Expression Of Sclerostin And ?-catenin In Bone Tissue Of Patients With Osteoporotic Fracture

Background: Osteoporosis(OP)is characterized by reduced bone mass and microstructure of the bone,accompanied by increased brittleness of the bone and systemic skeletal disease that is prone to fracture.Accompanied by medical development,for the OP has a clear understanding and a lot of research,China also OP as a national focus on the capture of one of the three major diseases.The most serious consequence of OP is osteoporotic fracture(OPF).Compared with the general fracture that is not OPF,OPF healing time is slow,fracture fixation is easy to lose,the reliability of internal fixation is reduced,the probability of recurrence of fracture is higher.Therefore,how to effectively solve OP and OPF is a daunting task in front of clinicians.The process of OPF healing is complex and continuous,including histological,biomechanical and endocrine changes,including osteoblasts(OB),osteoclasts(OC),bone marrow stromal Cells,BMSCs),various inflammatory cells and other cells involved in the role of coordination and behavior.Therefore,OPF fracture not only to the fracture treatment,but also for anti-osteoporosis treatment.Many studies have shown that the proliferation of BMSCs and the differentiation of OBs in elderly patients with OPF may indicate that BMSCs are one of the main causes of fracture healing.Wnt signal path is more complex and huge,involving a lot of factors,the mechanism of regulation has been complicated,but also with other signal systems and a variety of cytokines interact.Wnt / ?-catenin pathway plays an important role in the proliferation of BMSCs and OB differentiation.Beta-catenin(?-catenin)is one of the key factors of Wnt / ?-catenin pathway,which can influence the target gene of OB differentiation from transcription.Knockout mouse ?-catenin gene,the OB differentiation stagnation in the early progenitor cell stage.Therefore,?-catenin significantly promoted the role of OB differentiation.The bone sclerotic protein(Sclerostin,SO)derived from bone cells is a negative regulator of bone formation,mainly because of inhibition of classical Wnt / ?-catenin signaling pathway,and thus inhibition of bone differentiation and bone formation.Knockout of mouse SO genes promotes bone formation and increases bone strength.Studies have shown that knockout of mouse SO gene to accelerate fracture healing is mainly due to the activation of ?-catenin.Gene and above research,this topic is mainly from sclerostin and ?-catenin to study the sclerostin / ?-catenin and OPF association.At present,this research is mainly based on in vitro experiments,such as the cultivation of animal models and off-topic cell culture,as well as some people's serum research,but rarely in human tissue as the object of study.However,regardless of the kind of in vitro research methods can not true response to human bone tissue gene expression level,so this study to remove the bone tissue surgery for the study,can more really reflect the OPF patients in the process of fracture healing Sclerostin and ?-catenin levels.To more in-depth understanding and study of the pathophysiology of OPF.Objective: The aim of this study was to compare the expression of Sclerostin and ?-catenin in OPF patients and non-OPF patients by protein expression and immunohistochemistry in patients with OPF at different time and non-OPF patients with fractured bone.To investigate the clinical significance of Wnt / ?-catenin pathway and OPF,and to provide theoretical basis for the study and treatment of OPF.Methods: Choose from September 2016-April 2017 in our hospital and meet the conditions of 38 patients.All subjects were examined by dual energy X-ray absorptiometry,and the relevant information such as sex,age and height were registered,and then divided into two groups according to WHO diagnostic criteria: OPF group and non OPF group General fracture group),OPF group according to the fracture to the time between the operation of the different sub-group.The bone tissue samples were fixed on the other hand,and the specimens were fixed with paraffin embedding.The IHC-P experiments were performed on the bone tissue samples.The levels of Sclerostin and ?-catenin,the key proteins of the classical Wnt / ?-catenin signaling pathway,were compared between the OPF and the non-OPF group and the patients in the OPF at different time intervals after WBC and IHC-P.In the expression of Sclerostin and ?-catenin,the data of WB experimental data were expressed as mean ± standard deviation(x ± s).Statistical analysis was performed using Image J image analysis,SPSS19.0,Graph pad Prisma 5 software related statistical chartResults: OPF group patients were common in hip fractures,fractures to the majority of women,because this experiment OPF group of non-vertebral bone tissue,it cannot be counted vertebral body of OPF patients,non-OPF group of patients with limb fractures,Significant differences.In the WB test,the protein expression in the same group was significantly lower than that in the untreated group.The results of the two groups did not affect the final outcome of the experiment.Therefore,the bone was subjected to WB Bones in the experiment without additional cleaning,can be used directly for the WB experiment.WB experiment,compared with the OPF group of distal femoral neck fracture and proximal bone tissue experiments found that there was no significant difference between the two groups of protein expression,for 4 weeks within the OPF group of femoral neck fractures in patients with bone tissue WB experiment,no distinction Distal and proximal femoral neck.The expression of Sclerostin protein in OPF patients was higher than that in patients with OPF.The Sclerostin protein in OP patients was also higher than that in patients with OPF.-catenin pathway,inhibition of bone formation,may accelerate the occurrence of OP,while its high expression delay OPF healing,OPF healing may be related to this slow.?-catenin was expressed in the bone tissue of OPF group at the early stage(0-2 weeks),and the expression of ?-catenin was increased(P <0.05),which may be related to the Wnt / ?-catenin signaling pathway,But this is not enough for bone formation and bone deposition to return to a dynamic balance,since Sclerostin is more potent for the Wnt / beta-catenin signaling pathway,so OP and OPF require intervention.Conclusions: 1.Bone on the bone tissue for WB experiments,remove the bones without additional cleaning,can be directly used for WB experiments.2.There was no significant change in Sclerostin and ?-catenin protein expression in the distal and proximal bone tissues of the femoral neck fracture(within 3-4 weeks).3.The expression of Sclerostin protein in bone tissue of patients with OPF fractures was significantly increased and increased in a certain period to inhibit Wnt / ?-catenin pathway.It was presumed that the occurrence of OP was related to its high expression.4.The expression of ?-catenin in the non-OPF group was higher than that in the OPF group(0-2 weeks).The expression of ?-catenin was gradually increased after a period(3-4 weeks).5.The sustained high expression of Sclerostin in OPF patients inhibited the Wnt / ?-catenin pathway,inhibited bone formation,accelerated the occurrence of OP and delayed the healing of OPF,and the high expression of ?-catenin for a period of time(3-4 weeks)Cannot restore the bone marrow and bone deposition of the dynamic balance,OP and OPF need intervention.