Introduction: The influence of bone fracture healing in patients with chronic obstructive pulmonary disease (COPD) is unknown. It has been suggested that the pathogenesis of COPD may involve a dysfunction of the NF-E2-related factor 2 (Nrf2) signaling pathway, a defense mechanism against oxidative stress. We investigated the process of cortical bone remodeling in COPD mice by focusing on Nrf2 and the effect of sulforaphane (SFN), an Nrf2 activator, on delayed cortical bone repair.
Methods: Twelve-week-old male C57BL/6J mice were intratracheally injected with saline (C group) or PPE 0.1U (P group), and a 1.0 mm diameter drill hole was made in the distal femur at 12 weeks after the administration. All mice were sacrificed at day 14 after surgery, and the bone histomorphometry of the generating bone at the drill hole was measured, and the expression levels of Nrf2 and NQO-1 in the same area were evaluated by immunostaining. Next, half of each of the C and P groups were treated with SFN (CS, PS group) subcutaneously 5 times a week, sacrificed at day 14 after surgery, and bone tissue samples were evaluated with the same procedure.
Results: Bone histomorphometry of the generating bone at the drill hole on day 14 showed that bone volume (BV/TV), osteoblast surface (Ob.S/BS), and number of osteoblasts (Ob.N/BS) were significantly lower in the P group than in the C group, but all values were significantly higher in the PS group than in the P groups. Immunostaining showed that Nrf2 and NQO-1 protein expression was decreased in the P group compared to the C group, while the PS group showed protein expression comparable to the C group.
Conclusion: In COPD mice, there was the delayed cortical bone repair due to the impaired bone formation associated with inactivated Nrf2 signaling pathway, and SFN may improve this condition.