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Objective:To explore the molecular mechanism for bone mass loss caused by staphylococcus aureus infection.Methods:Thirty 8-week-old male C57BL/6 mice were randomly divided into 3 groups ( n=10): control, infection and infection+JAK inhibitor (JAKi) ones. The mice were killed 2 weeks later for sampling from the femur and tibia. Micro-CT reconstruction was performed for analyses of BV/TV, Tb.N, Tb.Th and Tb.Sp to detect changes in bone mass; OCN immunohistochemistry and Goldner's trichrome staining were used to quantify osteoblasts; TRAP staining was used to quantify osteoclasts; the GSE166522 data set was downloaded and analyzed to explore the relationships between staphylococcus aureus infection and bone cell senescence and JAK/STAT pathway. Senescence β-Galactosidase staining, Osterix and P16 immunofluorescence colocalization were used to observe the changes in number of senescent cells. Results:MicroCT results showed a statistically significant difference in the loss of cancellous bone in the target area in the infection group compared with the control group ( P<0.05). The results of osteocalcin immunohistochemistry and Goldner's trichrome staining indicated that the number of osteoblasts in the infection group was significantly reduced ( P<0.05). TRAP staining indicated no significant difference in the number of osteoclasts between the infection and control groups ( P>0.05). Bioinformatics analysis found that staphylococcus aureus infection caused bone cell senescence and the JAK/STAT pathway was activated after the infection. Senescence β-Galactosidase staining suggested that senescent cells increased in the infection group compared with the control group. The number of Osterix and P16 positive senescent osteoprogenitor cells in the infection group was increased significantly compared with the control group. The number of senescent osteoprogenitor cells in the infection+JAKi group was significantly reduced and the bone loss was partially reversed after treatment of JAK inhibitor, compared with the infection group. Conclusion:Staphylococcus aureus may induce osteoprogenitor cell senescence through the JAK/STAT pathway and eventually lead to bone mass loss.
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Objective To compare the effects of fixations with dynamic hip screw (DHS),percutaneous compression plate (PCCP) and proximal femoral nail anti-rotation (PFNA) for treatment of intertrochanteric femoral fractures with paries medialis defect.Methods We reviewed the 82 patients with femoral intertrochanteric fracture and paries medialis defect who had been treated at our department from January 2011 to July 2016.They were 42 men and 40 women,aged from 27 to 91 years (average,73.0 years).According to the AO classification,72 cases belonged to type 31-A2.2,10 to type 31-A2.3.Of them,9 cases were treated with DHS,17 cases with PCCP and 56 cases with PFNA-1].The 3 groups were compared in terms of intraoperative blood loss,blood infusion,fluid infusion,operation duration,time for fracture union,postoperative complications and Functional Recovery Score (FRS) of the hip 12 months after operation.Results The fluid infusion [1,100 (850,1,100) mL] and intraoperative blood loss [60 (5,100) mL] in the PCCP group were significantly less than in the PFNA group [1,100 (1,000,1,700) mL and 150 (50,300) mL] and the operation duration (91.4 ± 29.2 min) in the former was significantly shorter than in the latter [121 (85,185) min] (P ＜ 0.05).No significant difference was found between the 3 groups in blood infusion (P ＞ 0.05).Of the patients,57 (8 DHS,12 PCCP and 37 PFNA ones) were followed up for an average of 47 months (from 15 to 85 months).There were no statistically significant differences between the 3 groups in time for fracture union,complications,or average FRS score of the hip 12 months after operation (P ＞ 0.05).Conclusions For unstable intertrochanteric fractures with paries medialis defect,it is not clear that intramedullary nails are superior to extramedullary fixation.Intramedullary nails like PFNA may be suggested for patients with better preoperative conditions while extramedullary fixation like PCCP suggested for those with poor general conditions.
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Objective To apply iTRAQ technology to observe changes in protein expression group in the process of inducing C2C12 cells differentiation towards osteoblast by BMP-2.Methods The myoblast C2C12 cells were seeded in BMP-2 induced differentiation system for differentiation induction.In the 7th day,differentiation protein was extracted and labeled with iTRAQ reagent.Then,mass spectrometric detection,data analysis of differentially expressed proteins,and analysis of biological information were carried out.Results 23 significantly differentially expressed protein spots were screened by BMP-2-induced myoblast C2C12 differentiated cell protein expression profile analysis,where the protein was labeled with iTRAQ reagent.8 protein points were up-regulated,and 15 protein points were down-regulated.Trend classification found that the above differential protein had differential expression in each period of C2C12 cell osteogenic differentiation (1-7 days).Part of up-regulated protein in the early differentiation period showed high expression level;part of up-regulated protein in the late differentiation period showed high expression level;similarly,part of down-regulated protein in the early differentiation period presented low expression level;part of down-regulated protein in the late differentiation period showed low expression level.Preliminary identification showed SERCA3,Cytochrome bS,S100A4,ATPase inhibitor and ATPIF1 presented dynamic changes,which suggests that these proteins may be related to inducing osteogenic differentiation mechanism.Conclusion The results of differential protein expression trend show the necessity of full monitoring of C2C 12 cells osteogenic differentiation and indicate that iTRAQ technology is an effective method of studying protein changes of cellular molecule.Five proteins including SERCA3,Cytochrome b5,S100A4,ATPase inhibitor and ATPIF1 can be used as candidate targets for osteogenic differentiation mechanism research.