Study on the effects of statin on growth and differentiation of cartilage

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Statin compounds are reported to activate BMP-2 gene expression and to generate the bone formation as a result. Statins are originally known to be inhibitors for HMG CoA reductase that strongly lower plasma cholesterol and triglycerides levels in human and animals and are used for the therapy of hypercholesterolemia. In this study, stains, serivastatin and pravastatin are examined for their action on growth and differentiation of cartilage.Several cDNA probes are generated from human and rabbit to examine the differentiation markers. Using these porbes, the effects of statins on primary cultures of chondrocytes and stem cells from rabbits were determined and following results were obtained.Pravastatin increased the Jevel of BMP-2 mRNA in rabbit chondrocytes for 24 h at 10^<-5> M.Serivastatin did not affect the level of BMP-2 mRNA in rabbit stem cells at 10^<-6> M, whereas it markedly increased the level of Indian hedgehog mRNA concomitantly increment of levels of PTHrP and alkaline phosphatase mRNA was observed. Calcification was observed at 5x10^<-5> M.In the course of this study, novel basic helix-loop-helix transcription factors, DEC1 and DEC2, were isolated and proved to be involved in the regulation of chondrocyte differentiation. DEC1 and DEC2 were ubiquitously expressed in various organs and exhibit multiple functions including new members of molecular clock regulation circadian rhythm of animals. The rhythmic expression of DEC1 and DEC2 were also observed in cartilage indicating the importance of rhythmic regulation of chondrocyte growth and differentiation.