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  1. Article ; Online: Equivalent osteoblastic differentiation function of human mesenchymal stem cells from rheumatoid arthritis in comparison with osteoarthritis.

    Morimoto, Daiki / Kuroda, Shoko / Kizawa, Takuji / Nomura, Koji / Higuchi, Chikahisa / Yoshikawa, Hideki / Tomita, Tetsuya

    Rheumatology (Oxford, England)

    2009  Volume 48, Issue 6, Page(s) 643–649

    Abstract: Objective: To evaluate the osteoblastic differentiation of human mesenchymal stem cells (hMSCs) in patients with RA.: Methods: Heparinized bone marrow aspirate was obtained from patients with OA and RA. Mononuclear cells were cultured for 2 weeks and ...

    Abstract Objective: To evaluate the osteoblastic differentiation of human mesenchymal stem cells (hMSCs) in patients with RA.
    Methods: Heparinized bone marrow aspirate was obtained from patients with OA and RA. Mononuclear cells were cultured for 2 weeks and a colony-forming assay was performed. The phenotype of cells was analysed by flow cytometry. Passage 2 cells were cultured with beta-glycerophosphate (bGP) in the control group and bGP, ascorbic acid and dexamethasone in the differentiation group. After 2 weeks, ALP staining and activity were performed. After 3 weeks, Alizarin Red S assay was performed. Total RNA was extracted from cells cultured for 2 and 3 weeks. Gene expression of bone formation factor was examined by real-time PCR.
    Results: The phenotype of cells was identical in both OA and RA and the content was thought to be hMSCs. The results of ALP activity and Alizarin Red S assay showed higher levels in the differentiation group for both OA and RA samples compared with the control group. The results of a colony-forming assay were identical in both OA and RA samples. Gene expression in the differentiation group was higher than in the control group in both OA and RA samples. There was no significant difference between OA and RA samples in all experiments.
    Conclusion: The function of osteoblastic differentiation of hMSCs is similar between OA and RA.
    MeSH term(s) Aged ; Aged, 80 and over ; Alkaline Phosphatase/analysis ; Arthritis, Rheumatoid/pathology ; Biomarkers/analysis ; Case-Control Studies ; Cell Culture Techniques ; Cell Differentiation ; Cells, Cultured ; Colony-Forming Units Assay ; Female ; Flow Cytometry ; Gene Expression ; Humans ; Mesenchymal Stromal Cells/pathology ; Middle Aged ; Osteoarthritis/pathology ; Osteoblasts/pathology ; Osteocalcin/analysis ; Osteopontin/analysis ; Phenotype ; Reverse Transcriptase Polymerase Chain Reaction/methods ; Staining and Labeling ; Statistics, Nonparametric
    Chemical Substances Biomarkers ; Osteocalcin (104982-03-8) ; Osteopontin (106441-73-0) ; Alkaline Phosphatase (EC 3.1.3.1)
    Language English
    Publishing date 2009-06
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/kep044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Angiotensin II accelerates osteoporosis by activating osteoclasts

    Shimizu, Hideo / Nakagami, Hironori / Osako, Mariana Kiomy / Hanayama, Rie / Kunugiza, Yasuo / Kizawa, Takuji / Tomita, Tetsuya / Yoshikawa, Hideki / Ogihara, Toshio / Morishita, Ryuichi

    FASEB journal. 2008 July, v. 22, no. 7

    2008  

    Abstract: Recent clinical studies suggest that several antihypertensive drugs, especially angiotensin-converting enzyme inhibitors, reduced bone fractures. To clarify the relationship between hypertension and osteoporosis, we focused on the role of angiotensin II ( ...

    Abstract Recent clinical studies suggest that several antihypertensive drugs, especially angiotensin-converting enzyme inhibitors, reduced bone fractures. To clarify the relationship between hypertension and osteoporosis, we focused on the role of angiotensin II (Ang II) on bone metabolism. In bone marrow-derived mononuclear cells, Ang II (1x10⁻⁶ M) significantly increased tartrate-resistant acid phosphatase (TRAP) -positive multinuclear osteoclasts. Of importance, Ang II significantly induced the expression of receptor activator of NF-κB ligand (RANKL) in osteoblasts, leading to the activation of osteoclasts, whereas these effects were completely blocked by an Ang II type 1 receptor blockade (olmesartan) and mitogen-activated protein kinase kinase inhibitors. In a rat ovariectomy model of estrogen deficiency, administration of Ang II (200 ng/kg/min) accelerated the increase in TRAP activity, accompanied by a significant decrease in bone density and an increase in urinary deoxypyridinoline. In hypertensive rats, treatment with olmesartan attenuated the ovariectomy-induced decrease in bone density and increase in TRAP activity and urinary deoxypyridinoline. Furthermore, in wild-type mice ovariectomy with five-sixths nephrectomy decreased bone volume by microcomputed tomography, whereas these change was not detect in Ang II type 1a receptor-deficient mice. Overall, Ang II accelerates osteoporosis by activating osteoclasts via RANKL induction. Blockade of Ang II might become a novel therapeutic approach to prevent osteoporosis in hypertensive patients.--Shimizu, H., Nakagami, H., Osako, M. K., Hanayama, R., Kunugiza, Y., Kizawa, T., Tomita, T., Yoshikawa, H., Ogihara, T., Morishita, R. Angiotensin II accelerates osteoporosis by activating osteoclasts.
    Language English
    Dates of publication 2008-07
    Size p. 2465-2475.
    Publishing place The Federation of American Societies for Experimental Biology
    Document type Article
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages.

