1.Regulation of Toll-like receptors on function of osteoblasts and osteoclasts
Xin WANG ; Jinyong HUANG ; Mijiti WUBULIKASIMU ; Zengru XIE
Chinese Journal of Tissue Engineering Research 2024;28(12):1931-1936
BACKGROUND:Toll-like receptors are an important class of pattern recognition receptors that have important functions in pathogen immunity and cytokine synthesis by recognizing specific molecular patterns.Previous studies have found that different types of bone tissue cells also express Toll-like receptors.Activation or inhibition of Toll-like receptors can have significant effects on osteoblast and osteoclast function through multiple pathways. OBJECTIVE:To summarize the expression and action pathways of Toll-like receptors in osteoblasts and osteoclasts,in order to further elucidate the biological mechanisms involved in the regulation of Toll-like receptors under physiological and pathological conditions. METHODS:Relevant literature was retrieved from databases such as PubMed and CNKI as of December 2022.The Chinese and English search terms included"Toll-like receptor,osteoblast,osteoclast,mesenchymal stem cells,macrophage,cytokine,signaling pathway".According to the research needs,the corresponding criteria were established to screen the final literature. RESULTS AND CONCLUSION:(1)Toll-like receptors could directly regulate osteoblast and osteoclast differentiation through the activation of related signaling pathways.(2)Toll-like receptor activation induces cytokine production and exerts regulatory effects.(3)Toll-like receptor activation can affect the survival and migration ability of osteoblasts and osteoclasts.(4)Toll-like receptors in osteoblasts and osteoclasts are activated in certain diseases and pathological settings and are involved in intercellular interactions.
2.Regulation of bone tissue cells by tumor necrosis factor-alpha
Xin WANG ; Mijiti WUBULIKASIMU ; Jinyong HUANG ; Zengru XIE
Chinese Journal of Tissue Engineering Research 2024;28(21):3400-3406
BACKGROUND:Tumor necrosis factor-α is a broadly acting inflammatory cytokine that plays an important role in the immune inflammatory response of the body.The current study concluded that tumor necrosis factor-α has significant biological effects on a variety of bone tissue cells. OBJECTIVE:To summarize the expression and action pathways of tumor necrosis factor-α in osteoblastic and osteoclastic cells to further elucidate the regulatory role of tumor necrosis factor-α on bone tissue cells. METHODS:PubMed and CNKI were searched until March 2023,and the Chinese search terms included"tumor necrosis factor α,osteoblast,osteoclast,osteoclast,osteoprogenitor";the English search terms included"TNF-α,osteoblast,osteoclast,osteocyte,osteoprogenitor cell".The corresponding criteria were established according to the research needs,and the final literature was screened.Finally,77 articles were included for review. RESULTS AND CONCLUSION:(1)Tumor necrosis factor-α is participating in regulating the recruitment,appreciation,and differentiation of osteoprogenitor cells,but leads to osteoprogenitor cell stripping and death under specific environments.It also participates in bone resorption directly or indirectly through secreted enzymes.(2)Tumor necrosis factor-α can increase the level of inflammatory factors in the environment by activating relevant signaling pathways in osteoclast lineage cells or directly induce the generation of osteoclasts in specific environments.(3)Tumor necrosis factor-α can inhibit osteogenic differentiation by activating nuclear factor-κB signaling pathway,inhibiting the expression of transcription factors such as RUNX2 and Osterix,and inducing apoptosis and necrotizing apoptosis in osteoblasts.(4)Tumor necrosis factor-α inhibits osteogenesis and promotes osteoclastogenesis by activating the nuclear factor-κB signaling pathway in osteocytes and inducing cytokines such as RANKL,SOST,and DKK1,while enhancing apoptosis of the osteocytes,as well as bone resorption around the apoptotic bone tissue.(5)Taken together,the effect of tumor necrosis factor-α in bone tissue is mainly to inhibit osteogenesis and promote osteoclastosis.The biological effect of tumor necrosis factor-α in bone tissue cells is usually dependent on the activation of tumor necrosis factor receptor and nuclear factor-κB signaling pathways.(6)The interaction of tumor necrosis factor-α with other tissue cell types surrounding bone tissue and its role in bone immune regulation still deserve attention in future studies.
