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Role of local factors on growth and aging of mandibular condylar cartilage

Research Project

Project/Area Number 63440072
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionOsaka University

Principal Investigator

SUZUKI Fujio  Faculty of Dentistry Osaka University Professor, 歯学部, 教授 (40028717)

Co-Investigator(Kenkyū-buntansha) ASADA Akira  Faculty of Dentistry Osaka University Assistant Professor, 歯学部, 講師 (50028734)
KATO Yukio  Faculty of Dentistry Hiroshima University Professor, 歯学部, 教授 (10112062)
Project Period (FY) 1988 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥29,700,000 (Direct Cost: ¥29,700,000)
Fiscal Year 1991: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥9,500,000 (Direct Cost: ¥9,500,000)
Fiscal Year 1988: ¥16,000,000 (Direct Cost: ¥16,000,000)
KeywordsMandibular Condylar artilage / Organ Culture / Growth Factor / TGF-beta / FGF / Chondromodulin / Articular Cartilage / コンドロモジュリン / 軟骨 / 関節 / 成長 / 老化 / 下顎頭 / アルカリホスファターゼ
Research Abstract

Autocrineand local factors may play key roles in the development and growth of skeletal tissues in fetal stage. We examined the effects of TGF-beta on organ cultures of mandibular condylar cartilage, isolated from fetal mice. When they were cultured with TGF-beta, new chondroblasts developed which subsequently matured showing signs of hypertrophy and formation of cartilage-specific proteoglycans. DNA synthesis increased rapidly, reaching a maximum 2 days after addition of TGF-beta. Autoradiography showed that highly labeled cells were confined to the precartilage progenitor zone. The label was then transferred to matured chondrocytes after 2 days. In contrast, TGF-beta decreased alkaline phosphatase activity and ^<45>Ca uptake. Similar results were obtained following the addition of bFGF. These findings indicated that local factors are functioning as regulators of chondroprogenitor cell growth and expression of the differentiated cartilage phenotype.
We succeeded in purification from fetal bovine cartilage of a cartilage-specific growth modulating factor that functions in growth regulation of the differentiated chondrocytes. We named this principle "Chondromodulin-I (ChMI). Mature ChM-I consists of 122 amino acids with 3 glycosylation sites and is coded as the C-terminal part of a larger precursor. The precursor has 335 amino acids. Mature ChM-I stimulates both DNA synthesis and proteoglycan synthesis of cultured growth-plate chondrocytes. In the presence of bFGF, ChM-I synergistically stimulates the growth of cultured chondrocytes. These findings indicate that functional components of the matrix participate in physiological regulation of cellular growth and differentiation. In addition to endocrine, paracrine, and autocrine routes, cellular interaction with matrix-adsorbed factors such as ChM-I could be called "auto-matrierine".

Report

(5 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • 1988 Annual Research Report
  • Research Products

    (59 results)

All Other

All Publications (59 results)

