ABSTRACT
Objective:To investigate the expression of connexin-43 (Cx43) in steroid-induced osteonecrosis of femoral head and osteoblasts in rats and its regulation mechanism.Methods:The model of steroid-induced osteonecrosis of femoral head (SIONFH) of rat was established. Micro-CT and HE staining were used to observe the degree of bone trabecular destruction and the incidence of empty lacunae. The expression levels of Cx43 and PI3K/Akt signaling pathway related molecules and osteoblast-related proteins in model group and control group were detected by RT-PCT and Western blot. The osteoblast (OB) of rats was further isolated and cultured in vitro. Under treatment of dexamethasone (Dex), Cx43 expression in OB cells was detected by Western blot and immunofluorescence. Western blot was used to detect the effect of glucocorticoid (GC) on the expression of related molecules of PI3K/Akt/β-catenin signaling pathway. Akt activator (SC79) and PI3K inhibitor (LY294002) were used to study the molecular mechanism of Dex regulation on Cx43 expression in OB cells. The regulatory relationship between β-catenin and Cx43 was investigated by immunoprecipitation and small interfere RNA (siRNA) technology.Results:The model of SIONFH in rats was successfully established, which proved that Cx43 expression level in the SIONFH model group was significantly lower than that in the control group, and the expression level of Cx43 was positively correlated with the expression of PI3K/Akt signaling pathway related molecules and osteoblast-related proteins Runx2, ALP and Collagen I Type (COL). In addition, in vitro culture of isolated rat OB cells, the expression of Cx43, p-PI3K, P-Akt and β-catenin in OB cells decreased gradually as the Dex action time went on. Moreover, SC79 pretreatment could significantly reverse the inhibitory effect of GCs on Cx43 expression, while LY294002 could significantly enhance the inhibitory effect of GCs on Cx43. In addition, the immunoprecipitation results showed that β-catenin expression was closely related to Cx43 expression, and further studies showed that β-catenin-siRNA could significantly down-regulate the expression of Cx43.Conclusion:Under the action of GC, the expression level of Cx43 in bone tissue and OB cells decreased significantly, and the possible mechanism was that GCs inhibited the expression of Cx43 by inhibiting the PI3K/Akt/β-catenin signaling pathway, which laid a new theoretical foundation for the further study of the role of Cx43 in the pathogenesis of steroid-induced femoral head necrosis.
ABSTRACT
Objective:To evaluate the result of operation and gait analysis at the early stage after direct anterior approach (DAA) in total hip arthroplasty (THA).Methods: In this study,20 patients who suffered from necrosis of femoral head or developmental dysplasia of the hip were scheduled to undergo THA.The basic information and visual analogue scale (VAS) score,Harris score before and after surgery were recorded.All of the patients finished the gait analysis before the surgery and 6 weeks and 12 weeks after the surgery,the data were compared with those of normal adult people.Results: Their hospital stay after the operation was 3.3 d,the VAS score after the operation was no more than 4 points,the positions of prosthesis were satisfactory,and there was no dislocation.The gait analysis results contained step speed,stride,the range of motion (ROM) of hip and knee.The step speed before the surgery (preoperation,Pre) was 0.64 m/s,6 weeks after the surgery (6W) was 0.77 m/s,12 weeks after the surgery (12W) was 1.07 m/s,and the control group was 1.19 m/s.The stride at Pre,6W,12W,and control group were 43.15 steps/min,51.42 steps/min,55.52 steps/min,and 57.15 steps/min,respectively.The ROM of hip joint at Pre,6W,12W,and control group were 31.00°,39.62°,40.40°,and 45.67°,respectively.The ROM of knee joint at Pre,6W,12W,and control group were 50.52°,59.28°,67.29°,and 70.42°,respectively.The results of the gait analysis showed that the gait recovery after the direct anterior total hip arthroplasty was very fast and at the 12th week after surgery the gait of the patients was close to the normal adult people.Conclusion: The direct anterior approach is one of the choosable approach of the THA,and this kind of surgery has a better recovery of gait after the operation,and at the end of 12 weeks after the surgery the gait is very close to the normal adult people.But we also need more studies to prove this conclusion.