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Role of bone marrow adipogenesis for bone formation and its abnormality in senile osteoporosis

Research Project

Project/Area Number 13671150
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionThe University of Tokyo

Principal Investigator

TAKEUCHI Yasuhiro  The University of Tokyo, Faculty of Medicine, research associate, 医学部附属病院, 助手 (50202164)

Co-Investigator(Kenkyū-buntansha) NAKAYAMA Konosuke  The University of Tokyo, Faculty of Medicine, research associate, 医学部附属病院, 助手 (20322076)
FUKUMOTO Seiji  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (30202287)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsosteoblast / adipocyte / interleukin-11 / PPARγ / bone marrwo stromal cell / transgenio mine / osteoporosis / bone formation / Smad
Research Abstract

1) Role of interteukin-11(IL-11) in adipogenesis and osteoblastogenesis in bone marrow.
We have previously shown that decreased IL-11 expression is tightly associated with impaired bone formation in senile osteoporosis model SAM-P6 mice. To further investigate how IL-11 is involved in bone metabolism, we examined effects of IL-11 on differentiation of both adipocytes and osteoblasts in bone marrow. Our results indicate that IL-11 inhibits transcriptional activity of PPARγ, essential for adipocyte differentiation, and stimulates that of Smad1, indispensable for osteoblastic differentiation
2) In vivo effects of IL-11 on bone metabolism
We next investigated effects of IL-11 on bone metabolism in vivo using tansgenic mice overexpressing human IL-11 gene. Bone formation was stimulated but bone resorption was not changed in IL-11 transgenic mice, resulting in thicker and stronger cortical bone than control littermates. More importantly, cortical bone loss was not observed in IL-11 transgenic mice with aging. These results suggest that IL-11 stimulates bone formation and prevents bone loss with aging.
3) Involvement of PPARγ in osteoblastogenesis and adipngenflsis in bone marrow
We examined if PPARγ was involved in osteoblastogenesis as well as adipogenesis in bone marrow stromal cells, using mouse bone marrow stromal cell line ST2 stably expressing dominant negative PPARγ (DN-ST2). DN-ST2 cells were confirmed not to be differentiated into adipocytes. These cells were also not differentiated into osteoblasts in vitro, suggesing that PPARγ actions are required for osteobliastogenesis.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (49 results)

All Other

All Publications (49 results)

