Role of macrophages and plasminogen activator inhibitor-1 in delayed bone repair in diabetic female mice

• Published in: Endocrinology (Philadelphia) Vol. 159; no. 4; pp. 1875 - 1885
• Main Authors: Shimoide, Takeshi, Kawao, Naoyuki, Tamura, Yukinori, Okada, Kiyotaka, Horiuchi, Yoshitaka, Okumoto, Katsumi, Kurashimo, Shinji, Ishida, Masayoshi, Tatsumi, Kohei, Matsuo, Osamu, Kaji, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States 01.04.2018
• ISSN: 1945-7170; 1945-7170
• DOI: 10.1210/en.2018-00085

Delayed fracture healing is a significant clinical problem among various complications in diabetic patients. However, the details in the mechanisms of diabetic delayed bone repair have still remained unknown. Here, we investigated the roles of macrophages in diabetic delayed bone repair after femoral bone injury using streptozotocin (STZ)-treated or plasminogen activator inhibitor-1 (PAI-1)-deficient female mice. STZ treatment significantly decreased the numbers of F4/80-positive cells (macrophages), but not Gr-1-positive cells (neutrophils), at the damaged site on day 2 after femoral bone injury in mice. It significantly decreased the mRNA levels of macrophage colony-stimulating factor, inducible nitric oxide synthase (iNOS), interleukin (IL)-6 and CD206 at the damaged site on day 2 after bone injury. Moreover, STZ treatment attenuated a decrease in the number of hematopoietic stem cells in bone marrow from damaged femurs induced by bone injury. On the other hand, PAI-1 deficiency significantly attenuated a decrease in the number of F4/80+ cells induced by STZ treatment at the damaged site on day 2 after bone injury in mice. PAI-1 deficiency did not affect the mRNA levels of iNOS and IL-6 in F4/80- and CD11b-double positive cells from the bone marrow of the damaged femurs decreased by diabetic state in mice. PAI-1 deficiency significantly attenuated the phagocytosis of macrophages at the damaged site suppressed by diabetic state. In conclusion, we demonstrated that type 1 diabetic state decreases accumulation and phagocytosis of macrophages at the damaged site during the early bone repair process after femoral bone injury through PAI-1 in female mice.