“Removing Blood Stasis” Method for bone repair in steroid-induced osteonecrosis of the femoral heads / 中国组织工程研究

ABSTRACT

BACKGROUND:The pathogenesis of steroid-induced osteonecrosis of the femoral head remains unclear. Femoral head reconstruction after colapse is related to the bone remodeling due to disorder of the bone formation-absorption coupling. “Removing Blood Stasis” Method has been shown to have a positive effect on the disease in clinics. However, the mechanisms by which the “Removing Blood Stasis” Method confers bone repair after osteonecrosis remain poorly understood. OBJECTIVE:To explore the effect of “Removing Blood Stasis” Method on bone repair in rabbits with steroid-induced femoral head osteonecrosis. METHODS: Fifty New Zealand rabbits were randomly assigned into three groups normal control (n=10), model (n=20) andTaohong Siwu Decoction (n=20) groups, respectively. The steroid-induced osteonecrosis of the femoral head animal models were established by intramuscular injection of endotoxin combined with methylprednisolone (MPS). Rabbits inTaohong Siwu Decoction group were intragastricaly administered with 0.3 g/kg ofTaohong Siwu Decoction suspension after the last injection of methylprednisolone. The control and model groups were administrated by equal volume of ultrapure water for 8 consecutive weeks. High-resolution MRI and pathological determinations were used to assess the successful models. Protein expression levels of ABCB1, RUNX2, OPN, RANK, RANKL, PPAR, osteoprotegerin (OPG), vascular endothelial growth factor (VEGF) in rabbit femoral heads were detected by western blot assay. RESULTS AND CONCLUSION:(1) Hematoxylin-eosin staining showed that trabecular bone fracture, karyopyknosis, empty lacunae, necrotic bone marrow cels were seen in the model group. Empty lacunae rate in the model group was significantly different from that in the normal control group (P < 0.05). Bone formation was active and kept better trabecular morphology in theTaohong Siwu Decoction group. It suggested that “Removing Blood Stasis” Method can improve repair of necrotic area. (2) In the model group, femoral head with a wide range of low-density areas in high-resolution MRI;Taohong Siwu Decoction group showed the relatively normal shape of the femoral head with smal areas of low density. It suggested that “Removing Blood Stasis” Method can improve image changes in the necrotic area. (3) Protein expression levels of RUNX2, RANK, RANKL were significantly up-regulated but protein expression levels of ABCB1, OPG, VEGF were significantly down-regulated in the model group compared with the normal control group; whereas, they were al significantly up-regulated in theTaohong Siwu Decoction group compared with the model group, except for RANK and RANKL (P < 0.05). These results suggest that the “Removing Blood Stasis” Method can promote bone repair in steroid-induced femoral head osteonecrosis rabbits by regulating protein expressions of ABCB1, RUNX2, RANK, RANKL, OPG, and VEGF.