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.