Age-related changes in expression of tissue inhibitor of metalloproteinases-3 associated with transition from the notochordal nucleus pulposus to the fibrocartilaginous nucleus pulposus in rabbit intervertebral disc

Takashi Tsuji, Kazuhiro Chiba, Hideaki Imabayashi, Yoshinari Fujita, Naobumi Hosogane, Yasunori Okada, Yoshiaki Toyama

Research output: Contribution to journalArticle

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Abstract

STUDY DESIGN. Experimental study on age-related changes in expression of tissue inhibitor of metalloproteinases-3 (TIMP-3) associated with transition from notochordal nucleus pulposus (NP) to fibrocartilaginous NP in rabbit intervertebral disc (IVD). OBJECTIVES. To identify roles of notochordal NP in extracellular matrix (ECM) metabolism of IVD. SUMMARY OF BACKGROUND DATA. One of most interesting properties of TIMP-3 is to inhibit aggrecanases in addition to matrix metalloproteinases. Balance of aggrecanase/TIMP-3 is critical to maintain homeostasis of ECM metabolism. METHODS. Four-week-old and 160-week-old male Japanese white rabbits were used. Age-related changes in IVDs were evaluated histologically using previously established grading system. Immunohistochemistry of TIMP-3 and semiquantitative reverse transcriptase- polymerase reaction (RT-PCR) of TIMP-3, a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTS) 4, 5, and transforming growth factor-β1 (TGF-β1), were conducted. RESULTS. Semiquantitative assessment of histologic changes indicated that 4-week-old rabbit was equivalent to fetus to 2-year-old human and 160-week-old rabbit was equivalent to 11- to 30-year-old human, particularly 11- to 16-year-old, which corresponds to transition period from notochordal to fibrocartilaginous NP. Immunohistochemistry revealed that TIMP-3 was positive in 4-week-old rabbit only. Semiquantitative RT-PCR revealed that levels of expressions of TGF-β1 and TIMP-3 mRNAs in 4-week-old were significantly higher than those in 160-week-old rabbits. There was no significant difference in expression of ADAMTS4 mRNA. ADAMTS5 mRNA was not detected or extremely low in both groups. Expression of TIMP-3 mRNA in NP was upregulated by TGF-β1 but was not affected by IL-1β. On the contrary, expression of ADAMTS4 mRNA was not upregulated by TGF-β1 but was upregulated by IL-1β. CONCLUSIONS. Levels of expression of TIMP-3 in notochordal NP were significantly lower in 160-week-old rabbits than those in 4-week-old rabbits. Decrease in expression of TIMP-3, possibly mediated in part by TGF-β1, may cause imbalance of ADAMTS4/TIMP-3 ratio at transition period from notochordal to fibrocartilaginous NP.

Original languageEnglish
Pages (from-to)849-856
Number of pages8
JournalSpine
Volume32
Issue number8
DOIs
Publication statusPublished - 2007 Apr

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Tissue Inhibitor of Metalloproteinase-3
Intervertebral Disc
Rabbits
Transforming Growth Factors
Messenger RNA
Interleukin-1
Extracellular Matrix
Nucleus Pulposus
Immunohistochemistry
Disintegrins
Polymerase Chain Reaction
RNA-Directed DNA Polymerase
Metalloproteases
Matrix Metalloproteinases
Fetus

Keywords

  • A disintegrin and metalloproteinases with thrombospondin motifs 4
  • Intervertebral disc
  • Notochordal nucleus pulposus
  • Tissue inhibitor of metalloproteinases-3
  • Transforming growth factor-β1

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Orthopedics and Sports Medicine

Cite this

Age-related changes in expression of tissue inhibitor of metalloproteinases-3 associated with transition from the notochordal nucleus pulposus to the fibrocartilaginous nucleus pulposus in rabbit intervertebral disc. / Tsuji, Takashi; Chiba, Kazuhiro; Imabayashi, Hideaki; Fujita, Yoshinari; Hosogane, Naobumi; Okada, Yasunori; Toyama, Yoshiaki.

In: Spine, Vol. 32, No. 8, 04.2007, p. 849-856.

