rheumatoid arthritis (RA). However, the signaling mechanisms through which... more
Endothelial progenitor cells (EPCs) promote angiogenesis and are therefore key contributors to a wide variety of angiogenesis-related autoimmune diseases such as rheumatoid arthritis (RA). However, the signaling mechanisms through which these progenitor cells influence RA pathogenesis remain unknown. The aim of this study was to examine whether resistin plays a role in the pathogenesis of and angiogenesis associated with RA by circulating EPCs. We found that levels of resistin in synovial fluid and tissue from patients with RA and from mice with collagen-induced arthritis were overexpressed and promoted the homing of EPCs into the synovium, thereby inducing angiogenesis. EPCs isolated from healthy donors were used to investigate the signal transduction pathway underlying EPC migration and tube formation after treatment with resistin. We found that resistin directly induced a significant increase in expression of vascular endothelial growth factor (VEGF) in EPCs. We also found that t...
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Inflammatory response and articular destruction are common symptoms of osteoarthritis. Cysteine-rich 61 (CCN1 or Cyr61), a secreted protein from the CCN family, is associated with the extracellular matrix involved in many cellular... more
Inflammatory response and articular destruction are common symptoms of osteoarthritis. Cysteine-rich 61 (CCN1 or Cyr61), a secreted protein from the CCN family, is associated with the extracellular matrix involved in many cellular activities like growth and differentiation. Yet the mechanism of CCN1 interacting with arthritic inflammatory response is unclear. This study finds CCN1 increasing expression of oncostatin m (OSM) in human osteoblastic cells. Pretreatment of αvβ3 monoclonal antibody and inhibitors of focal adhesion kinase (FAK), c-Src, phosphatidylinositol 3-kinase (PI3K), and NF-κB inhibited CCN1-induced OSM expression in osteoblastic cells. Stimulation of cells with CCN1 increased phosphorylation of FAK, c-Src, PI3K, and NF-κB via αvβ3 receptor; CCN1 treatment of osteoblasts increased NF-κB-luciferase activity and p65 binding to NF-κB element on OSM promoter. Results indicate CCN1 heightening OSM expression via αvβ3 receptor, FAK, c-Src, PI3K, and NF-κB signal pathway in...
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Resistin is a recently discovered adipocyte-secreting adipokine, which may play a critical role in modulating cancer pathogenesis. Chondrosarcoma is a highly malignant tumor known to frequently metastasize; however, the role of resistin... more
Resistin is a recently discovered adipocyte-secreting adipokine, which may play a critical role in modulating cancer pathogenesis. Chondrosarcoma is a highly malignant tumor known to frequently metastasize; however, the role of resistin in the metastasis of human chondrosarcoma is largely unknown. Here, we found that the expression of resistin was higher in chondrosarcoma biopsy tissues than in normal cartilage. Moreover, treatment with resistin increased matrix metalloproteinase (MMP)-2 expression and promoted cell migration in human chondrosarcoma cells. Co-transfection with microRNA (miR)-519d mimic resulted in reversed resistin-mediated cell migration and MMP-2 expression. Additionally, AMP-activated protein kinase (AMPK) and p38 inhibitors or siRNAs reduced the resistin-increased cell migration and miR-519d suppression, and inhibition of resistin expression resulted in suppression of MMP-2 expression and lung metastasis in vivo. Taken together, our results indicate that resisti...
Research Interests:
Research Interests:
A case report and review of the literature. To report a rare case of bacteremia coexisting with spinal gout initially suspected as pyogenic spondylodiscitis. Gouty spine is a rare disease. It is even rare when coexisting with bacteremia.... more
A case report and review of the literature. To report a rare case of bacteremia coexisting with spinal gout initially suspected as pyogenic spondylodiscitis. Gouty spine is a rare disease. It is even rare when coexisting with bacteremia. The presentation as pain, fever, and positive blood culture will make it more difficult to distinguish from spinal infection. A 64-year-old woman with type II diabetes mellitus and chronic renal insufficiency was admitted to the emergency department with a fever of 39 degrees C, chills, and back pain. Laboratory studies revealed an elevated white count and neutrophils; her serum glucose level was 279 mg/dL. The C-reactive protein level was 25.55 mg/dL and serum uric acid was in the upper range of normal. Blood cultures revealed Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis. Urine culture revealed 3 separate gram-negative bacilli. Magnetic resonance imaging of the spine revealed contrast enhancement in the L4-L5 and T5-T9 vertebr...
Research Interests:
Research Interests:
Bone morphogenic protein (BMP)-7 is a member of the transforming growth factor (TGF)-beta superfamily, which is originally identified based on its ability to induce cartilage and bone formation. In recent years, BMP-7 is also defined as a... more
Bone morphogenic protein (BMP)-7 is a member of the transforming growth factor (TGF)-beta superfamily, which is originally identified based on its ability to induce cartilage and bone formation. In recent years, BMP-7 is also defined as a potent promoter of cell motility, invasion, and metastasis. However, there is little knowledge of the role of BMP-7 and its cellular function in chondrosarcoma cells. In the present study, we investigated the biological impact of BMP-7 on cell motility using transwell assay. In addition, the intracellular signaling pathways were also investigated by pharmacological and genetic approaches. Our results demonstrated that treatment with exogenous BMP-7 markedly increased cell migration by activating c-Src/PI3K/Akt/IKK/NF-κB signaling pathway, resulting in the transactivation of αvβ3 integrin expression. Indeed, abrogation of signaling activation, by chemical inhibition or expression of a kinase dead form of the protein attenuated BMP-7-induced expressi...