Development of non-traumatic osteonecrosis of the femoral head requires toll-like receptor 7 and 9 stimulations and is boosted by repression on nuclear factor kappa B in rats

Okazaki, Shunichiro; Nagoya, Satoshi; Matsumoto, Hiroshi; Mizuo, Keisuke; Sasaki, Mikito; Watanabe, Satoshi; Yamashita, Toshihiko; Inoue, Hiromasa

Inhibition of IRF7 by BAY11-7082 Interferes with the Development of ONFH As described above, we observed changes in transcription factor activity in the liver 24 h after MPSL treatment. We hypothesized that this change might trigger the onset of primary corticosteroid-induced ONFH, and a repression in IRF7 activity by the use of an inhibitor could interfere with the development of ONFH in spite of the simultaneous repression in NF-kB activity, resulting from MPSL treatment. To clarify this hypothesis, the Imiquimod þ BAY11 þ MPSL (3 Â n ¼ 10 and n ¼ 6 receiving 1, 3, 5, or 10 mg/kg BAY11-7082, respectively) groups were killed 14 days after MPSL treatment. Table 3 shows the incidence of ONFH in each group. Co-administration of BAY11-7082 with MPSL was found to interfere with the development ONFH in a Figure 2 Histological appearance of the femoral head affected by osteonecrosis. Panels show hematoxylin and eosin-stained femurs. Typical images from the Imiquimod þ Saline group with ONFH (a) and without ONFH (b) are shown. The diffuse presence of empty lacunae and pyknotic osteocytic nuclei in the bone trabeculae accompanied by bone marrow cell necrosis was also observed in the femoral head of rats with ONFH (a). Scale bar: 100 mm.