Hepatocyte growth factor improves bone regeneration via the bone morphogenetic protein­2­mediated NF­κB signaling pathway.

Bone regeneration is an important process associated with the treatment of osteonecrosis, which is caused by various factors. Hepatocyte growth factor (HGF) is an active biological factor that has multifunctional roles in cell biology, life sciences and clinical medicine. It has previously been suggested that bone morphogenetic protein (BMP)­2 exerts beneficial roles in bone formation, repair and angiogenesis in the femoral head. The present study aimed to investigate the benefits and molecular mechanisms of HGF in bone regeneration. The viability of osteoblasts and osteoclasts were studied in vitro. In addition, the expression levels of tumor necrosis factor (TNF)­α, monocyte chemotactic protein (MCP)­1, interleukin (IL)­1 and IL­6 were detected in a mouse fracture model following treatment with HGF. The expression and activity of nuclear factor (NF)­κB were also analyzed in osteocytes post­treatment with HGF. Histological analysis was used to determine the therapeutic effects of HGF on mice with fractures. The migration and differentiation of osteoblasts and osteoclasts were investigated in HGF­incubated cells. Furthermore, angiogenesis and BMP­2 expression were analyzed in the mouse fracture model post­treatment with HGF. The results indicated that HGF regulates the cell viability of osteoblasts and osteoclasts, and also balanced the ratio between osteoblasts and osteoclasts. In addition, HGF decreased the serum expression levels of TNF­α, MCP­1, IL­1 and IL­6 in experimental mice. The results of a mechanistic analysis demonstrated that HGF upregulated p65, IκB kinase­ß and IκBα expression in osteoblasts from experimental mice. In addition, the expression levels of vascular endothelial growth factor, BMP­2 receptor, receptor activator of NF­κB ligand and macrophage colony­stimulating factor were upregulated by HGF, which may effectively promote blood vessel regeneration, and contribute to the formation and revascularization of tissue­engineered bone. Furthermore, HGF promoted BMP­2 expression and enhanced angiogenesis at the fracture location. These results suggested that HGF treatment may significantly promote bone regeneration in a mouse fracture model. In conclusion, these results indicated that HGF is involved in bone regeneration, angiogenesis and the balance between osteoblasts and osteoclasts, thus suggesting that HGF may be considered a potential agent for the treatment of fractures via the promotion of bone regeneration through regulation of the BMP­2­mediated NF­κB signaling pathway.

Effect of semisynthetic extracellular matrix-like hydrogel containing hepatocyte growth factor on repair of femoral neck defect in rabbits.

Using tissue engineering technology research to develop organized artificial bone, then repair bone defect. This work aims to investigate the role of semisynthetic extracellular matrix-like hydrogel (sECMH) containing hepatocyte growth factor (HGF) on repair of femoral neck defect in rabbits. 18 New Zealand rabbits were used in this study. According to autologous paired comparison method, the left and right sides of rabbit were used as control and experimental side, respectively. The models of bilateral femoral neck bone defect were established. In experimental side, sECMH containing HGF was implanted in the defect area. In control side, no material was implanted in the defect area. At the 2nd, 4th and 8th week after surgery, the gross observation, histological examination and molybdenum target (Mo-target) X-ray examination were performed on the specimens to study the repair of femoral neck defect. In gross observation, there was no macroscopic difference of femoral neck specimen between the 2nd and 4th postoperative week. At the 8th week, the defect orifice was closed with immature cortical bone, with unblocked marrow cavity. HE staining results showed that, at the 4th week, there were more new vessels in defect area of experimental side, compared with control side. At the 8th week, in experimental side there was immature cortical bone connecting the fracture end in defect area, with visible bone marrow cells. Mo-target X-ray examination found that, at the 8th week, the bone tissue repair in experimental side was better than control side. As a new drug delivery system, sECMH containing HGF has good application prospect in bone tissue repair.

Analysis of factors affecting the prognosis of neonatal cholestasis.

This study aims to analyse the risk factors affecting prognosis of cholestasis in newborns. A four-year prospective cohort study was carried out. Neonates with cholestasis were enrolled. The diagnosis of neonatal cholestasis was based on jaundice in the newborn period, direct bilirubin > 2 mg/dl, discoloured stool and elevated liver enzymes. Liver function tests were consecutively monitored weekly during the first month and then monthly until the disease was under control. All cases received oral ursodeoxycholic acid and internal medicine comprehensive treatment. No invalid case was recorded. According to the efficacy of the treatment, all cases were divided into two groups: cure group (group A; n = 69) and improved group (group B; n = 5). The clinical data of the two groups were compared. Selected patient factors were analysed to determine the risk factors affecting the prognosis of cholestasis in newborns. The serum total bilirubin and direct bilirubin levels in group B were significantly higher than those in group A (P < 0.05). A strong linear correlation was detected between the level of direct bilirubin (or total bile acid) and the duration of the disease (r > 0.5, P < 0.05). The curative effects on neonatal cholestasis and bacterial infection, cytomegalovirus (CMV) infection, venous nutrition (> 7 d) and preterm birth were closely related. The above factors were also independent risk factors affecting the prognosis of neonatal cholestasis. The direct bilirubin or total bile acid level was closely related to the duration of neonatal cholestasis. Bacterial infection, CMV infection, venous nutrition (> 7 d) and preterm birth were significant risk factors affecting the prognosis of neonatal cholestasis.