3.Effects of filament B knockdown on proliferation,migration and apoptosis of mouse MC3T3-E1 cells
Xi WANG ; Li YU ; Qiyu JIA ; Jinyong HUANG ; Zebiao LIU ; Jun ZHANG ; Dilimulati JIAYIDAER ; Zengru XIE ; Hairong MA
Chinese Journal of Tissue Engineering Research 2024;28(32):5177-5181
BACKGROUND:Filamin B(FLNB)can crosslink the actin cytoskeleton into a dynamic structure that is essential for the directional movement of cells.It can regulate the proliferation,differentiation and apoptosis of chondrocytes.However,the effect of FLNB on osteoblast proliferation,migration and apoptosis has not been reported. OBJECTIVE:To investigate the effect of FLNB on the proliferation,migration and apoptosis of MC3T3-E1 cells. METHODS:The adenoviral vectors for knockdown of FLNB expression(sh-FLNB1,sh-FLNB2,sh-FLNB3)were constructed and infected with MC3T3-E1 cells.After screened by puromycin drug,the efficiency of FLNB knockdown was detected by western blot and RT-PCR.The MC3T3-E1 cell line with the best efficiency of FLNB knockdown was selected as the stable transient cell line of MC3T3-E1 for subsequent experiments.The cells were divided into blank group,mc3t3 group,sh-NC group(empty vector),and sh-FLNB group(sh-FLNB lentivirus).The blank group was cultured in cell-free α-MEM complete medium;the mc3t3 group was cultured in α-MEM complete medium alone;and the sh-NC and sh-FLNB groups were cultured with α-MEM medium containing 2.5 μg/mL puromycin.After 3 days of culture,cell counting kit-8 assay and cell scratch assay were used to detect the proliferation and migration ability of MC3T3-E1;flow cytometry was used to detect cell apoptosis;and RT-PCR was used to detect the expression of apoptosis-related genes. RESULTS AND CONCLUSION:Western blot and RT-PCR results showed that the efficiency of FLNB knockdown was the best in the sh-FLNB3(P<0.000 1),which was used as a stable cell line for subsequent experiments.Cell counting kit-8 data showed that the proliferative ability of MC3T3 cells was significantly weakened after knockdown of FLNB(P<0.05).Cell scratch assay results showed that the migration ability of MC3T3 cells was significantly decreased after knockdown of FLNB.Flow cytometry and RT-PCR results showed that the apoptotic rate of MC3T3-E1 cells increased after knockdown of FLNB,the expression of pro-apoptotic factor Bax increased significantly,and the expression of anti-apoptotic factor Bcl-2 decreased significantly(P<0.05).To conclude,knockdown of FLNB can reduce the proliferation ability of MC3T3-E1 cells,decrease the migration ability of the cells,and increase cell apoptosis.
4.Research progress in microRNA as a novel diagnostic marker for bone echinococcosis
International Journal of Biomedical Engineering 2023;46(4):365-369
Bone echinococcosis is usually caused by Echinococcus granulosus and E. multilocularis. People become infected when they eat food or water contaminated with the eggs. Treatment of bone echinococcosis usually includes surgery and medication, but the lengthy and costly treatment imposes a heavy burden on patients. MicroRNAs (miRNA) are known to be involved in a variety of biological processes and host-host interactions, including development, cell growth and death, lifespan-related target regulation, transcription, signal transduction, and cell motility, which will help us find new strategies and targets for the treatment and control of osteonechoconiosis. For further understanding of bone echinococcosis, it is important to understand the molecular basis of E. multilocularis development in both final and intermediate hosts. The miRNA found in E. granulosus and E. multilocularis have gene and developmental stage specificity in their respective host expression regulation. In this review paper, the progress of research on miRNA as a novel diagnostic marker for osteoblastic echinococcosis is reviewed.
