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Regulation by adipocytokines of bone metabolism

Research Project

Project/Area Number 15590970
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionOkinaka Memorial Institute for Medical Research (2004)
The University of Tokyo (2003)

Principal Investigator

TAKEUCHI Yasuhiro  Okinaka Memorial Institute for Medical Research, Investigator, 研究員 (50202164)

Co-Investigator(Kenkyū-buntansha) FUKUMOTO Seiji  University of Tokyo, School of Medicine, Lecturer, 医学部附属病院, 講師 (30202287)
中山 耕之介  東京大学, 医学部附属病院, 助手 (20322076)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsadiponectin / bone marrow stromal c / osteoblast / adipocyte / osteocalcin / PPARγ / leptin
Research Abstract

1)Role of adiponectin in differentiation of bone marrow stromal cells
We examined effects of adiponectin on differentiation of mouse bone marrow stromal cell line ST2. Osteocalcin and PPARγ2 mRNA expressions were determined as osteoblastic and adipocytic differentiation markers, respectively. Cells were stained with Oil-Red O to demonstrate cellular accumulation of triglyceride. Treatment with adiponectin inhibited the expression of osteocalcin mRNA, wheras it had no effects on adipogenesis of ST2 cells. When we examined primary cultures of mouse bone marrow cells, we got essentially the same observations. Therefore, at least in mice, adiponectin seems to inhibit osteoblastic differentiation of bone marrow stromal cells and have no effects on their adipogenesis.
2)Analyses of bone obtained from transgenic mice
We next investigated effects of adiponectin on bone in vivo. First, we could not any difference of bone histology in adiponectin-transgenic mice until 10 week of age. Second, heterozygous adiponectin knock-out mice showed no skeletal abnormality at birth. Homozygous knock-out mice were embryonic lethal and have not been investigated in detail in bone histology.
3)Role of circulating leptin on bone in vivo
Recent report suggests that effects of leptin on central nervous system suppress bone formation in mice through its activation of sympathetic nervous system. We examined effects of changes of circulating leptin levels on bone metabolism in some kinds of transgenic mice. Transgenic mice overexpressing leptin in liver had low bone mass, whereas those overexpressing soluble leptin receptor showed high bone mass. Circulating leptin levels had negative correlation with bone mass in these experimental mice. Thus, it is suggested that circulating leptin also has inhibitory effects on bone formation in vivo.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (24 results)

All 2004 2003 Other

All Journal Article (18 results) Publications (6 results)

  • [Journal Article] Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism2004

    • Author(s)
      Shimada T, et al.
    • Journal Title

      J Clin Invest 113

      Pages: 561-568

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa2004

    • Author(s)
      Shimada T, et al.
    • Journal Title

      Biochem Biophys Res Commun 314

      Pages: 409-414

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis2004

    • Author(s)
      Shimada T, et al.
    • Journal Title

      J Bone Miner Res 19

      Pages: 429-435

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Venous sampling for fibroblast growth factor-23 confirms preoperative diagnosis of tumor-induced osteomalacia2004

    • Author(s)
      Takeuchi Y, et al.
    • Journal Title

      J Clin Endocrinol Metab 89

      Pages: 3979-3982

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism2004

    • Author(s)
      Shimada T, Kakitani M, Yamazaki Y, Hasegawa H, Takeuchi Y, Fujita T, Fukumoto S, Tomizuka K, Yamashita T
    • Journal Title

      J Clin Invest 113(4)

      Pages: 561-568

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type Iia2004

    • Author(s)
      Shimada T, Urakawa I, Yamazaki Y, Hasegawa H, Hino R, Yoneya T, Takeuchi Y, Fujita T, Fukumoto F, Yamashita T
    • Journal Title

      Biochem Biophys Res Commun 314

      Pages: 409-414

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis.2004

    • Author(s)
      Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, Fujita T, Nakahara K, Fukumoto S, Yamashita T
    • Journal Title

      J Bone Miner Res 19(3)

