Maresin 1 resolves aged-associated macrophage inflammation to improve bone regeneration.
Inflammaging is associated with poor tissue regeneration observed in advanced age. Specifically, protracted inflammation after acute injury has been associated with decreased bone fracture healing and increased rates of nonunion in elderly patients. Here, we investigated the efficacy of using Maresin 1 (MaR1), an omega-3 fatty acid-derived pro-resolving agent, to resolve inflammation after tibial fracture injury and subsequently improving aged bone healing. Aged (24-month-old mice) underwent tibial fracture surgery and were either treated with vehicle or MaR1 3 days after injury. Fracture calluses were harvested 7 days, 14 days, 21 days, and 28 days after injury to investigate inflammatory response, cartilage development, bone deposition, and mechanical integrity, respectively. Healing bones from MaR1-treated mice displayed decreased cartilage formation and increased bone deposition which resulted in increased structural stiffness and increased force to fracture in the later stages of repair. In the early stages, MaR1 treatment decreased the number of pro-inflammatory macrophages within the fracture callus and decreased the level of inflammatory biomarkers in circulation. In tissue culture models, MaR1 treatment of bone marrow-derived macrophages from aged mice protected cells form a pro-inflammatory phenotype and induced an anti-inflammatory fate. Furthermore, the secretome of MaR1-treated bone marrow-derived macrophages was identified as osteoinductive, enhancing osteoblast differentiation of bone marrow stromal cells. Our findings here identify resolution of inflammation, and MaR1 itself, to be a point of intervention to improve aged bone healing.
['Huang|Rong|R|', 'Vi|Linda|L|', 'Zong|Xiaohua|X|', 'Baht|Gurpreet S|GS|']
D000375:Aging D000818:Animals D000893:Anti-Inflammatory Agents D001861:Bone Regeneration D002454:Cell Differentiation D002478:Cells, Cultured D004281:Docosahexaenoic Acids D005260:Female D017102:Fracture Healing D007249:Inflammation D008264:Macrophages D008297:Male D059630:Mesenchymal Stem Cells D051379:Mice D013978:Tibial Fractures
macrophage bone inflammaging fracture healing osteoblast