Biological Mechanism And Clinical Practice Of Recurrent Patellar Instability With Trochlear Dysplasia

Part One Biological mechanisms of trochlear dysplasia regulated by mechanical stressObjective: To detect the differentially expressed genes in the development of trochlear dysplasia,screen out the potential key hub genes and molecular biological mechanisms in the development of trochlear dysplasia after abnormal stress,and explore the regulatory effect of key hub genes on angiogenesis in bone tissue,in order to clarify the biological mechanism of mechanical stress regulating trochlear dysplasia.Methods: 1.In this study,RNA sequencing was used to explore the differences in gene expression in the development of trochlear dysplasia,bioinformatics analysis was used to determine the signaling pathways affecting trochlear dysplasia,and protein interaction network was used to screen the potential key hub genes and molecular mechanisms in the development of trochlear dysplasia after abnormal stress;2.Western blot,immunofluorescent staining,flow cytometry and micro-CT were used to explore the upstream pathway of mechanical stress regulating the coupling of angiogenesis and osteogenesis in vivo,and to find the mechanism of mechanical stress regulating the coupling of angiogenesis and osteogenesis.Results: 1.A total of 101 differentially expressed genes were identified in trochlear dysplasia,31 genes up-regulated and 70 genes down-regulated.GO enrichment analysis indicated that the differentially expressed genes in trochlear dysplasia were closely related to protein translation,lipid metabolism,redox reaction,phagocytosis,apoptosis,proteolysis,signal transduction,and fatty acid biosynthesis.KEEG enrichment analysis showed that ribosome function,PPAR signaling pathway,AMPK signaling pathway,and apoptosis were important pathways involved in trochlear dysplasia.Rps10,Cpt1 a and Ctsl were key genes involved in ribosome function,PPAR signaling pathway and apoptosis,respectively;2.We subsequently found that Cpt1 a expression was down-regulated through PPAR signaling in chondrocytes under stress unload,and further verified that down-regulation of Cpt1 a could reduce VEGF production,reduce type H endothelial cell production,affect the coupling process of angiogenesis and osteogenesis,and ultimately lead to the reduction of subchondral bone osteogenesis and trochlea dysplasia.Conclusions: The biological mechanism of mechanical stress regulating femoral trochlea dysplasia may be that after mechanical stress unloading,the development and metabolism of chondrocytes are abnormal,and the expression of VEGF is down-regulated through the inhibition of Cpt1 a expression through the PPAR signaling pathway,which inhibits the coupling process of angiogenesis and osteogenesis in bone tissue,and eventually leads to the reduction of bone formation and remodeling.And then lead to the occurrence of trochlear dysplasia.It provides new insights into the mechanism of trochlear dysplasia and potential targets for intervention.Part Two Analysis of the causes of femoral anteversion increase in recurrent patellar instability with trochlear dysplasiaObjective: Femoral anteversion is defined by the femoral neck axis and the posterior femoral condyle line.Increased femoral anteversion is reportedly associated with patellar dislocation and trochlear dysplasia,but it is unclear whether the increase is due to abnormal development of the femoral condyle,and the increase of femoral anteversion may occur at different segments of the femur.This study was aimed to explore the difference in femoral anteversion and the torsion distribution among different femoral sections between a control group,a group with patellar instability and trochlear dysplasia,and a group with patellar instability but without trochlear dysplasia,and to investigate the association between femoral anteversion and femoral condyle morphology.Methods: This study involved 132 knees: 44 control knees,44 knees with patellar instability and trochlear dysplasia,and 44 knees with patellar instability but without trochlear dysplasia.The femoral anteversion,proximal torsion,middle torsion,distal torsion,and distal femoral condyle morphology were measured.Differences were investigated by one-way analysis of variance.Pearson’s correlation was conducted to explore the association between femoral anteversion and each parameter.Results: Femoral anteversion was significantly larger in the trochlear dysplasia group(25.4°±4.7°)than in the other groups(18.9°±5.6°,19.9°±4.8°).Distal torsion was significantly larger in the trochlear dysplasia group(15.8°±2.9°)than in the other groups(9.0°±4.3°,8.8°±3.9°).Femoral anteversion was strongly correlated with distal torsion in all three groups(r=0.76,0.80,and 0.88,respectively).Femoral anteversion had a strong positive correlation with the posteromedial condyle length(r=0.48,0.48,and 0.70,respectively)and a strong negative correlation with the posterolateral condyle length(r=-0.30,-0.35,and-0.78,respectively)in the three groups.Conclusions: The femoral anteversion is increased in trochlear dysplasia knees,associated with associated with dysplasia of the posterior condyle of the femur,the increase is mainly due to distal torsion rather than proximal or middle torsion,which may provide a reference for choosing the optimal position for femoral derotation osteotomy.Patients with trochlear dysplasia are prone to develop recurrent patellar instability,which may be due to malalignment of the patellofemoral joint caused by abnormal rotation.Part Three Predictive efficacy of femoral anteversion and axial