Research output: Contribution to journalArticle

Tsuji, Takashi ; Chiba, Kazuhiro ; Imabayashi, Hideaki ; Fujita, Yoshinari ; Hosogane, Naobumi ; Okada, Yasunori ; Toyama, Yoshiaki. / Age-related changes in expression of tissue inhibitor of metalloproteinases-3 associated with transition from the notochordal nucleus pulposus to the fibrocartilaginous nucleus pulposus in rabbit intervertebral disc. In: Spine. 2007 ; Vol. 32, No. 8. pp. 849-856.
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title = "Age-related changes in expression of tissue inhibitor of metalloproteinases-3 associated with transition from the notochordal nucleus pulposus to the fibrocartilaginous nucleus pulposus in rabbit intervertebral disc",
abstract = "STUDY DESIGN. Experimental study on age-related changes in expression of tissue inhibitor of metalloproteinases-3 (TIMP-3) associated with transition from notochordal nucleus pulposus (NP) to fibrocartilaginous NP in rabbit intervertebral disc (IVD). OBJECTIVES. To identify roles of notochordal NP in extracellular matrix (ECM) metabolism of IVD. SUMMARY OF BACKGROUND DATA. One of most interesting properties of TIMP-3 is to inhibit aggrecanases in addition to matrix metalloproteinases. Balance of aggrecanase/TIMP-3 is critical to maintain homeostasis of ECM metabolism. METHODS. Four-week-old and 160-week-old male Japanese white rabbits were used. Age-related changes in IVDs were evaluated histologically using previously established grading system. Immunohistochemistry of TIMP-3 and semiquantitative reverse transcriptase- polymerase reaction (RT-PCR) of TIMP-3, a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTS) 4, 5, and transforming growth factor-β1 (TGF-β1), were conducted. RESULTS. Semiquantitative assessment of histologic changes indicated that 4-week-old rabbit was equivalent to fetus to 2-year-old human and 160-week-old rabbit was equivalent to 11- to 30-year-old human, particularly 11- to 16-year-old, which corresponds to transition period from notochordal to fibrocartilaginous NP. Immunohistochemistry revealed that TIMP-3 was positive in 4-week-old rabbit only. Semiquantitative RT-PCR revealed that levels of expressions of TGF-β1 and TIMP-3 mRNAs in 4-week-old were significantly higher than those in 160-week-old rabbits. There was no significant difference in expression of ADAMTS4 mRNA. ADAMTS5 mRNA was not detected or extremely low in both groups. Expression of TIMP-3 mRNA in NP was upregulated by TGF-β1 but was not affected by IL-1β. On the contrary, expression of ADAMTS4 mRNA was not upregulated by TGF-β1 but was upregulated by IL-1β. CONCLUSIONS. Levels of expression of TIMP-3 in notochordal NP were significantly lower in 160-week-old rabbits than those in 4-week-old rabbits. Decrease in expression of TIMP-3, possibly mediated in part by TGF-β1, may cause imbalance of ADAMTS4/TIMP-3 ratio at transition period from notochordal to fibrocartilaginous NP.",
keywords = "A disintegrin and metalloproteinases with thrombospondin motifs 4, Intervertebral disc, Notochordal nucleus pulposus, Tissue inhibitor of metalloproteinases-3, Transforming growth factor-β1",
author = "Takashi Tsuji and Kazuhiro Chiba and Hideaki Imabayashi and Yoshinari Fujita and Naobumi Hosogane and Yasunori Okada and Yoshiaki Toyama",
year = "2007",
month = "4",
doi = "10.1097/01.brs.0000259804.39881.62",
language = "English",
volume = "32",
pages = "849--856",
journal = "Spine",
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TY - JOUR

T1 - Age-related changes in expression of tissue inhibitor of metalloproteinases-3 associated with transition from the notochordal nucleus pulposus to the fibrocartilaginous nucleus pulposus in rabbit intervertebral disc