5.Analysis of risk factors for lower extremity deep venous thrombosis in patients with type C pelvic fracture patients after internal fixation and construction of related nomogram model
Xuefeng LUO ; Zhifei YI ; Zengru XIE
Chongqing Medicine 2023;52(23):3583-3588,3593
Objective To investigate the risk factors of lower extremity deep venous thrombosis(DVT)after internal fixation in patients with type C pelvic fracture,and to establish a relevent nomogram model.Methods Atotal of 217 patients with type C pelvic fractures who were admitted to the Orthopedic Center of the hospital from January 2018 to January 2022 were included in the study.All patients underwent internal fixation.According to whether DVT of the lower extremities was formed after operation,they were divided into the DVT group and the non-DVT group(N-DVT).The general clinical data and preoperative in-flammatory factor expression levels of the two groups was compared.Multivariate analysis was used to obtain independent predictors of DVT formation after internal fixation in patients with type C pelvic fractures.The correlation between preoperative inflammatory factors and DVT formation after internal fixation in patients with type C pelvic fractures was analyzed.The relevant nomograph model was constructed,and the Bootstrap method and calibration curve were used to verify the nomograph model internally.The ROC curve and deci-sion curve for predicting DVT formation after internal fixation in patients with type C pelvic fracture were drawn,and the predictive efficiency and net rate of return of independent prediction and combined prediction were an-alyzed.Results Multivariate analysis showed that age,diabetes,preoperative tumor necrosis factor-α(TNF-α),traction and braking,and bed rest time were independent predictors of DVT formation after internal fixa-tion in patients with type C pelvic fractures(P<0.05).A nomograph model was constructed based on inde-pendent predictors to predict the formation of DVT after internal fixation in patients with type C pelvic frac-ture,and the C index of the distinguishing evaluation index of the nomogram model was 0.834(95%CI:0.812-0.924),the results of goodness of fit(H-L)test showed that the predicted value of DVT formation probability after internal fixation in patients with type C pelvic fracture was in good agreement with the actual observed value(P>0.05).ROC curve analysis and decision curve analysis showed that age,diabetes,TNF-α,traction and braking,bed rest time and combined prediction model had good predictive performance and net yield in predicting DVT formation after internal fixation in patients with type C pelvic fracture.Conclusion Age,diabetes,TNF-α,traction braking and bed rest time are independent predictors of DVT formation after internal fixation in pa-tients with type C pelvic fracture.The nomogram model based on the above independent predictors has a high value in predicting DVT formation after internal fixation in patients with type C pelvic fracture.
6.Establishment of finite element model and biomechanical analysis of external fixation and combined external and internal fixation for bone transport in treatment of a case with bone defect of lower limb
Maimaiti XIAYIMAIERDAN ; Zengru XIE ; Kai LIU ; Hui CHEN ; Yusufu AIHEMAITIJIANG
Chinese Journal of Microsurgery 2023;46(4):436-441
Objective:To establish a finite element model for bone transport before surgery in the treatment of femoral and tibial bone defects with external fixation and combined intramedullary nails with external fixations, and evaluate the stability and properties of biomechanics.Methods:Between May 2022 and August 2022, a male volunteer in the Department of Trauma and Microreconstructive Surgery, the First Affiliated Hospital of Xinjiang Medical University was selected. The right lower limb was scanned using 64-slice CT. Data were imported into Mimics 21.0 to establish normal geometric models of femur and tibia. The models were arranged in 4 groups: a femoral external fixator group, a femoral external fixator combined with intramedullary nail group, a tibial external fixator group and a tibial external fixator combined with intramedullary nail group. Hypermesh 10.0 was used for meshing. Finite element analysis was performed by Ansys v.11 to measure the distribution and characteristics of equivalent stress in the transported bone segment, proximal and distal tibia, and fixtures in the 2 treatment modalities, respectively.Results:Peak Von Mises equivalent stress of cortical bone and external fixation was found higher in both of the femoral and tibial external fixator combined with intramedullary nail groups than that in the external fixator group, with stress reduction on cortical bone at approximately 76.9% and 77.8%, respectively. The stress reduction on external fixator was about 81.4% and 76.3%, respectively. Peak displacement of the structure in both of the femoral and tibial external fixator combined with intramedullary nail groups was lower than that in the external fixator group, with 78.4% and 60.1% reduction in displacement, respectively.Conclusion:Bone transport with intramedullary nailing combined with external fixator in treatment of femoral and tibial defects would offer better biomechanical advantages. It can facilitates bone regeneration and bone mineralisation during distraction phase and consolidation phase.
7.A finite element analysis of two internal fixation methods for unstable femoral neck fractures in young adults
Tuxun AIKEBAIER· ; Keremu AJIMU· ; Zengru XIE ; Wen ZHANG
Chinese Journal of Orthopaedic Trauma 2020;22(9):793-798
Objective:To compare internal fixation with 3 cannulated screws versus with an anteromedial support plate plus 3 cannulated screws using finite element analysis for unstable femoral neck fractures (Pauwels type Ⅲ).Methods:Recruited for this study was a 34-year-old male volunteer with a height of 173 cm and a weight of 75 kg. Continuous thin-layer helical CT was conducted to scan the segment from his hip joint to the middle shaft of his tibia. Digital medical software was used to establish three-dimensional models of the femur based on his femoral CT data. The digital femoral necks were dissected as necessary to simulate femoral neck fractures of Pauwels type Ⅲ. The fractures were fixated with 3 ordinary cannulated screws in a mode of inverted triangle (screw group) and with 3 ordinary cannulated screws in a mode of inverted triangle plus an anteromedial steel plate (screw-plate group). After the 2 groups of models were subjected to identical constraints and 3 kinds of load (slow walking, twisting and standing on one leg), they were compared in terms of distribution of Von Mises stress and deformation.Results:Under various loads in both groups, the maximum deformation occurred in the femoral head. In the condition of slow walking, the deformation in the screw-plate group was 1.97 mm, which was smaller than that in the screw group (2.26 mm). In the conditions of twisting and standing on one leg, similar deformations were observed in both groups. Under all kinds of load, the maximum stress occurred in the middle part of the bottom screw and the fracture line in all the models. In the screw group, the peak stresses were 318.09 MPa, 92.11 MPa and 147.21 MPa for conditions of slow walking, twisting and standing on one leg, greater than those in the screw-plate group (229.86 MPa, 86.94 MPa and 124.48 MPa).Conclusions:The cannulated screws plus an anteromedial support plate are a recommendable fixation method for young adults with unstable femoral neck fracture, because they can effectively share the stress on the cannulated screws, lead to better mechanical stability of the fracture ends than the fixation with merely 3 cannulated screws and effectively prevent shortening of the femoral neck.