orientation of the trochlea for recurrent patellar instabilityObjective: The femoral anteversion is considered to be the same as femoral torsion,however,the femoral anteversion is strongly influenced by the femoral posterior condylar morphology.It remains unclear whether the femoral anteversion and axial orientation of the femoral trochlea can predict patellar instability.This study aimed to redefine the femoral inherent torsion,verify whether the femoral anteversion reflects the femoral inherent torsion,and compare the validity and calculate the cutoff values of the femoral anteversion and femoral trochlear axial orientation for predicting patellar instability.Methods: Seventy-three patients with patellar instability and 73 matched controls underwent computed tomography to measure the femoral anteversion,femoral inherent torsion,and femoral trochlear axial orientation.Pearson’s product moment correlation coefficients and linear regression were calculated to determine correlations between measurements.Receiver operating characteristic curves and nomograms were plotted to evaluate the predictive validity of the femoral anteversion angle and femoral trochlear axial orientation for patellar instability.Results: All measurements showed excellent intra-and inter-observer reliability.Compared with the control group,the patellar instability group had a significantly larger femoral anteversion(25.4°±6.4° vs 20.2°±4.5°)and femoral inherent torsion(18.3°±6.7° vs 15.8°±3.4°),and significantly smaller femoral trochlear axial orientation(58.1°±7.3° vs 66.9°±5.1°).The femoral anteversion and femoral trochlear axial orientation had area under the receiver operating characteristic curve values of 79% and 84%,respectively,and cutoff values of 24.5° and 62.7°,respectively.The calibration curve and decision curve analysis showed that the femoral trochlear axial orientation performed better than the femoral anteversion in predicting patellar instability.There was a strong correlation between the femoral anteversion and femoral inherent torsion(r>0.8).Linear regression analysis of the femoral inherent torsion with the femoral anteversion as the prediction variate showed moderate goodness-of-fit(adjusted R2=0.69).Conclusions: The femoral anteversion moderately reflects the femoral inherent torsion.The femoral trochlear axial orientation is better than the femoral anteversion in predicting patellar instability in terms of predictive efficiency,consistency with reality,and net clinical benefit.These findings warn orthopaedists against overstating the role of the femoral anteversion in patellar instability,and suggest that the femoral trochlear axial orientation could aid in identifying at-risk patients and provide a new reference index for osteotomy surgery for recurrent patellar instability.Part Four Trochleoplasty combined with individualized procedures for recurrent patellar instability with trochlear dysplasiaObjective: The current researches of treating recurrent patellar instability with severe trochlear dysplasia were mainly concentrated on trochleoplasty combined with medial patellofemoral ligament reconstruction,while patients with trochlear dysplasia are often complicated by other pathological factors of patellar instability,studies on individual extensor apparatus balancing combined with trochleoplasty were rarely reported.Our study is aimed to verify the safety and efficacy of sulcus deepening trochleoplasty combined with individualized extensor apparatus balancing for recurrent patellar instability with severe trochlear dysplasia.Methods: Twenty-five patients(mean age,25±6.7 years)of recurrent patellar instability with severe trochlear dysplasia(Dejour B and D),treated by sulcus deepening trochleoplasty combined with some of the following procedures: medial patellofemoral ligament reconstruction,medial patellar retinacular reefing,lateral patellar retinaculum plasty,medial tibial tubercle osteotomy,and distal tibial tubercle osteotomy.Preoperative and postoperative Banff patellofemoral instability instrument(BPII),International Knee Documentation Committee score(IKDC),Tegner activity scale(TAS),and Marx activity rating scale(MARS)were recorded.visual analog scale(VAS)for pain severity,self-reported satisfaction score(SSS),and the athletic ability were assessed.The Sulcus angle(SA),patellar tilt angle(PTA),lateral patellar translation(LPT),and Caton-Deschamps index(CDI)were also measured.Results: At the end of the follow-up of mean 54.5±7.4 months,the BPII increased from 37.1±7.1 to 79.5±5.8,IKDC from 58.8±8.5 to 90.1±5.7,TAS from 3.7±0.8 to 6.1±1.1,MARS from 5.2±1.1 to 12.0±1.4,SSS increased from4.3±0.7 to 8.4±0.9,and the VAS decreased from 5.6±1.2 to 2.2±0.7,significantly.The SA decreases from 171.1°±8.1° to 136.8°±6.5°,PTA from32.9°±3.3° to 7.9°±3.0°,LPT from 2.9±0.3 to 0.5±0.1 cm,and CDI from1.14±0.06 to 1.10±0.04,significantly.The athletic ability was improved.All patients obtained full range-of-motion,no re-dislocations,arthrofibrosis or progressive patellofemoral osteoarthritis was found.Conclusions: The sulcus deepening trochleoplasty combined with individualized extensor apparatus balancing procedures is safe and effective for recurrent patellar instability with severe trochlear dysplasia,which could achieve patellar stability,restore more normal morphology of trochlear,reduce the lateral patellar tilt,helping prevent patella from re-dislocations or abnormal tracking and achieve good function and athletic ability.According to the specific pathological factors of the patient,choosing the corresponding combined procedures can achieve satisfactory effect.