No abstract available.
Shoulder Fractures*

Osteocytes may function as mechanotransducers by regulating local osteoclastogenesis. Reduced availability of oxygen, i.e. hypoxia, could occur during disuse, bone development, and fracture. Receptor activator of nuclear factor-kappaB ligand (RANKL) is an osteoblast/stromal cell derived essential factor for osteoclastogenesis. The hypoxia induced osteoclastogenesis via increased RANKL expression in osteoblasts was demonstrated. Hypoxic regulation of gene expression generally involves activation of the hypoxia-inducible factor (HIF) transcription pathway. In the present study, we investigated whether hypoxia regulates RANKL expression in murine osteocytes and HIF-1alpha mediates hypoxia-induced RANKL expression by transactivating RANKL promoter, to elucidate the role of osteocyte in osteoclastogenesis in the context of hypoxic condition. The expression levels of RANKL mRNA and protein, as well as hypoxia inducible factor-1alpha (HIF-1alpha) protein, were significantly increased in hypoxic condition in MLO-Y4s. Constitutively active HIF-1alpha alone significantly increased the levels of RANKL expression in MLO-Y4s under normoxic conditions, whereas dominant negative HIF-1alpha blocked hypoxia-induced RANKL expression. To further explore to find if HIF-1alpha directly regulates RANKL transcription, a luciferase reporter assay was conducted. Hypoxia significantly increased RANKL promoter activity, whereas mutations of putative HIF-1alpha binding elements in RANKL promoter prevented this hypoxia-induced RANKL promoter activity in MLO-Y4s. These results suggest that HIF-1alpha mediates hypoxia-induced up-regulation of RANKL expression, and that in osteocytes of mechanically unloaded bone, hypoxia enhances osteoclastogenesis, at least in part, via an increased RANKL expression in osteocytes.
Anoxia* ; Bone Development ; Gene Expression Regulation ; Luciferases ; Osteoblasts ; Osteocytes* ; Oxygen ; RANK Ligand* ; RNA, Messenger ; Up-Regulation

Receptor activator of nuclear factor-κB ligand (RANKL) is an osteoblast/stromal cell-derived essential factor for osteoclastogenesis. During endochondral bone formation, hypertrophic chondrocytes calcify cartilage matrix that is subsequently resorbed by osteoclasts in order to be replaced by new bone. Hypoxia-induced upregulation of RANKL expression has been previously demonstrated in an in vitro system using osteoblasts; however, the involved mechanism remains unclear in chondrocytes. In the present study, we investigated whether hypoxia regulates RANKL expression in ATDC5 cells, a murine chondrogenic cell line, and hypoxia-inducible factor-1α (HIF-1α) mediates hypoxia-induced RANKL expression by transactivating the RANKL promoter. The expression levels of RANKL mRNA and protein, as well as HIF-1α protein, were significantly increased in ATDC5 cells under hypoxic condition. Constitutively active HIF-1α alone significantly increased the levels of RANKL expression under normoxic conditions, whereas dominant negative HIF-1α reduced hypoxia-induced RANKL expression. HIF-1α increased RANKL promoter reporter activity in a HIF-1α binding element-dependent manner in ATDC5 cells. Hypoxia-induced RANKL levels were much higher in differentiated ATDC5 cells, as compared to proliferating ATDC5 cells. These results suggested that under hypoxic conditions, HIF-1α mediates induction of RANKL expression in chondrocytes; in addition, hypoxia plays a role in osteoclastogenesis during endochondral bone formation, at least in part, through the induction of RANKL expression in hypertrophic chondrocytes.
Anoxia* ; Cartilage ; Cell Line ; Chondrocytes* ; Osteoblasts ; Osteoclasts ; Osteogenesis ; RANK Ligand ; RNA, Messenger ; Up-Regulation

Tumor necrosis factor alpha (TNFalpha) is a multifunctional inflammatory cytokine that regulates various cellular and biological processes. Increased levels of TNFalpha have been implicated in a number of human diseases including diabetes and arthritis. Sympathetic nervous system stimulation via the beta2-adrenergic receptor (beta2AR) in osteoblasts suppresses osteogenic activity. We previously reported that TNFalpha up-regulates beta2AR expression in murine osteoblastic cells and that this modulation is associated with TNFalpha inhibition of osteoblast differentiation. In our present study, we explored whether TNFalpha induces beta2AR expression in human osteoblasts and then identified the downstream signaling pathway. Our results indicated that beta2AR expression was increased in Saos-2 and C2C12 cells by TNFalpha treatment, and that this increase was blocked by the inhibition of NF-kappaB activation. Chromatin immunoprecipitation and luciferase reporter assay results indicated that NF-kappaB directly binds to its cognate elements on the beta2AR promoter and thereby stimulates beta2AR expression. These findings suggest that the activation of TNFalpha signaling in osteoblastic cells leads to an upregulation of beta2AR and also that TNFalpha induces beta2AR expression in an NF-kappaB-dependent manner.
Arthritis ; Biological Processes ; Chromatin Immunoprecipitation ; Durapatite ; Humans ; Luciferases ; NF-kappa B ; Osteoblasts ; Receptors, Adrenergic ; Sympathetic Nervous System ; Tumor Necrosis Factor-alpha ; Up-Regulation

