Berberine induces dedifferentiation by actin cytoskeleton reorganization via phosphoinositide 3-kinase/Akt and p38 kinase pathways in rabbit articular chondrocytes

Seon Mi Yu, Hongsik Cho, Gwang Hoon Kim, Ki Wha Chung, Sung Yum Seo, Song Ja Kim

Research output: Contribution to journalArticle

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Abstract

Osteoarthritis is a nonrheumatologic joint disease characterized by progressive degeneration of the cartilage extracellular matrix. Berberine (BBR) is an isoquinoline alkaloid used in traditional Chinese medicine, the majority of which is extracted from Huang Lian (Coptis chinensis). Although numerous studies have revealed the anticancer activity of BBR, its effects on normal cells, such as chondrocytes, and the molecular mechanisms underlying its actions remain elusive. Therefore, we examined the effects of BBR on rabbit articular chondrocytes, and the underlying molecular mechanisms, focusing on actin cytoskeletal reorganization. BBR induced dedifferentiation by inhibiting activation of phosphoinositide-3(PI3)-kinase/Akt and p38 kinase. Furthermore, inhibition of p38 kinase and PI3-kinase/Akt with SB203580 and LY294002, respectively, accelerated the BBR-induced dedifferentiation. BBR also caused actin cytoskeletal architecture reorganization and, therefore, we investigated if these effects were involved in the dedifferentiation. Disruption of the actin cytoskeleton by cytochalasin D reversed the BBR-induced dedifferentiation by activating PI3-kinase/Akt and p38 kinase. In contrast, the induction of actin filament aggregation by jasplakinolide accelerated the BBR-induced dedifferentiation via PI3-kinase/Akt inhibition and p38 kinase activation. Taken together, these data suggest that BBR strongly induces dedifferentiation, and actin cytoskeletal reorganization is a crucial requirement for this effect. Furthermore, the dedifferentiation activity of BBR appears to be mediated via PI3-kinase/Akt and p38 kinase pathways in rabbit articular chondrocytes.

Original languageEnglish (US)
Pages (from-to)800-807
Number of pages8
JournalExperimental Biology and Medicine
Volume241
Issue number8
DOIs
StatePublished - Jan 1 2016

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Berberine
1-Phosphatidylinositol 4-Kinase
MAP Kinase Signaling System
Chondrocytes
Phosphatidylinositols
Actin Cytoskeleton
Actins
Phosphotransferases
Joints
Rabbits
jasplakinolide
Coptis
Chemical activation
Cytochalasin D
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Joint Diseases
Chinese Traditional Medicine
Cartilage
Alkaloids
Osteoarthritis

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Berberine induces dedifferentiation by actin cytoskeleton reorganization via phosphoinositide 3-kinase/Akt and p38 kinase pathways in rabbit articular chondrocytes. / Yu, Seon Mi; Cho, Hongsik; Kim, Gwang Hoon; Chung, Ki Wha; Seo, Sung Yum; Kim, Song Ja.

In: Experimental Biology and Medicine, Vol. 241, No. 8, 01.01.2016, p. 800-807.

Research output: Contribution to journalArticle

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