title: Lovastatin promotes redifferentiation of human nucleus pulposus cells during expansion in monolayer culture.
abstract: To acquire the capacities for matrix production and preservation of an expanded volume within a damaged intervertebral disc (IVD), cells isolated from human nucleus pulposus (NP) tissues must undergo several passages in monolayer culture. However, chondrocytes and IVD cells in monolayer culture undergo "dedifferentiation," characterized by decreased synthesis of type II collagen and increased synthesis of type I collagen, thereby compromising the properties of regenerative tissues. The present study was undertaken to ascertain whether lovastatin reverses "dedifferentiation" of human NP cells during monolayer expansion. Expression of genes encoding type II collagen and transcription factor SOX9 in these cells was upregulated by lovastatin, with maximal stimulations observed at 5 µM, whereas type I collagen gene expression was suppressed by the drug, with maximal inhibitions observed at 5-10 µM. At lovastatin concentrations ≥1 µM, expression of genes encoding the bone morphogenetic proteins BMP-2 and BMP-7 was also significantly enhanced. Furthermore, the number of NP cells exhibiting a rounded shape and positive staining for S-100 protein and type II collagen protein increased during treatment with lovastatin. These findings strongly support the induction by lovastatin of "redifferentiation" of human NP cells during their expansion in monolayer culture.
authors.affiliation: Department of Orthopedics, National Taiwan University Hospital Yun-Lin Branch, no. 579 Yunlin Road sec. 2, Douliou City, Yunlin, Taiwan.
authors.forename: Ming-Hsiao
authors.initials: MH
authors.lastname: Hu
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Hung
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Yang
authors.forename: Yuan-Hui
authors.initials: YH
authors.lastname: Sun
authors.forename: Tiffany Ting-Fang
authors.initials: TT
authors.lastname: Shih
authors.forename: Feng-Huei
authors.initials: FH
authors.lastname: Lin
mesh_terms: D000328:Adult; D053674:Aggrecans / Q000235:genetics; D018929:Cell Culture Techniques; D054337:Cell Dedifferentiation / Q000187:drug effects*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D024043:Collagen Type II / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007403:Intervertebral Disc / Q000166:cytology*; D008148:Lovastatin / Q000494:pharmacology*; D055758:SOX9 Transcription Factor / Q000235:genetics; D055815:Young Adult
chemical_list: D053674:Aggrecans; D024042:Collagen Type I; D024043:Collagen Type II; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D055758:SOX9 Transcription Factor; D008148:Lovastatin