  • [Publications] Shimada T, et al.: "Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia"Proc Natl Acad Sci USA. 98(11). 6500-6505 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukumoto S, et al.: "Inactivating mutations of calcium-sensing receptor results in parathyroid lipohyperplasia"Diag Mol Pathol. 10(4). 242-247 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe S, et al.: "Effects of 1-year treatment with fluvastatin or parvastatin on bone"Am J Med. 110(7). 584-587 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamura Y, et al.: "Focal adhesion kinase activity is required for bone morphogenetic protein-Smadl signaling and osteoblastic differentiation in murine MC3T3-El cells"J Bone Miner Res. 16(10). 1772-1779 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzawa M, et al.: "Stimulation of Smadl transcriptional activity by Ras-extracellular signal-regulated kinase pathway : a possible mechanism for collagen-dependent osteoblasticdifferentiation"J Bone Miner Res. 17(2). 240-248 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chikatsu N, et al.: "Clonal endothelial cells produce humoral factors that inhibit osteoclast-like cell formation in vitro"Endocr J. 49(4). 439-447 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeuchi Y, et al.: "Parathyroid hormone-related protein induced coupled increases in bone formation and resorption markers for 7 years in a patient with malignant islet cell tumors"J Bone Miner Res. 17(5). 753-757 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe S, et al.: "Association between activating mutations of calcium-sensing receptor and Bartter's syndrome"Lancet. 360. 692-694 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimada T, et al.: "Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes"Endocrinology. 143(8). 3179-3182 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamazaki Y, et al.: "Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic"J Clin Endocrinol Metab. 87(11). 4957-4960 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeuchi Y, et al.: "Interleukin-11 as a stimulatory factor for bone formation prevents bone loss with advancing age in mice"J Biol Chem. 277(50). 49011-49018 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chikatsu N, et al.: "A family of autosomal dominant hypocalcemia with an activating mutation of calcium-sensing receptor gene"Endocr J. 50(1). 91-96 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzawa M, et al.: "Cytokines suppress adipogenesis and PPAR-γ function through the TAK1/TAB1/NIK cascade"Nat Cell Biol. (In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe S, et al.: "Decrease in serum leptin by troglitazone is associated with preventing bone loss in type 2 diabetic patients"J Bone Miner Metab. (In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakayama K, et al.: "Receptor tyrosine kinases inhibit bone morphogenetic protein-Smad responsive promoter activity and differentiation of murine MC3T3-E1 osteoblast-like cells"J Bone Miner Res. (In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshijima E, et al.: "Decreased AP-1 activity and interleukin-11 expression by bone marrow stromal cells may be associated with impaired bone formation in aged mice"J Bone Miner Res. (In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S, Takeuchi Y, Fujita T, Fiilcnmntn S, and Yamashita T.: "Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia"Proc Nail Acad Sci USA. 98(11). 6500-6505 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukumoto S. Chikatsu N, Okazaki R, Takeuchi Y, Tamura Y, Murakami T, Obara T, and Fujita T.: "Inactivating mutations of calcium-sensing receptor results in parathyroid lipohyperplasia"Diag Mol Pathol. 10(4). 242-247 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe S. Fukumoto S, Takeuchi Y, Fujita H, Nakano T, and Fujita T.: "Effects of 1-year treatment with fluvastatin or pravastatin on bone"Am J Med. 110(7). 584-587 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamura Y, Takeuchi Y, Suzawa M, Fukumoto S, Kato M, Miyazono K, and Fujita T.: "Focal adhesion kinase activity is required for bone morphogenetic protein-Smad1 signaling and osteoblastic differentiation in murine MC3T3-E1 cells"J Bone Miner Res. 16(10). 1772-1779 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzawa M, Tamura Y, Fukumoto S, Miyazono K, Fujita T, Kato S, and Takeuchi Y.: "Stimulation of Smad1 transcriptional activity by Ras-extracellular signal-regulated kinase pathway : a possible mechanism for collagen-dependent osteoblastic differentiation"J Bone Miner Res. 17(2). 240-248 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chikatsu N, Takeuchi Y, Fukumoto S, Yano K, Fujita N, Tsuruo T, and Fujita T.: "Clonal endothellal cells produce humoral factors that inhibit osteoclast-like cell formation in vitro"Endocr J. 49(4). 439-447 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeuchi Y, Fukumoto S, Nakayama K, Tamura Y, Yanagisawa A, and Fujita T.: "Parathyroid hormone-related protein induced coupled increases in bone formation and resorption markers for 7 years in a patient with malignant islet cell tumors"J Bone Miner Res. 17(5). 753-757 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe S, Fukumoto S, Chang H, Takeuchi Y, Hasegawa Y, Okazaki R, Chikatsu N, and Fujita T.: "Association between activating mutations of calcium-sensing receptor and Banter's syndrome"Lancet. 360. 692-694 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimada T, Muto T, Urakawa I, Yoneya T, Yamazaki Y, Okawa K, Takeuchi Y, Fujita T, Fukumoto S; and Yamashita T: "Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in vivo"Endocrinology. 143(8). 