Knockout of formyl peptide receptor 1 reduces osteogenesis and bone healing

Abstract

AimsFormyl peptide receptor 1 (FPR1), from a G-protein coupled receptor family, was previously well-characterized in immune cells. But the function of FPR1 in osteogenesis and fracture healing was rarely reported. This study, using the FPR1 knockout (KO) mouse, is one of the first studies that try to investigate FPR1 function to osteogenic differentiation of bone marrow-derived stem cells (BMSCs) in vitro and bone fracture healing in vivo. Materials and methodsPrimary BMSCs were isolated from both FPR1 KO and wild type (WT) mice. Cloned mouse BMSCs (D1 cells) were used to examine role of FoxO1 in FPR1 regulation of osteogenesis. A closed, transverse fracture at the femoral midshaft was created to compare bone healing between KO and WT mice. Biomechanical and structural properties of femur were compared between healthy WT and KO mice. Key findingsFPR1 expression increased significantly during osteogenesis of both primary and cloned BMSCs. Compared to BMSCs from FPR1 KO mice, WT BMSCs displayed considerably higher levels of osteogenic markers as well as mineralization. Osteogenesis by D1 cells was inhibited by either an FPR1 antagonist cFLFLF or a specific inhibitor of FoxO1, AS1842856. In addition, the femur from WT mice had better biomechanical properties than FPR1 KO mice. Furthermore, bone healing in WT mice was remarkably improved compared to FPR1 KO mice analyzed by X-ray and micro-CT. SignificanceThese findings indicated that FPR1 played a vital role in osteogenic differentiation and regenerative capacity of fractured bone, probably through the activation of FoxO1 related signaling pathways.