We report the case of a recurrent carotid cavernous fistula (CCF) originating from a giant cerebral aneurysm (GCA) after placement of a covered stent. A 47-year-old woman presented with sudden onset of severe headache, and left-sided exophthalmos and ptosis. Cerebral angiography revealed a CCF caused by rupture of a GCA in the cavernous segment of the left internal carotid artery. Two covered stents were placed at the neck of the aneurysm. The neurological symptoms improved at first, but were aggravated in the 6 months following the treatment. Contrast agent endoleak was seen in the distal area of the stent. Even though additional treatments were attempted via an endovascular approach, the CCF could not be cured. However, after trapping the aneurysm using coils and performing superficial temporal artery-middle cerebral artery bypass, the neurological symptoms improved. In cases of recurrent CCF originating from a GCA after placement of a covered stent, it is possible to treat the CCF by endovascular trapping and surgical bypass.
Aneurysm ; Carotid Artery, Internal ; Carotid-Cavernous Sinus Fistula ; Cerebral Angiography ; Cerebral Arteries ; Endoleak ; Exophthalmos ; Female ; Fistula* ; Headache ; Humans ; Intracranial Aneurysm* ; Middle Aged ; Neck ; Rupture ; Stents*

OBJECTIVE: Selecting an appropriate guiding catheter to provide both sufficient supportability for working devices and sufficient distal navigability is essential for ensuring the success of a procedure. This study aimed to evaluate the advantages and disadvantages of using the ENVOY 6F distal access (DA) guiding catheter in coil embolization of anterior circulation cerebral aneurysms.METHODS: We included 98 patients (72 [73.5%] women, median age: 63 [range: 25–84] years) who underwent endovascular coiling with the ENVOY 6F DA guiding catheter from May to November 2016. We analyzed data on patient demographics and the number of co-axial techniques to position the guiding catheter, initial and final location of the catheter, and complications related to the catheter.RESULTS: The co-axial technique was used to position the ENVOY 6F DA guiding catheter in the internal carotid artery (ICA) in 20 cases (20.41%). The initial position of the ENVOY 6F DA guiding catheter involved the cervical ICA (79.6%), horizontal petrous ICA (17.3%), and vertical petrous ICA (3.1%). Final control angiograms after endovascular coiling showed proximal change in the final, compared to the initial, position of the ENVOY 6F DA guiding catheter in 25 cases (25.51%). Procedure-related complications were observed in nine patients (9.18%), involving vasospasm in all cases; however, there was no symptomatic case.CONCLUSION: The ENVOY 6F DA guiding catheter had relatively sufficient distal navigability without symptomatic procedural complications. However, the change in the catheter position after endovascular coiling denoted insufficient supportability.
Aneurysm ; Carotid Arteries ; Carotid Artery, Internal ; Catheterization ; Catheters ; Cerebrovascular Circulation ; Demography ; Embolization, Therapeutic ; Female ; Humans ; Intracranial Aneurysm

High ambient Ca2+ at bone resorption sites have been implicated to play an important role in the regulation of bone remodeling. The present study was performed to clarify the mode of high extracellular Ca2+ (Ca2+e)-induced modulation of osteoclastogenesis and the expression of receptor activator of nuclear factor-kB ligand (RANKL) and osteoprotegerin (OPG), thereby to define its role in osteoclast formation. Mouse bone marrow cells were cocultured with osteoblastic cells in the absence or presence of osteoclastogenic factors such as 1,25-dihydroxyvitaminD3 (1,25-(OH)2vitD3) and macrophage colony-stimulating factor/soluble RANKL. Ca2+ concentration in media (1.8 mM) was adjusted to 3, 5, 7 or 10 mM. Osteoclast formation was confirmed by the appearance of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells and the expression of osteoclast phenotypic markers (calcitonin receptor, vitronectin receptor, cathepsin K, matrix metalloproteinase-9, carbonic anhydrase 2). High Ca2+e alone significantly stimulated osteoclast formation in a dose-dependent manner. However, in the presence of highly osteoclastogenic factors, high Ca2+e significantly inhibited osteoclastogenesis. High Ca2+e alone continuously up-regulated RANKL expression while only transiently increased OPG expression. However, in the presence of 1,25-(OH)2vitD3, high Ca2+e did not change the 1,25-(OH)2vitD3- induced RANKL expression while increased OPG expression. Taken together, these findings suggest that high Ca2+e alone increase osteoclastogenesis but inhibit in the presence of other osteoclastogenic factors. In addition, high Ca2+e-induced osteoclastogenesis may be mediated by osteoblasts via up-regulation of RANKL expression. Meanwhile up-regulated OPG might participate in the inhibitory effect of high Ca2+e on 1,25-(OH)2vitD3-induced osteoclastogenesis.
Animals ; Bone Marrow Cells/metabolism/physiology ; Bone Remodeling ; Calcium/*metabolism ; Carrier Proteins/biosynthesis ; Cations, Divalent ; Cells, Cultured ; Coculture ; Extracellular Space/*metabolism ; Glycoproteins/biosynthesis ; Membrane Glycoproteins/biosynthesis ; Mice ; Mice, Inbred ICR ; Osteoblasts/*cytology/metabolism ; Osteoclasts/*cytology/metabolism ; Receptors, Cytoplasmic and Nuclear/biosynthesis ; Vitamin D/*analogs & derivatives/pharmacology