8.Treatment of femoral intertrochanteric fractures by reduction without a traction table in a special position and fixation with proximal femoral nail antirotation (PFNA)
Jinlong MA ; Mahan WULUHAN· ; Xuefeng LUO ; Yahui TANG ; Zhongzheng WANG ; Zengru XIE
Chinese Journal of Orthopaedic Trauma 2018;20(3):258-262
Objective To study the treatment of femoral intertrochanteric fractures by reduction without a traction table in a special position and fixation with proximal femoral nail antirotation (PFNA).Methods From May 2016 to May 2017,34 patients with femoral intertrochanteric fracture were treated with PFNA.They were 20 men and 14 women,from 36 to 89 years of age (average,69.9 years).The left side was affected in 15 cases and the right side in 19.By AO classification,there were 10 cases of type AO 31-A1,13 ones of type 31-A2,and 11 ones of type 3 l-A3.Two cases were complicated with other fractures,and 5 with internal system disease,3 of whom had more than 2 concomitant diseases.Preoperative deep venous thrombosis was found in 2 cases.Surgery was performed for them between 2 and 8 days after injury (average,3.7 days).Reduction was performed in a special position without a traction table.The duration of anesthesia,operation time,intraoperative hemorrhage,postoperative complications and hip function by Harris scores were recorded.Results For the 34 patients,the anesthesia time ranged from 57 to 85 min (average,67.5 min),the operation time ranged from 28 to 65 min (average,40.9 min),and the intraoperative hemorrhage from 80 to 150 mL (average,110.6 mL).They received effective follow-up for 6 to 12 months (average,8.4 months).All the fractures healed after 6 to 12 months(average,7.2 months).No failure of internal fixation was observed during follow-ups.By the Harris scores at the final follow-up,the function of the affected hip was rated as excellent in 9 cases,as good in 21 and as fair in 4,giving an excellent to good rate of 88.2%.Conclusion In the treatment of femoral intertrochanteric fractures,reduction without a traction table in a special position and PFNA fixation may reduce anesthesia time,leading to satisfactory clinical outcomes.
9.A preliminary study on the outcomes of radiation therapy of bone hydatid disease in Meriones meridianus
Jun WU ; Liang CHEN ; Xuefeng LUO ; Shiyuan YIN ; Yahui TANG ; Zengru XIE
Chinese Journal of Endemiology 2015;34(11):800-804
Objective According to radiation therapy (6WV-X line) on experimental gerbils which were successfully infected by echinococcus granulosus,the outcomes of bone hydatid disease after radiation therapy were studied.Methods Totally 240 gerbil models that were infected bone hydatid disease,were randomly divided into three groups (each group was further divided into three-month and six-month groups,40 gerbils per group),one group as a control group,the 40 Gy/5 times and 50 Gy/5 times groups were given 6WV-X line radiation therapy.After 5 consecutive radiation therapies,stopped for two days and then repeated for five times.At the end of three and six months after radiotherapy,the rate of death and the ulceration or infection of the lesions was compared.Fifteen gerbils from each group were randomly selected to observe the deaths of scolex,protein and calcium concentration changes,the maximum diameter changes of the lesions,the changes of hydatid cyst wet weight and the rate of suppressing capsule,the bone destruction,and rebuilding situation of lesions under a microscope.Results At the end of three and six months after radiation therapy,with increasing dosage,the deaths decreased significantly (x2 =10.4,17.4,all P < 0.05);the ulceration or infection of the lesions decreased significantly (x2 =6.0,10.1,all P < 0.05);the mortality rate of scolex increased [3 month:(22.4 ± 3.1),(95.0 ± 5.2),(136.0 ± 5.4);6 month:(23.2 ± 2.2),(98.2 ± 4.6),(169.3 ± 7.0);F =2 252.5,3 220.3,all P < 0.05];the concentration of protein and the calcium ion were changed significantly [3 month:(1.059 ± 0.056),(0.733 ± 0.051),(0.571 ± 0.043)g/L and (2.802 ± 0.157),(3.056 ± 0.060),(3.546 ± 0.135)mmol/L;6 