  • [Publications] Y.Kato,M.Iwamoto,T.Koike,F.Suzuki & Y.Takano: "Terminal differentiation and calcification in rabbit chondrocyte cultures in centrifuge tubes:Regulation by transforming growth factor-beta and serum factors" Proc.Natl.Acad.Sci.USA. 85. 9552-9556 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Kato,A.Shimazu,M.Iwamoto,K.Nakashima,T.Koike,F.Suzuki,Y.Nishii & K.Sato: "Role of 1,25-dihydroxycholecalciferol in growth-plate cartilage:Inhibition of terminal differentiation of chodnrocytes in vivo and in vitro" Proc.natl.Acad.sci.USA. 87. 6522-6526 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Hiraki,H.Inoue,A.Asada & F.Suzuki: "Differential modulation of growth and phenotypic expression of chondrocytes in sparse and confluent cultures by growth factors in cartilage" J.Bone Mineral Res.5. 1077-1085 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M.Iwamoto,A.Shimazu,K.Nakashima,F.Suzuki & Y.Kato: "Reduction in basic fibroblast growth factor receptor is coupled with terminal differentiation of chondrocytes" J.Biol.Chem.266. 461-467 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Hiraki,H.Inoue,C.Shigeno,Y.Samma,H.Bentz,D.A.Rosen,A.Asada & F.Suzuki: "Bone morphogenetic proteins (BMP-2 and BMP-3) promotes growth and expression of the differentiated phenotype of rabbit chondrocytes and osteoblastic MC3T3-E1 cells in vitro" J.Bone Mineral Res.6. 1373-1385 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Hiraki,H.Tanaka,H.Inoue,J.Kondo,A.Kamizono & F.Suzuki: "Molecular cloning of a new class of cartilage-specific matrix,chondromodulin-I,which stimulates growth of cultured chondrocytes" Biochem.Biophys.Res.Commun.175. 971-977 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] F.Suzuki,Y.Hiraki & F.Suzuki: "Method in Enzymology,146(Pepetide Growth Factor),Part A,pp.313-320(D.Barnes & D.A.Sirbasku,eds.) Preparation of cartilage-derived factor" Academic Press,Orlando,Florida,USA, 452 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Kato,K.Nakashima,K.Sato,W.Q.Yan,M.Iwamoto & F.Suzuki: "Methods in Enzymology,198(Peptide Growth Factors),pp.416-424(D.A.Sirbasku,J.P.Mather & G.Sato,eds.)Purification of growth factors from cartilage" Academic Press,Orlando,Florida,USA, 578 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] F. Suzuki, Y. Hiraki & Y. Kato: "Preparation of cartilage-derived factor" Methods in Enzymology. 146 (Peptide growth factor), Part A. 313-320 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Hiraki, H. Inoue, R. Hirai, Y. Kato & F. Suzuki: "Effect of transforming growth factor-beta on cell proliferation and glycosaminoglycan synthesis by rabbit growth-plate chondrocytes in culture" Biochim. Biophys.969. 91-99 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Kato, M. Iwamoto, T. Koike & F. Suzuki: "Terminal differentiation and calcification in rabbit chondrocyte cultures in centrifuge tubes : Regulation by transforming growth factor-beta and serum factors." Proc. Natl.85. 9552-9556 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Inoue, K. Hiasa, Y. Samma, O. Nakamura, M. Sakuda, M. Iwamoto, F. Suzuki & Y. Kato: "Stimulation of proteoglycan and DNA syntheses in chondrocytes by centrifugation." J. Dent. Res.69. 1560-1563 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Koike, M. Iwamoto, A. Shimazu, K. Nakashima, F. Suzuki & Y. Kato: "Potent mitogenic effects of parathyroid hormone (PTH) on embryonic chick and rabbit chondrocytes. Differential effects of age on growth, proteoglycan, and cyclic AMP responses of chondrocytes to PTH." J. Clin, Invest.85. 