Abstract
Glucocorticoids delay fracture healing and induce osteoporosis. However, the mechanisms by which glucocorticoids delay bone repair have yet to be clarified. Plasminogen activator inhibitor-1 (PAI-1) is the principal inhibitor of plasminogen activators and an adipocytokine that regulates metabolism. We herein investigated the roles of macrophages in glucocorticoid-induced delays in bone repair after femoral bone injury using PAI-1-deficient female mice intraperitoneally administered with dexamethasone (Dex). Dex significantly decreased the number of F4/80-positive macrophages at the damaged site two days after femoral bone injury. It also attenuated bone injury-induced decreases in the number of hematopoietic stem cells in bone marrow in wild-type and PAI-1-deficient mice. PAI-1 deficiency significantly weakened Dex-induced decreases in macrophage number and macrophage colony-stimulating factor (M-CSF) mRNA levels at the damaged site two days after bone injury. It also significantly ameliorated the Dex-induced inhibition of macrophage phagocytosis at the damaged site. In conclusion, we herein demonstrated that Dex decreased the number of macrophages at the damaged site during early bone repair after femoral bone injury partly through PAI-1 and M-CSF in mice.
Highlights
IntroductionGlucocorticoids regulate numerous physiological processes [1,2]
Published: 1 January 2022Glucocorticoids regulate numerous physiological processes [1,2]
We previously reported that plasminogen activator inhibitor-1 (PAI-1), an inhibitor of plasminogen activators, contributed to delayed bone repair and osteopenia induced by streptozotocin in female diabetic mice [20,21,22]
Summary
Glucocorticoids regulate numerous physiological processes [1,2]. They have been widely used to treat chronic inflammatory diseases due to their potent anti-inflammatory effects [3,4]. The inflammatory, restoration, and bone remodeling phases, are included in the bone repair process after bone injury or fractures [9]. Exclusion of cell debris and damaged cells, the release of cytokines, or growth factors, vessel formation, and tissue repair are some of the actions of macrophages in bone repair [10]. Regarding the roles of macrophages in bone, extensive evidence suggests crucial roles for bone-specific macrophages, osteomacs, in osteoblastic bone formation and fracture healing [11,12,13,14].
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