3179-3182 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamazaki Y, Okazaki R, Shibata M, Hasegawa Y, Satoh K, Tajima T, Takeuchi Y, Fujita T, Nakahara K, Yamashita T, and Fukumoto S.: "Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia"J Clin Endocrinol Metab. 87(11). 4957-4960 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeuchi Y- Watanabe S, Ishii G, Takeda S, Nakayama K. Fukumoto S, Kaneta Y, Inoue D, Matsumoto T, Harigaya K, and Fujita T.: "Interleukin-11 as a stimulatory factor for bone formation prevents bone loss with advancing age in mice"J Biol Chem. 277(50). 49011-49018 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chikatsu N, Watanabe S, Takeuchi Y. Muraosa Y, Sasaki S, Oka Y, Fuknmoto S. and Fujita T.: "A family of autosomal dominant hypocalcemia with an activating mutation of calcium-sensing receptor gene"Endocr J. 50(1). 91-96 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzawa M, Takada I, Yanagisawa J, Ohtake F, Ogawa S, Yamauchi T, Kadowaki T, Takeuchi Y, Shibuya H, Gotoh Y, Matsumoto K, and Kato S.: "Cytokines suppress adipogenesis and PPAR-y function through the TAK1/TABI/NIK cascade"Nat Cell Biol. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe S, Takeuchi Y, Fukumoto S, Fujita H, Nakano T, and Fujita T.: "Decrease in serum leptin by troglitazone is associated with preventing bone loss in type 2 diabetic patients"J Bone Miner Metab. 21. 166-171 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakayama K, Tamura Y, Suzawa M, Harada S, Fukumoto S, Kato M, Miyazono K, Rodan GA, Takeuchi Y, and Fujita T.: "Receptor tyrosine kinases inhibit bone morphogenetic protein-Smad responsive promoter activity and differentiation of murine MC3T3-E1 osteoblast-like cells"J Bone Miner Res. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tohjima E, Inoue D, Yamamoto N, Kido S, Ito Y, Kato S, Takeuchi Y, Fukumoto S, and Matsumoto T.: "Decreased AP-1 activity and interleukin-11 expression by bone marrow stromal cells may be associated with impaired bone formation in aged mice"J Bone Miner Res. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chikatsu N, et al.: "Clonal endothelial cells produce factors that inhibit osteoclast-like cell formation in vitro"Endocr J. 49(4). 439-447 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takeuchi Y, et al.: "Parathyroid hormone-related protein induced coupled increases in bone formation and resorption markers for 7 years in a patient with malignant islet cell tumors"J Bone Miner Res. 17(5). 753-757 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Watanabe S, et al.: "Association between activating mutations of calcium-sensing receptor and Bartter's syndrome"Lancet. 360. 692-694 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimada T, et al.: "Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes"Endocrinology. 143(8). 3179-3182 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamazaki Y. et al.: "Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic"J Clin Endocrinol Metab. 87(11). 4957-4960 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takeuchi Y, et al.: "Interleukin-11 as a stimulatory factor for bone formation prevents bone loss with advancing age in mice"J Biol Chem. 277(50). 49011-49018 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Chikatsu N, et al.: "A family of autosomal dominant hypocalcemia with an activating mutation of calcium-sensing receptor gene"Endocr J. 50(1). 91-96 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzawa M, et al.: "Cytokines suppress adipogenesis and PPAR-γ function through the TAK1/TAB1/NIK cascade"Nat Cell Biol. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Watanabe S, et al.: "Decrease in serum leptin by troglitazone id associated with preventing bone loss in type 2 diabetic patients"J Bone Miner Metab. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakayama K, et al.: "Receptor tyrosine kinases inhibit bone morphogenetic protein-Smad responsive promoter activity and differentiation of murine MC3T3-E1 osteoblast-like cells"J Bone Miner Res. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Toshijima E, et al.: "Decreased AP-1 activity and interleukin-11 expression by bone marrow stromal cells may be associated with impaired bone formation in aged mice"J Bone Miner Res. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Watanabe S. et al.: "Effects of one year treatment with statins on bone"Am J Med. 110(5). 584-587 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimada T. et al.: "Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia"Proc Natl Acad Sci USA. 98(11). 6500-6505 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tamura Y. et al.: "Focal adhesion kinase activity is required for bone morphogenetic protein-Smadl signaling and osteoblastic differentiation in murine MC3T3-E1 cells"J Bone Miner Res. 16(10). 1772-1779 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukumoto S. et al.: "Inactivating mutations of calcium-sensing receptor results in parathyroid lipohyperplasia"Diagnostic Molecular Pathology. 10(4). 242-247 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suzawa M. et al.: "Stimulation of Smadl Transcriptional activity by Ras-extracellular signal-regulated kinase pathway : a possible mechanism for collagen-dependent osteoblastic differentiation"J Bone Miner Res. 17(2). 240-248 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takeuchi Y. et al.: "Parathyroid hormone-related protein induced coupled increase in bone formation and resorption markers for seven years in a patient with malignant islet cell tumors"J Bone Miner Res. (in press). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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