626-631 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] K. Sato, M. Iwamoto, A. shimazu, K. Nakashima, F. Suzuki & Y. Kato: "1-alpha, 25-Dihydroxyvitanin D_3 stimulates colony formation of chick embryo chondrocytes in soft agar." Exp. Cell Res.187. 335-338 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Kato, A. Shimazu, M. Iwamoto, K. Nakashima, T. Koike, F. Suzuki, Y. Nishii & K. Sato: "Role of 1, 25-dihydroxycholecalciferol in growth-plate cartilage : Inhibition of terminal differentiation of chondrocytes in vivo and in vitro." Proc, Natl. Acad. Sci. USA. 87. 6522-6526 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Hiraki, H. Inoue, A. Asada & F. Suzuki: "Differential modulation of growth and phenotypic expression of chondrocytes in sparse and confluent cultures by growth factors in cartilage." J. Bone Mineral Res.5. 1077-1085 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M. Iwamoto, A. Shimazu, K. Nakashima, F. Suzuki & Y. Kato: "Reduction in basic fibroblast growth factor receptor is coupled with terminal differentiation of chondrocytes" J. Biol. Chem.266. 461-467 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Inoue, J. Kato, M. Sakuda, M. Iwamoto, F. Suzuki & Y. Kato: "Effects of mechanical forces on proliferation of rabbit growth-plate and articular chondrocytes and their extracellular matrix synthesis in pelleted cultures." Fundamentals of Bone Growth : Methodology and Applications (A. d. Dixon, B. G. Sarnat & D. A. N. Hoyte, eds.). 407-415 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Kato, K. Nakashima, K. Sato, W. Q. Yan, M. Iwamoto & F. Suzuki: "Purification of growth factors from cartilage" Methods in Enzymology (D. A. Sirbasku, J. P. Mather & G. Sato, eds.). 198 (Peptide growth factors). 416-424 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Hiraki, H. Inoue, C. Shigeno, Y. Samma, H. Bentz, D. A. Rosen, A. Asada & F. Suzuki: "Bone morphogenetic proteins (BMP-2 and BMP-3) promotes growth and expression of the differentiated phenotype of rabbit chondrocytes and osteoblastic MC3T3-El cell in vitro." J. Bone Mineral Res. 6. 1373-1385 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Hiraki, H. Tanaka, H. Inoue, J. Kondo, A. Kamizono & F. Suzuki: "Molecular cloning of a new class of cartilage-specific matrix, chondromodulin-I, which stimulates growth of cultured chondrocytes." Biochem. Biophys. Res. Commun.175. 971-977 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M.Iwamoto,,A.Shimazu,,K.Nakashima,,F.Suzuki & Y.Kato: "Reduction in basic fibroblast growth factor receptor is coupled with terminal differentiation of chondroctes" J.Biol.Chem.266. 461-467 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Hiraki,,H.Inoue,,C.Shigeno,,Y.Samma,,H.Bentz,,D.A.Rosen,,A.Asada & F.Suzuki: "Bone morphogenetic proteins(BMPー2 and BMPー3)promotes growth and expression of the differentiated phenotype of rabbit chondrocytes and osteoblastic MC3t3ーEl cells in vitro" J.Bone Mineral Res.6. 1373-1385 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Hiraki,,H.Tanaka,,H.Inoue,,J.Kondo,,A.Kamizono & T.Suzuki: "Molecular cloning of a new class of cartilageーspecific matrix,chondromodulinーI,which stimulates growth of cultured chondrocytes" Biochem.Biophys.Res.Commun.175. 971-977 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Kato,,K.Nakashima,,K.Sato,,W.Q.Yan,,M.Iwamoto & F.Suzuki: "Methods in Enzymology,198(Peptide Growth Factors),pp.416ー424 Purification of growth factors from catilage" Academic Press,Orlando,Florida,USA, 578