Multiple primary cancer is defined as the case of primary malignant tumors of different histologic origins each other in one person, The incidence of multiple primary cancer has been increasing recently due to more developed diagnostie procedure and long survival of cancer patients. In esophageal cancer patients, comibined prevalence of other malignancy is rela tively high. We have experienced three cases of gastric adenocarcinoma with esophageal squamous cell carcinoma and report these cases with a review of literatures.
Adenocarcinoma ; Carcinoma, Squamous Cell ; Esophageal Neoplasms ; Esophagus* ; Humans ; Incidence ; Prevalence ; Stomach*

Receptor activator of NF-kappaB ligand (RANKL) is an essential cytokine for osteoclast differentiation, activation and survival. T lymphocytes such as T17 cells, a subset of T helper cells that produce IL-17, play an important role in rheumatoid arthritic bone resorption by producing inflammatory cytokines and RANKL. It has not yet been clearly elucidated how T cell activation induces RANKL expression. T cell receptor activation induces the activation of nuclear factor of activated T cell (NFAT) and expression of its target genes. In this study, we examined the role of NFAT in T cell activation-induced RANKL expression. EL-4, a murine T lymphocytic cell line, was used. When T cell activation was induced by phorbol 12-myristate 13-acetate (PMA) and ionomycin, RANKL expression increased in a time-dependent manner. In the presence of cyclosporin, an inhibitor of NFAT activation, this PMA/ionomycin-induced RANKL expression was blocked. Overexpression of either NFATc1 or NFATc3 induced RANKL expression. Chromatin immunoprecipitation results demonstrated that PMA/ionomycin treatment induced the binding of NFATc1 and NFATc3 to the mouse RANKL gene promoter. These results suggest that NFATc1 and NFATc3 mediates T cell receptor activation-induced RANKL expression in T lymphocytes.
Animals ; Bone Resorption ; Cell Line ; Chromatin Immunoprecipitation ; Cyclosporine ; Cytokines ; Interleukin-17 ; Ionomycin ; Mice ; NFATC Transcription Factors ; Osteoclasts ; Phorbols ; RANK Ligand ; Receptor Activator of Nuclear Factor-kappa B ; Receptors, Antigen, T-Cell ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer

Glucosamine is commonly taken by the elderly without prescription as a nutritional supplement to attenuate the progression or symptoms of osteoarthritis. Previous studies demonstrated that glucosamine shows anti-inflammatory effects in tissues such as blood vessels and the heart. However, there have been few reports about the effects of glucosamine on oral inflammatory diseases. Therefore, in this study, the effects of glucosamine on lipopolysaccharide (LPS)-induced inflammatory responses were investigated using human periodontal ligament fibroblasts (HPDLFs). HPDLFs were incubated in the presence and absence of glucosamine (10 mM) for 24 h, followed by treatment with E. coli LPS (100 ng/ml) or vehicle. Quantitative RT-PCR and ELISA results showed that LPS exposure significantly increased the levels of IL-6 and IL-8 mRNA and protein, while the effect was significantly suppressed by glucosamine treatment. Glucosamine did not attenuate, but slightly increased, the LPS-induced activation of mitogen activated kinases (ERK, p38, JNK). However, it suppressed the LPS-induced increase in the DNA binding affinity and transcriptional activity of NF-kappaB. These results suggest that glucosamine exerts anti-inflammatory effects on HPDLFs exposed to LPS via inhibition of NF-kappaB activity, necessitating further studies using animal periodontitis models.
Aged ; Animals ; Blood Vessels ; DNA ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts* ; Glucosamine* ; Heart ; Humans ; Inflammation ; Interleukin-6 ; Interleukin-8 ; NF-kappa B ; Osteoarthritis ; Periodontal Ligament* ; Periodontitis ; Phosphotransferases ; Prescriptions ; RNA, Messenger