title: Berberine induces dedifferentiation by actin cytoskeleton reorganization via phosphoinositide 3-kinase/Akt and p38 kinase pathways in rabbit articular chondrocytes.
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.
authors: Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongjudaehakro 56, Gongju 32588, Republic of Korea.
authors: Seon-Mi
authors: SM
authors: Yu
authors: Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, TN 38119, USA Veterans Affairs Medical Center, Memphis, TN 38117, USA.
authors: Hongsik
authors: H
authors: Cho
authors: Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongjudaehakro 56, Gongju 32588, Republic of Korea.
authors: Gwang-Hoon
authors: GH
authors: Kim
authors: Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongjudaehakro 56, Gongju 32588, Republic of Korea.
authors: Ki-Wha
authors: KW
authors: Chung
authors: Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongjudaehakro 56, Gongju 32588, Republic of Korea.
authors: Sung-Yum
authors: SY
authors: Seo
authors: Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongjudaehakro 56, Gongju 32588, Republic of Korea ksj85@kongju.ac.kr.
authors: Song-Ja
authors: SJ
authors: Kim
mesh_terms: D000199:Actins / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D015153:Blotting, Western; D054337:Cell Dedifferentiation / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D007596:Joints / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008856:Microscopy, Fluorescence; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D000199:Actins; D001599:Berberine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Berberine; PI3-kinase/Akt; actin cytoskeleton reorganization; chondrocytes; p38 kinase