title: Berberine promotes proliferation of sodium nitroprusside-stimulated rat chondrocytes and osteoarthritic rat cartilage via Wnt/β-catenin pathway.
abstract: Berberine chloride (BBR) is an isoquinoline derivative alkaloid isolated from medicinal herbs, including Coptis chinensis and Berberis aristate. This compound plays significant roles in the treatment of osteoarthritis (OA). The purpose of this study was to investigate the effects of BBR on the proliferation of sodium nitroprusside (SNP)-stimulated chondrocytes in vitro, the articular cartilage in a rat OA model, as well as to discuss the molecular mechanisms underlying these effects. In vitro, we demonstrated that BBR led to cell proliferation, increased the cell population in S-phase and decreased that in G0/G1-phase; moreover, the F-actin remodeling in SNP-stimulated chondrocytes were prevented. In addition, BBR markedly up-regulated β-catenin, c-Myc, and cyclin D1 expression of genes and proteins, and down-regulated glycogen synthase kinase-3β (GSK-3β) and matrix metalloproteinase-7 (MMP-7) expression. Notably, inhibition of the Wnt/β-catenin pathway by XAV939 partially blocked these effects. The in vivo results suggested that BBR promoted β-catenin protein level and enhanced proliferating cell nuclear antigen (PCNA) expression in osteoarthritic rat cartilage. In conclusion, these findings indicate that BBR promotes SNP-stimulated chondrocyte proliferation by promoting G1/S phase transition and synthesis of PCNA in cartilage through activation of Wnt/β-catenin signaling pathway.
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China; Department of Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China; Laboratory of Clinical Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China; Laboratory of Clinical Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Tao
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China; Laboratory of Clinical Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China; Laboratory of Clinical Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Deng
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.affiliation: Department of Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China; Laboratory of Clinical Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
authors.forename: Shaoqiang
authors.initials: S
authors.lastname: Xia
authors.affiliation: Department of Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China; Laboratory of Clinical Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China; Department of Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China. Electronic address: liusqrm@163.com.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D009599:Nitroprusside / Q000009:adverse effects*; D010003:Osteoarthritis / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc; C491192:Tcf4 protein, rat; D000073940:Transcription Factor 4; D014157:Transcription Factors; D001599:Berberine; D019938:Cyclin D1; D009599:Nitroprusside; D000071679:Glycogen Synthase Kinase 3 beta
keywords: Berberine; Berberine chloride (PubChem CID: 12456); Chondrocyte; Osteoarthritis; Proliferation; Sodium nitroprusside; Wnt/β-catenin