month:(1.088 ± 0.043),(0.753 ± 0.034),(0.340 ± 0.032)g/L and (2.804 ± 0.019),(3.068 ± 0.052),(3.886 ± 0.046)mmol/L;F =366.0,138.9 and 1 550.5,2 727.3,all P < 0.05];the maximum diameters of the lesions reduced significantly [3 month:(2.38 ± 0.14),(1.69 ± 0.05),(1.40 ± 0.09)cm;6 month:(2.65 ± 0.05),(1.69 ± 0.03),(1.03 ± 0.06)cm;F =372.5,3 846.1,all P < 0.05];the hydatid cyst wet weight decreased significantly [3 month:(3.47 ± 0.11),(2.54 ± 0.12),(1.46 ± 0.07)g;6 month:(3.75 ± 0.31),(2.55 ± 0.08),(1.02 ± 0.20)g;F =1 475.6,608.0,all P < 0.05].In the same group with time went on,in the control and 40 Gy/5 times group,the deaths gradually increased (x2 =4.3,4.6,all P < 0.05),but in the 50 Gy/5 times group,the deaths was not significantly increased (x2 =1.1,P > 0.05);in the control and 40 Gy/5 times group,the ulceration or infection of the lesions gradually increased (x2 =5.5,4.3,all P < 0.05),but in the 50 Gy/5 times group,the ulceration or infection of the lesions did not change significantly (x2 =0.3,P > 0.05);in the 50 Gy/5 times group,the mortality rate of scolex was significantly increased (F =212.6,P < 0.05);in 50 Gy/5 times group,the protein (calcium) concentration decreased (increased) significantly (F =271.8,84.7,all P < 0.05);the maximum diameters of the lesions increased gradually in the control group (F =47.1,P < 0.05),in 50 Gy/5 times group,the maximum diameters of the lesions decreased gradually (F =188.3,P < 0.05);in the control group,hydatid cyst wet weight increased significantly (F =10.7,P < 0.05),in the 50 Gy/5 times group,hydatid cyst wet weight was significantly reduced (F =68.5,P < 0.05);with increasing dosage,the damage of the bone matrix and the cells in lacunae of the lesions gradually increased,in the same group with time went on,in the control group,a few amount of bone cells in lacuna died,and in 40 Gy/5 times and 50 Gy/5 times groups,the bone matrix and bone cells were partially repaired.Conclusion The long-term effects of appropriate dosage (50 Gy/5 times) radiation on experiments hydatid diseased gerbils are affirmed,but it is still need a clinical validation.
10.The potential role of original fracture hematoma in fracture healing
Liang LIN ; Yahui TANG ; Luhan WU ; Zengru XIE
Chinese Journal of Tissue Engineering Research 2015;(46):7386-7390
BACKGROUND:In closed fractures, the initial hematoma that is inclined to remove is seldom considered as the important reasons for bone healing. OBJECTIVE:To observe the mechanism and potential role of original fracture hematoma in fracture healing. METHODS:Ninety-six patients with closed fractures of the long bones undergoing open reduction and internal fixation were randomly divided into experimental group (n=48) and control group (n=48). In the experimental group, original fracture hematoma, 1.0-2.0 mL, was first taken out during the internal fixation and placed into a special sterile plastic bag; then, 3-4 pieces of hematomas were filed into the fracture site and sutured layer by layer. On the contrary, original fracture hematomas from the control group were discarded. Blood samples were extracted to detect the biochemical indicators at 1 month after internal fixation. X-ray examination was done at 1, 3, 6 months after internal fixation for observation of fracture healing. RESULTS AND CONCLUSION: X-ray films showed that the healing rate at 3 months after operation was 95% in the experimental group and 78% in the control group, and there was a significant difference between the two groups (P < 0.05). Levels of bone glaprotein, I-type precolagen carboxy terminus peptide and serum bone alkaline phosphatase were significantly higher in the experimental group than the control group (P < 0.01 orP < 0.05). These findings indicate that the original fracture hematoma can accelerate calus formation, promote bone induction, provide nutrition to the fracture site, and participate in revascularization. Therefore, the original fracture hematomas is one of the effectively therapeutic methods for union and nonunion of fractures.

Result Analysis
Print
Save
E-mail