Department of Arts and Sciences, Faculty of Medicine, Kindai University, Osaka 589-8511, Japan.
Department of Physiology and Regenerative Medicine, Faculty of Medicine, Kindai University, Osaka 589-8511, Japan.
Int J Mol Sci. 2022 Jan 1;23(1):478. doi: 10.3390/ijms23010478.
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.
糖皮质激素延迟骨折愈合并导致骨质疏松。然而，糖皮质激素延迟骨修复的机制尚未阐明。纤溶酶原激活物抑制剂-1（PAI-1）是纤溶酶原激活物的主要抑制剂，也是一种调节代谢的脂肪细胞因子。我们在此使用腹腔内给予地塞米松（Dex）的 PAI-1 缺陷型雌性小鼠研究了巨噬细胞在糖皮质激素诱导的股骨损伤后骨修复延迟中的作用。Dex 在股骨损伤后两天显着减少了损伤部位的 F4/80 阳性巨噬细胞数量。它还减弱了野生型和 PAI-1 缺陷型小鼠骨髓中造血干细胞数量因骨损伤而减少的情况。PAI-1 缺陷显着削弱了 Dex 诱导的骨损伤后两天损伤部位巨噬细胞数量和巨噬细胞集落刺激因子（M-CSF）mRNA 水平的降低。它还显着改善了 Dex 对损伤部位巨噬细胞吞噬作用的抑制作用。总之，我们在本研究中证明，Dex 通过小鼠中的 PAI-1 和 M-CSF 在股骨损伤后早期骨修复过程中减少了损伤部位的巨噬细胞数量。