AU - Tsuji, Takashi

AU - Chiba, Kazuhiro

AU - Imabayashi, Hideaki

AU - Fujita, Yoshinari

AU - Hosogane, Naobumi

AU - Okada, Yasunori

AU - Toyama, Yoshiaki

PY - 2007/4

Y1 - 2007/4

N2 - STUDY DESIGN. Experimental study on age-related changes in expression of tissue inhibitor of metalloproteinases-3 (TIMP-3) associated with transition from notochordal nucleus pulposus (NP) to fibrocartilaginous NP in rabbit intervertebral disc (IVD). OBJECTIVES. To identify roles of notochordal NP in extracellular matrix (ECM) metabolism of IVD. SUMMARY OF BACKGROUND DATA. One of most interesting properties of TIMP-3 is to inhibit aggrecanases in addition to matrix metalloproteinases. Balance of aggrecanase/TIMP-3 is critical to maintain homeostasis of ECM metabolism. METHODS. Four-week-old and 160-week-old male Japanese white rabbits were used. Age-related changes in IVDs were evaluated histologically using previously established grading system. Immunohistochemistry of TIMP-3 and semiquantitative reverse transcriptase- polymerase reaction (RT-PCR) of TIMP-3, a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTS) 4, 5, and transforming growth factor-β1 (TGF-β1), were conducted. RESULTS. Semiquantitative assessment of histologic changes indicated that 4-week-old rabbit was equivalent to fetus to 2-year-old human and 160-week-old rabbit was equivalent to 11- to 30-year-old human, particularly 11- to 16-year-old, which corresponds to transition period from notochordal to fibrocartilaginous NP. Immunohistochemistry revealed that TIMP-3 was positive in 4-week-old rabbit only. Semiquantitative RT-PCR revealed that levels of expressions of TGF-β1 and TIMP-3 mRNAs in 4-week-old were significantly higher than those in 160-week-old rabbits. There was no significant difference in expression of ADAMTS4 mRNA. ADAMTS5 mRNA was not detected or extremely low in both groups. Expression of TIMP-3 mRNA in NP was upregulated by TGF-β1 but was not affected by IL-1β. On the contrary, expression of ADAMTS4 mRNA was not upregulated by TGF-β1 but was upregulated by IL-1β. CONCLUSIONS. Levels of expression of TIMP-3 in notochordal NP were significantly lower in 160-week-old rabbits than those in 4-week-old rabbits. Decrease in expression of TIMP-3, possibly mediated in part by TGF-β1, may cause imbalance of ADAMTS4/TIMP-3 ratio at transition period from notochordal to fibrocartilaginous NP.

AB - STUDY DESIGN. Experimental study on age-related changes in expression of tissue inhibitor of metalloproteinases-3 (TIMP-3) associated with transition from notochordal nucleus pulposus (NP) to fibrocartilaginous NP in rabbit intervertebral disc (IVD). OBJECTIVES. To identify roles of notochordal NP in extracellular matrix (ECM) metabolism of IVD. SUMMARY OF BACKGROUND DATA. One of most interesting properties of TIMP-3 is to inhibit aggrecanases in addition to matrix metalloproteinases. Balance of aggrecanase/TIMP-3 is critical to maintain homeostasis of ECM metabolism. METHODS. Four-week-old and 160-week-old male Japanese white rabbits were used. Age-related changes in IVDs were evaluated histologically using previously established grading system. Immunohistochemistry of TIMP-3 and semiquantitative reverse transcriptase- polymerase reaction (RT-PCR) of TIMP-3, a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTS) 4, 5, and transforming growth factor-β1 (TGF-β1), were conducted. RESULTS. Semiquantitative assessment of histologic changes indicated that 4-week-old rabbit was equivalent to fetus to 2-year-old human and 160-week-old rabbit was equivalent to 11- to 30-year-old human, particularly 11- to 16-year-old, which corresponds to transition period from notochordal to fibrocartilaginous NP. Immunohistochemistry revealed that TIMP-3 was positive in 4-week-old rabbit only. Semiquantitative RT-PCR revealed that levels of expressions of TGF-β1 and TIMP-3 mRNAs in 4-week-old were significantly higher than those in 160-week-old rabbits. There was no significant difference in expression of ADAMTS4 mRNA. ADAMTS5 mRNA was not detected or extremely low in both groups. Expression of TIMP-3 mRNA in NP was upregulated by TGF-β1 but was not affected by IL-1β. On the contrary, expression of ADAMTS4 mRNA was not upregulated by TGF-β1 but was upregulated by IL-1β. CONCLUSIONS. Levels of expression of TIMP-3 in notochordal NP were significantly lower in 160-week-old rabbits than those in 4-week-old rabbits. Decrease in expression of TIMP-3, possibly mediated in part by TGF-β1, may cause imbalance of ADAMTS4/TIMP-3 ratio at transition period from notochordal to fibrocartilaginous NP.

KW - A disintegrin and metalloproteinases with thrombospondin motifs 4

KW - Intervertebral disc

KW - Notochordal nucleus pulposus

KW - Tissue inhibitor of metalloproteinases-3

KW - Transforming growth factor-β1

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