Novel chondrogenic and chondroprotective effects of the natural compound harmine

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Abstract

A significant number of natural compounds have been shown to regulate the behavior of the cells, in collaboration with cellular proteins. CCN2/connective tissue growth factor (CTGF) has been reported to have essential roles in cartilage development, chondrocyte proliferation and differentiation as well as regulation of the extracellular matrix metabolism. Previous studies demonstrated the capability of CCN2 to regenerate surgical defects in articular cartilage of rat knee. Also, transgenic mice over-expressing cartilage-specific CCN2 were shown to be more resistant to aging-related cartilage degradation. We hypothesized that small molecules that induce CCN2 in chondrocytes could be novel candidates to increase the resistance to aging-related cartilage degradation, or even to correct cartilage degenerative changes incurred in OA. Therefore, this study screened a compound library and identified the β-carboline alkaloid harmine as a novel inducer of CCN2 in human chondrocytic HCS-2/8 cells and osteoarthritic articular chondrocytes. Harmine increased the expression of the cartilage markers aggrecan and COL2α1, as well as that of the master regulator of chondrogenesis, SOX-9. Moreover, harmine notably induced chondrogenesis of prechondrocytic ATDC5 cells in micromass cultures. The chondroprotective effect of harmine was investigated under inflammatory condition by stimulation with TNFα, and harmine was shown to ameliorate TNFα-induced decrease in expression of CCN2 and cartilage markers. These findings uncover novel chondrogenic effects of harmine and indicate harmine as a potential drug for prevention and/or repair of cartilage degradation.

Original languageEnglish
Pages (from-to)374-381
Number of pages8
JournalBiochimie
Volume95
Issue number2
DOIs
Publication statusPublished - Feb 2013

Fingerprint

Harmine
Cartilage
Chondrocytes
Chondrogenesis
Degradation
Aging of materials
Connective Tissue Growth Factor
Aggrecans
Carbolines
Articular Cartilage
Alkaloids
Transgenic Mice
Libraries
Extracellular Matrix
Metabolism
Knee
Rats
Joints
Repair
Cells

Keywords

  • β-Carboline alkaloids
  • Cartilage regeneration
  • CCN2
  • Chondrocytes
  • Harmine

ASJC Scopus subject areas

  • Biochemistry

Cite this

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title = "Novel chondrogenic and chondroprotective effects of the natural compound harmine",
abstract = "A significant number of natural compounds have been shown to regulate the behavior of the cells, in collaboration with cellular proteins. CCN2/connective tissue growth factor (CTGF) has been reported to have essential roles in cartilage development, chondrocyte proliferation and differentiation as well as regulation of the extracellular matrix metabolism. Previous studies demonstrated the capability of CCN2 to regenerate surgical defects in articular cartilage of rat knee. Also, transgenic mice over-expressing cartilage-specific CCN2 were shown to be more resistant to aging-related cartilage degradation. We hypothesized that small molecules that induce CCN2 in chondrocytes could be novel candidates to increase the resistance to aging-related cartilage degradation, or even to correct cartilage degenerative changes incurred in OA. Therefore, this study screened a compound library and identified the β-carboline alkaloid harmine as a novel inducer of CCN2 in human chondrocytic HCS-2/8 cells and osteoarthritic articular chondrocytes. Harmine increased the expression of the cartilage markers aggrecan and COL2α1, as well as that of the master regulator of chondrogenesis, SOX-9. Moreover, harmine notably induced chondrogenesis of prechondrocytic ATDC5 cells in micromass cultures. The chondroprotective effect of harmine was investigated under inflammatory condition by stimulation with TNFα, and harmine was shown to ameliorate TNFα-induced decrease in expression of CCN2 and cartilage markers. These findings uncover novel chondrogenic effects of harmine and indicate harmine as a potential drug for prevention and/or repair of cartilage degradation.",
keywords = "β-Carboline alkaloids, Cartilage regeneration, CCN2, Chondrocytes, Harmine",
author = "Emilio satoshi Hara and Mitsuaki Ono and Satoshi Kubota and Wataru Sonoyama and Yasutaka Oida and Takako Hattori and Takashi Nishida and Takayuki Furumatsu and Toshihumi Ozaki and Masaharu Takigawa and Takuo Kuboki",
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AU - Hara, Emilio satoshi

AU - Ono, Mitsuaki

AU - Kubota, Satoshi

AU - Sonoyama, Wataru

AU - Oida, Yasutaka

AU - Hattori, Takako

AU - Nishida, Takashi

AU - Furumatsu, Takayuki

AU - Ozaki, Toshihumi

AU - Takigawa, Masaharu

AU - Kuboki, Takuo

PY - 2013/2

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N2 - A significant number of natural compounds have been shown to regulate the behavior of the cells, in collaboration with cellular proteins. CCN2/connective tissue growth factor (CTGF) has been reported to have essential roles in cartilage development, chondrocyte proliferation and differentiation as well as regulation of the extracellular matrix metabolism. Previous studies demonstrated the capability of CCN2 to regenerate surgical defects in articular cartilage of rat knee. Also, transgenic mice over-expressing cartilage-specific CCN2 were shown to be more resistant to aging-related cartilage degradation. We hypothesized that small molecules that induce CCN2 in chondrocytes could be novel candidates to increase the resistance to aging-related cartilage degradation, or even to correct cartilage degenerative changes incurred in OA. Therefore, this study screened a compound library and identified the β-carboline alkaloid harmine as a novel inducer of CCN2 in human chondrocytic HCS-2/8 cells and osteoarthritic articular chondrocytes. Harmine increased the expression of the cartilage markers aggrecan and COL2α1, as well as that of the master regulator of chondrogenesis, SOX-9. Moreover, harmine notably induced chondrogenesis of prechondrocytic ATDC5 cells in micromass cultures. The chondroprotective effect of harmine was investigated under inflammatory condition by stimulation with TNFα, and harmine was shown to ameliorate TNFα-induced decrease in expression of CCN2 and cartilage markers. These findings uncover novel chondrogenic effects of harmine and indicate harmine as a potential drug for prevention and/or repair of cartilage degradation.

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KW - β-Carboline alkaloids

KW - Cartilage regeneration

KW - CCN2

KW - Chondrocytes

KW - Harmine

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