title: Fracture healing and lipid mediators.
abstract: Lipid mediators regulate bone regeneration during fracture healing. Prostaglandins and leukotrienes are well-known lipid mediators that regulate inflammation and are synthesized from the Ω-6 fatty acid, arachidonic acid. Cyclooxygenase (COX-1 or COX-2) and 5-lipoxygenase (5-LO) catalyze the initial enzymatic steps in the synthesis of prostaglandins and leukotrienes, respectively. Inhibition or genetic ablation of COX-2 activity impairs fracture healing in animal models. Genetic ablation of COX-1 does not affect the fracture callus strength in mice, suggesting that COX-2 activity is primarily responsible for regulating fracture healing. Inhibition of cyclooxygenase activity with nonsteroidal anti-inflammatory drugs (NSAIDs) is performed clinically to reduce heterotopic ossification, although clinical evidence that NSAID treatment impairs fracture healing remains controversial. In contrast, inhibition or genetic ablation of 5-LO activity accelerates fracture healing in animal models. Even though prostaglandins and leukotrienes regulate inflammation, loss of COX-2 or 5-LO activity appears to primarily affect chondrogenesis during fracture healing. Prostaglandin or prostaglandin analog treatment, prostaglandin-specific synthase inhibition and prostaglandin or leukotriene receptor antagonism also affect callus chondrogenesis. Unlike the Ω-6-derived lipid mediators, lipid mediators derived from Ω-3 fatty acids, such as resolvin E1 (RvE1), have anti-inflammatory activity. In vivo, RvE1 can inhibit osteoclastogenesis and limit bone resorption. Although Ω-6 and Ω-3 lipid mediators have clear-cut effects on inflammation, the role of these lipid mediators in bone regeneration is more complex, with apparent effects on callus chondrogenesis and bone remodeling.
authors.affiliation: Department of Biochemistry & Molecular Biology, New Jersey Medical School and Graduate School of Biomedical Sciences, Rutgers, the State University of New Jersey , Newark, NJ, USA.
authors.forename: J Patrick
authors.initials: JP
authors.lastname: O'Connor
authors.affiliation: Department of Biochemistry & Molecular Biology, New Jersey Medical School and Graduate School of Biomedical Sciences, Rutgers, the State University of New Jersey , Newark, NJ, USA.
authors.forename: Michaele B
authors.initials: MB
authors.lastname: Manigrasso
authors.affiliation: Department of Biochemistry & Molecular Biology, New Jersey Medical School and Graduate School of Biomedical Sciences, Rutgers, the State University of New Jersey , Newark, NJ, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Kim
authors.affiliation: Department of Biochemistry & Molecular Biology, New Jersey Medical School and Graduate School of Biomedical Sciences, Rutgers, the State University of New Jersey , Newark, NJ, USA.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Subramanian