ABSTRACT
Objective To detect the osteopontin (OPN) autocrine function of the osteoclasts in neurofibromatosis type 1 heterozygote (Nfl+/-) and wild type (Nfl+/+) mice.Test the osteoclasts function of neurofibromatosis type 1 heterozygote (Nfl+/-) and wild type (Nil+/+) mice with exogenous neutralizing OPN antibody,analysis the role of autocrine OPN in the hyperfunction of osteoclast in neurofibromatosis type 1.Methods Culture the low density bone marrow cells from Nfl heterozygote (Nfl+/-) and wild type (Nfl+/+) mice (4-6 weeks old) with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand(RANKL),Measure.the OPN concentration in osteoclast culture superenant with ELISA.Culture the low density bone marrow cells from Nf1+/-and Nf1+/+ mice with or without exogenous neutralizing antibody for OPN.The function of osteoclasts and osteoclast progenitors in formation,migration,adhesion,and bone absorption were tested.Results A significantly higher concentration of OPN was detected in the Nf1+/-osteoclast culture media as compared to that of wild type.In control,Osteoclast functions,including migration,adhesion,and bone resorption of Nf1 +/-were higher than that of wild type.Addition OPN neutralizing antibody to the Nf1+/-OCL significantly reduced OCL formation.Neutralizing OPN antibody diminished both wild type and Nf1+/-OCL adhensiontion,Anti-OPN minimized OCL migration in both wild type and Nf1 +/-OCL cultures as measured by the transwell assays.Neutralizing OPN antibody diminished both wild type and Nf1+/-OCL pit formation,P＞0.05 for comparing Nfl+/-vs.wild type OCLs with anti-OPN antibody.Conclusion The hyperfunction of osteoclast in Nf1 heterozygote is related with autocrine osteopontin,inhibition of OPN may be an effective treatment for bone destruction of neurofibromatosis type 1.
ABSTRACT
BACKGROUND:Finite element analysis has been widely used for the research of bone and joint biomechanics, but the reports about finite element analysis of distal tibial articular surface defect are rare at home and abroad. OBJECTIVE:To establish ankle three-dimensional finite element model, produce distal tibial articular surface defects with different areas, and to simulate the distal tibial articular surface deformation and displacement under the different phases, thus predict the maximum al owable degree of distal tibial articular surface defect and explore the mechanics pathogenesis of ankle traumatic arthritis. METHODS:Continuous tomographic images were obtained by multi-slice spiral CT scan of a normal adult male ankle, and then the images were imported into the Mimics medicine modeling software to generate a entity model;the large general-purpose finite element analysis software ANSYS 13.0 was used for meshing, material property assignment and generating a finite element model. Restricted boundary conditions and simulated ankle distal end axial force, and then the stress distribution and displacement results of distal tibial articular surface in different phases were obtained. RESULTS AND CONCLUSION:The total number of units of the established finite element model of ankle joint was 157 990, and the total number of nodes was 193 801. On three phases, with the increase of the distal tibial defect area, the contact area was gradual y decreased, especial y in plantar flexion with the defect diameter of 13 mm, the change of the area was most obvious;The contact area of the neutral position was largest;with the increase of the distal tibial defect area in the neutral position and dorsiflexion, the peak stress was increased gradual y, and significantly increased after the diameter changed into 11-13 mm;in the neutral position and 10° of dorsiflexion, the peak stress mainly concentrated in the posteromedial and posterolateral quadrant;in 10° of plantar flexion, the change was complex, and when the diameter was 11-13 mm, the peak stress was increased gradual y with the increasing of defect area, when the diameter increased to 13 mm, the peak stress reached maximum. The maximum diameter of distal tibial articular surface defect was considered to be 11-13 mm. The joint function wil be affected when the diameter of distal tibial articular cartilage and bone bed defects was more than 11-13 mm.