Bone induction using hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors

Abstract

ABSTRACT Objectives. The search of a non-toxic material to replace bone remains a big challenge for scientists. Previous studies examined more than 30 000 compounds from a collection of natural products and identified that statins, commonly used hydroxymethylglutaryl coenzyme A reductase inhibitors (HMGRIs), increased expression of the morphogenetic protein (BMP)-2 gene. This article summarizes our research into the use of HMGRIs to induce bone formation. Methods. Twenty-four bone defects from 12 New Zealand White rabbits were divided into four study groups (negative control, control, statin, and naringin) for quantitative assessment of new bone formation with HMGRIs, and 30 bone defects from another 15 New Zealand White rabbits divided into two groups (control and statin) for study of early healing pattern of HMGRI-induced osteogenesis. Results. Two hundred and ninety-eight percent and 490% more new bone were respectively formed by statin and naringin both mixed with a collagen carrier comparing with defects grafted with the carrier alone. Using immunolocalization studies to look into the mechanisms of the HMGRI-induced osteogenesis, it was shown that for early healing defects grafted with statin, the vascular endothelial growth factor, BMP-2, core-binding factor alpha 1 were expressed 1 day earlier than those grafted with the carrier alone. Conclusion. Statin and naringin in collagen matrix carriers had the effect of increasing new bone formation locally and may be useful as a bone graft material.