    Kawane, Kohki / Ohtani, Mayumi / Miwa, Keiko / Kizawa, Takuji / Kanbara, Yoshiyuki / Yoshioka, Yoshichika / Yoshikawa, Hideki / Nagata, Shigekazu

    Nature

    2006  Volume 443, Issue 7114, Page(s) 998–1002

    Abstract: A large amount of chromosomal DNA is degraded during programmed cell death and definitive erythropoiesis. DNase II is an enzyme that digests the chromosomal DNA of apoptotic cells and nuclei expelled from erythroid precursor cells after macrophages have ... ...

    Abstract A large amount of chromosomal DNA is degraded during programmed cell death and definitive erythropoiesis. DNase II is an enzyme that digests the chromosomal DNA of apoptotic cells and nuclei expelled from erythroid precursor cells after macrophages have engulfed them. Here we show that DNase II-/-IFN-IR-/- mice and mice with an induced deletion of the DNase II gene develop a chronic polyarthritis resembling human rheumatoid arthritis. A set of cytokine genes was strongly activated in the affected joints of these mice, and their serum contained high levels of anti-cyclic citrullinated peptide antibody, rheumatoid factor and matrix metalloproteinase-3. Early in the pathogenesis, expression of the gene encoding tumour necrosis factor (TNF)-alpha was upregulated in the bone marrow, and administration of anti-TNF-alpha antibody prevented the development of arthritis. These results indicate that if macrophages cannot degrade mammalian DNA from erythroid precursors and apoptotic cells, they produce TNF-alpha, which activates synovial cells to produce various cytokines, leading to the development of chronic polyarthritis.
    MeSH term(s) Animals ; Arthritis/genetics ; Arthritis/metabolism ; Autoimmune Diseases/genetics ; Autoimmune Diseases/metabolism ; Chronic Disease ; DNA/blood ; DNA/metabolism ; Endodeoxyribonucleases/deficiency ; Endodeoxyribonucleases/genetics ; Endodeoxyribonucleases/metabolism ; Female ; Macrophages/metabolism ; Male ; Mice ; Receptors, Interferon/deficiency ; Receptors, Interferon/genetics ; Receptors, Interferon/metabolism
    Chemical Substances Receptors, Interferon ; DNA (9007-49-2) ; Endodeoxyribonucleases (EC 3.1.-) ; deoxyribonuclease II (EC 3.1.22.1)
    Language English
    Publishing date 2006-10-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/nature05245
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Angiotensin II accelerates osteoporosis by activating osteoclasts.

    Shimizu, Hideo / Nakagami, Hironori / Osako, Mariana Kiomy / Hanayama, Rie / Kunugiza, Yasuo / Kizawa, Takuji / Tomita, Tetsuya / Yoshikawa, Hideki / Ogihara, Toshio / Morishita, Ryuichi

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2008  Volume 22, Issue 7, Page(s) 2465–2475

    Abstract: Recent clinical studies suggest that several antihypertensive drugs, especially angiotensin-converting enzyme inhibitors, reduced bone fractures. To clarify the relationship between hypertension and osteoporosis, we focused on the role of angiotensin II ( ...

    Abstract Recent clinical studies suggest that several antihypertensive drugs, especially angiotensin-converting enzyme inhibitors, reduced bone fractures. To clarify the relationship between hypertension and osteoporosis, we focused on the role of angiotensin II (Ang II) on bone metabolism. In bone marrow-derived mononuclear cells, Ang II (1x10(-6) M) significantly increased tartrate-resistant acid phosphatase (TRAP) -positive multinuclear osteoclasts. Of importance, Ang II significantly induced the expression of receptor activator of NF-kappaB ligand (RANKL) in osteoblasts, leading to the activation of osteoclasts, whereas these effects were completely blocked by an Ang II type 1 receptor blockade (olmesartan) and mitogen-activated protein kinase kinase inhibitors. In a rat ovariectomy model of estrogen deficiency, administration of Ang II (200 ng/kg/min) accelerated the increase in TRAP activity, accompanied by a significant decrease in bone density and an increase in urinary deoxypyridinoline. In hypertensive rats, treatment with olmesartan attenuated the ovariectomy-induced decrease in bone density and increase in TRAP activity and urinary deoxypyridinoline. Furthermore, in wild-type mice ovariectomy with five-sixths nephrectomy decreased bone volume by microcomputed tomography, whereas these change was not detect in Ang II type 1a receptor-deficient mice. Overall, Ang II accelerates osteoporosis by activating osteoclasts via RANKL induction. Blockade of Ang II might become a novel therapeutic approach to prevent osteoporosis in hypertensive patients.
    MeSH term(s) Acid Phosphatase/metabolism ; Angiotensin II/toxicity ; Animals ; Bone Marrow Cells/drug effects ; Bone Marrow Cells/physiology ; Cell Differentiation/drug effects ; Cell Differentiation/physiology ; Humans ; Osteoclasts/cytology ; Osteoclasts/physiology ; Osteoporosis/chemically induced ; Osteoprotegerin/genetics ; RANK Ligand/genetics ; Rabbits ; Reverse Transcriptase Polymerase Chain Reaction
    Chemical Substances Osteoprotegerin ; RANK Ligand ; Angiotensin II (11128-99-7) ; Acid Phosphatase (EC 3.1.3.2)
    Language English
    Publishing date 2008-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.07-098954
    Database MEDical Literature Analysis and Retrieval System OnLINE

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