Lovastatin promotes redifferentiation of human nucleus pulposus cells during expansion in monolayer culture.
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.
Hu
Ming-Hsiao
MH
Department of Orthopedics, National Taiwan University Hospital Yun-Lin Branch, no. 579 Yunlin Road sec. 2, Douliou City, Yunlin, Taiwan.
Hung
Li-Wei
LW
Yang
Shu-Hua
SH
Sun
Yuan-Hui
YH
Shih
Tiffany Ting-Fang
TT
Lin
Feng-Huei
FH
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
D053674:Aggrecans; D024042:Collagen Type I; D024043:Collagen Type II; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D055758:SOX9 Transcription Factor; D008148:Lovastatin