Maresin 1 enhances osteogenic potential of mesenchymal stem cells by modulating macrophage peroxisome proliferator-activated receptor-γ-mediated inflammation resolution

Inflammation resolution plays a significant role in attenuating bone injury aggravated by acute inflammation and maintaining bone homeostasis. Maresin 1 (MaR1), a specialized pro-resolving mediators (SPMs), is biosynthesised in macrophages (Mφs) that regulates acute inflammation. Strategies to accelerate the resolution of inflammation in bone repair include not only promoting vanish of acute inflammation, also improving osteogenic microenvironment. Here, previously prepared difunctional demineralized bone matrix (DBM) scaffold was used to study thoroughly the "cross-talk" between Mφs lipid metabolism and mesenchymal stem cells (MSCs) behaviors in vitro. The pro-resolving mechanism in Mφs treated with MaR1 was elaborated. Furthermore, the biological behaviors of MSCs in co-culture system were evaluated. The results indicated that MaR1 had an enhanced capability and performance in peroxisome proliferator-activated receptor-γ (PPAR-γ) activation, M2-type Mφs polarization, and lipid droplets (LDs) biogenesis in Mφs in vitro. The nuclear receptor PPAR-γ enhanced the anti-inflammatory proteins expression and the polarization of Mφs toward M2 subtype, thereby favoring the proliferation, migration, and osteogenesis of MSCs. Overall, the results verified that MaR1 facilitated MSCs behaviors by regulating PPAR-γ-mediated inflammatory response, which implied that PPAR-γ exhibited a significant role in the dialogue between MSCs behaviors and Mφs lipid metabolism.