    • Related Report
      1991 Annual Research Report
  • [Publications] Tatsuya Koike et al.: "Potent Mitogenic Effects of Parathyroid Hormone(PTH) on Embryonic Chick and Rabbit Chondrocytes" J.Clin.Invest.85. 626-631 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Katsuhiko Sato et al: "1α,25ーDihydroxyvitamin D_3 Stimulates Colony Formation of Chick Embryo Chondrocytes in soft Agar" Exp.Cell Res.187. 335-338 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yukio Kato et al.: "Effects of Parathyroid Hormore and Calcification on Alkaline Phosphatase Activity and Matrix Calcification in Rabbit GrowthーPlate Chondrocyte Cultures" Endocrinology. 127. 114-118 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hiroyuki Inoue et al: "Stimulation of Proteoglycan and DNA Synthesis in Chondrocytes by Centrifugation" J.Dental Res.69. 1560-1563 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yukio Kato et al.: "Fibroblast growth factor is an inhibitor of chondrocyte terminal differentiation" J.Biol.Chem.265. 5903-5909 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Weiqun Yan et al.: "Stimulation by Concanavalin A of Cartilage matrix proteoglycan Synthesis in chondrocyte cultures" J.Biol.Chem.265. 10125-10131 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yukio Kato et al.: "Role of 1,25ーdihydroxycholecalciferol in growthーplate cartilage:inhibition of terminal differentiation of chondrocytes in vitro and in vivo." Proc.Natl.Acad.Sci.U.S.A.87. 6522-6526 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Masahiro Iwamoto et al: "Reduction in basic fibroblast growth factor receptor is coupled with terminal differentiation of chondrocytes." J.Biol.Chem.266. 461-467 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 中島 和久ら: "血小板に存在する軟骨細胞増殖因子iの精製(日本骨代謝学会奨励賞)" 日本骨代謝学会誌. 8. 255-261 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 島津 篤ら: "軟骨細胞培養系における副甲状腺ホルモンによるインスリン様成長因子の産生促進" 日本骨代謝学会誌. 9. 37-42 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Masahiro Iwamoto: "Regulation of colony formation of differentiated chondrocytes in soft agar by transformed growth factor-beta" Biochem.Biophys.Res.Commun.159. 1006-1011 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Masahiro Iwamoto: "Hypertrophy and calcification of rabbit permanent chondrocytes in pelleted cultures:synthesis of alkaline phosphatase and 1,25-dihydroxycholecalciferol receptor" Dev.Biol.136. 500-507 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Koike Tatsuya: "Potent mitogenic effects of parathyroid hormone(PTH)on embryonic chick and rabbit chondrocytes:differential effects of age on growth,proteoglycan,and cyclic AMP responses of chondrocytes to PTH" J.Clin.Invest.85. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Katsuhiko Sato: "1,apha,25-dihydroxyvitamin D3 stimulates colony formation of chick embryo chondrocytes in soft agar" Exp.Cell Res.(1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Yukio Kato: "Fibroblast growth factor is an inhibitor of chondrocyte terminal differentiation" J.Biol.Chem.265. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Yukio Kato: "Rabbit articular chondrocytes in soft agar are useful to test the effect of non-steroidal anti-inflammatory drugs on chondrocyte replication" Scand.J.Rheumatol.77(Suppl.). 3-6 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Yukio Kato: "Terminal differentiation and calcification in rabbit chondrocyte cultures grown in centrifuge tubes:regulation by transforming growth factor-beta and serum factors" Proc.Natl.Acad.Sci.U.S.A.85. 9552-9556 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] Yukio Kato: "Effects of limited exposure of rabbit chondrocyte cultures to parathyroid hormone and dibutyryl adenosine 3',5'-monophosphate on cartilage characteristic proteoglycan synthesis" Endocrinology. 122. 1991-1997 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] Yuji Hiraki: "Effect of transforming growth factor-beta on cell proliferation and glycosaminoglycan synthesis by rabbit growth-plate chondrocytes in culture" Biochim.Biophys.Acta. 969. 91-99 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] Hiroyuki Inoue: "Stimulation of cartilage-matrix proteoglycan synthesis by morphologically transformed chondrocytes grown in the presence of fibroblast growth factor and transforming growth factor-beta" J.Cell.Physiol.138. 329-337 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] M.Koji Owada: "Effects of vanadate on tyrosine phosphorylation and the pattern of glycosaminoglycan synthesis in rabbit chondrocytes in culture" J.Cell.Physiol.138. 484-492 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Masahiro Iwamoto: "Interleukin 1:a regulator of chondrocyte proliferation" Immunol.Lett.21. 153-156 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 小池達也: "軟骨細胞無血清軟寒天培養系におけるhigh-density lipoprotein(HDL)の影響" 中部日本整形外科災害外科学会誌. 32. 482-484 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 加藤幸夫: "成長因子とホルモンによる軟骨細胞のterminal differentiationと細胞外基質石灰化の制御" 日本骨代謝学会誌. 7. 16-20 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 加藤幸夫: "骨・軟骨由来成長因子" 日本臨床増刊“Receptor". 373-377 (1981)

    • Related Report
      1989 Annual Research Report
  • [Publications] 加藤幸夫: "成長板軟骨細胞の成熟、肥大、及び石灰化に伴う成長因子とホルモン受容体の変動" 日本骨代謝学会誌. 7. 26-31 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 加藤幸夫: "軟骨細胞の最終分化と石灰化:場による制御" 組織培養. 15. 390-394 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 加藤幸夫: "軟骨細胞の増殖と分化の制御" 実験医学. 7. 1279-1285 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Yukio kato: "Methods in Enzymol.Purification of various growth factors from cartilage" Academic Press Inc.,Publishers New York,

    • Related Report
      1989 Annual Research Report
  • [Publications] 佐藤克彦 他: 日本骨代謝学会雑誌. 6. 10-12 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Y.Hiraki;et al.: Biochim.Biophys.Acta. 969. 91-99 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 大前博昭 他: 歯科基礎医学会雑誌. 30. 646-651 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Y.Kato et;al: Proc.Natl.Acad.Sci.85. 9552-9556 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 加藤幸夫 他: 日本骨代謝学会雑誌. 7. 16-20 (1989)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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