Hydroxylated fullerene promotes fracture healing in ovariectomized combined type 2 diabetic mice

Abstract

Background: The aim of this investigation was to assess the interventional role of hydroxylated fullerene in this model by histological, imaging, and biomechanical means in order to inform the treatment of fracture healing in a population of menopausal women with type 2 diabetes mellitus (T2DM). Methods: Sixty-four female 8-week-old C57BL/6 mice were randomly divided into four groups: fracture (F), OVX + fracture (OF), T2DM + OVX + fracture (DOF), and hydroxylated fullerene-treated DOF (DOFF). A closed fracture was established in the right tibia of each mouse, which was performed 8 weeks after undergoing ovariectomy (OVX) in the OF, DOF, and DOFF groups. Hydroxylated fullerene (5 mg/kg, every two days) was administered intraperitoneally to the DOFF group starting the day after fracture. The right tibias were collected at 7 and 28 days post-fracture. Results: The systemic administration of hydroxylated fullerene significantly increased the microstructural parameters of the callus (including bone volume fraction [BV/TV] and connectivity density [Conn.D]), promoted BMP-2 expression and inhibited TNF-α expression in the callus at 7 days post-fracture, and increased the expression of type I collagen (COL1) and osteocalcin (OCN) in the callus at 28 days post-fracture. Conclusion: Hydroxylated fullerene may improve fracture healing in this diabetic mouse model by reducing the inflammatory response and promoting osteogenesis. These results suggest that hydroxylated fullerene may act as a therapeutic agent for fracture healing.