      Pages: 429-435

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Venous sampling for fibroblast growth factor-23 confirms preoperative diagnosis of tumor-induced osteomalacia.2004

    • Author(s)
      Takeuchi Y, Suzuki H, Ogura S, Imai R, Yamazaki Y, Yamashita T, Miyamoto Y, Okazaki H, Nakamura K, Nakahara K, Fukumoto S, Fujita T
    • Journal Title

      J Clin Endocrinol Metab 89(8)

      Pages: 3979-3982

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism2004

    • Author(s)
      Shimada T, et al.
    • Journal Title

      J Clin Invest 113(4)

      Pages: 561-568

    • Related Report
      2004 Annual Research Report
  • [Journal Article] FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type Iia2004

    • Author(s)
      Shimada T, et al.
    • Journal Title

      Biochem Biophys Res Commun 314

      Pages: 409-414

    • Related Report
      2004 Annual Research Report
  • [Journal Article] FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis.2004

    • Author(s)
      Shimada T, et al.
    • Journal Title

      J Bone Miner Res 19(3)

      Pages: 429-435

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Venous sampling for fibroblast growth factor-23 confirms preoperative diagnosis of tumor-induced osteomalacia.2004

    • Author(s)
      Takeuchi Y, et al.
    • Journal Title

      J ClinEndocrinol Metab 89(8)

      Pages: 3979-3982

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Receptor tyrosine kinases inhibit bone morphogenetic protein-Smad responsive promoter activity and differentiation of murine MC3T3-E1 osteoblast-like cells2003

    • Author(s)
      Nakayama K, et al.
    • Journal Title

      J Bone Miner Res 18

      Pages: 827-835

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Decreased AP-1 activity and interleukin-11 expression by bone marrow stromal cells may be associated with impaired bone formation in aged mice2003

    • Author(s)
      Toshijima E, et al.
    • Journal Title

      J Bone Miner Res 518

      Pages: 1461-1470

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Receptor tyrosine kinases inhibit bone morphogenetic protein-Smad responsive promoter activity and osteoblastic differentiation of murine MC3T3-E1 cells.2003

    • Author(s)
      Nakayama K, Tamura Y, Suzawa M, Harada S, Fukumoto S, Kato M, Miyazono K, Rodan GA, Takeuchi Y, Fujita T.
    • Journal Title

      J Bone Miner Res 18(5)

      Pages: 827-835

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Decreased AP-1 activity and interleukin-11 expression by bone marrow stromal cells may be associated with impaired bone formation in aged mice.2003

    • Author(s)
      Tohjima E, Inoue D, Yamamoto N, Kido S, Ito Y, Kato S, Takeuchi Y, Fukumoto S, Matsumoto T.
    • Journal Title

      J Bone Miner Res 18(8)

      Pages: 1461-1470

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Recepter tyosine kinases inhibit bone morphogenetic protein-Smad responsive promoter activity and differentiation of murine MC3T3-E1 osteoblast-like cells2003

    • Author(s)
      Nakayama K, et al.
    • Journal Title

      J Bone Miner Res 18(5)

      Pages: 827-835

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Decreased AP-1 activity and interleukin-11 expression by bone marrow stromal cells may be a associated with impaired bone formation in aged mice2003

    • Author(s)
      Toshijima E, et al.
    • Journal Title

      J Bone Miner Res 518(8)

      Pages: 1461-1470

    • Related Report
      2004 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
      2003 Annual Research Report
  • [Publications] Suzawa M, et al.: "Cytokines suppress adipogenesis and PPAR-γ function through the TAK1/TAB1/MIK cascade"Nat Cell Biol. 5(3). 224-230 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Watanabe S, ey al.: "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)

    • Related Report
      2003 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 teoblast-like cells"J Bone Miner Res. 18(5). 827-835 (2003)

    • Related Report
      2003 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 ckets/osteomalacia"J Bone Miner Res. 18(8). 1461-1470 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimada T, et al.: "Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism"J Clim Invest. 113. 561-568 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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