A strategy for promoting bone regeneration by inducible expression of 15-LOX-1

Repairing large bone defects is a major orthopaedic problem, with current treatments being constrained by the regenerative capacity of human tissue. Current methods for repairing bone defects include osteogenesis, osteoconduction, osteoinduction, and tissue engineering; however, the cumulative effect of these methods is, as of yet, rather unsatisfactory. Recent research has demonstrated that knockout of the cell cycle inhibitor p21, which works as a switch to control regenerative capacity, can promote cell proliferation and appendage regeneration. The enzyme 15-lipoxygenase type 1 (15-LOX-1), which is involved in arachidonic and linoleic acid metabolism, has the potential to down-regulate the expression of p21. Therefore, we hypothesise that the construction of a new bone substitute that expresses 15-LOX-1 locally will promote osteoblast proliferation through inhibition of p21, resulting in an effective and inducible method for promoting bone regeneration. (C) 2012 Elsevier Ltd. All rights reserved.