Mevalonate-suppressive dietary isoprenoids for bone health.

摘要: Osteoclastogenesis and osteoblastogenesis, the balancing acts for optimal bone health, are under regulation of small guanosine triphosphate-binding proteins (GTPases) including Ras, Rac, Rho Rab. The activities GTPases require post-translational modification with mevalonate-derived prenyl pyrophosphates. Mevalonate deprivation induced by competitive inhibitors 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase (e.g., statins) prevents activation GTPases, suppresses expression receptor nuclear factor kappa B (NFκB) ligand (RANKL) NFκB and, consequently, inhibits osteoclast differentiation induces apoptosis. In contrast, statin-mediated inactivation enhances alkaline phosphatase activity morphogenetic protein-2, vascular epithelial growth factor, osteocalcin in osteoblasts osteoblast proliferation differentiation. Animal studies show that statins inhibit resorption increase formation. anabolic effect other mevalonate pathway-suppressive pharmaceuticals resembles anti-osteoclastogenic bone-protective conferred dietary isoprenoids, secondary products plant metabolism. tocotrienols, vitamin E molecules HMG CoA reductase-suppressive activity, induce concomitantly suppress RANKL cyclooxygenase-2, production prostaglandin E2 NFκB. Accordingly, tocotrienols apoptosis, impacts reminiscent those statins. vivo confirm protective at nontoxic doses. Blends isoprenoids widely found fruits, vegetables, grains, herbs, spices, essential oils may synergistically osteoclastogenesis while promoting offering a novel approach to health warrants clinical studies.