Mechanical alignment (MA) in total knee arthroplasty (TKA), although considered the gold standard, reportedly has up to 25% of patients expressing post-operative dissatisfaction. Biomechanical outcomes following kinematic alignment (KA) in TKA, developed to restore native joint alignment, remain unclear. Without a clear consensus for the optimal alignment strategy during TKA, the purpose of this study was to conduct a paired biomechanical comparison of MA and KA in TKA by experimentally quantifying joint laxity and medial collateral ligament (MCL) strain. 14 bilateral native fresh-frozen cadaveric lower limbs underwent medially-stabilised TKA (GMK Sphere, Medacta, Switzerland) using computed CT-based subject-specific guides, with KA and MA performed on left and right legs, respectively. Each specimen was subjected to sensor-controlled mediolateral laxity tests. A handheld force sensor (Mark-10, USA) was used to generate an abduction-adduction moment of 10Nm at the knee at fixed flexion angles (0°, 30°, 60°, 90°). A digital image correlation system was used to compute the strain on the superficial medial collateral ligament. A six-camera optical motion capture system (Vicon MX+, UK) was used to acquire kinematics using a pre-defined CT-based anatomical coordinate system. A linear mixed model and Tukey's posthoc test were performed to compare native, KA and MA conditions (p<0.05). Unlike MA, medial joint laxity in KA was similar to the native condition; however, no significant difference was found at any flexion angle (p>0.08). Likewise, KA was comparable with the native condition for lateral joint laxity, except at 30°, and no statistical difference was observed. Although joint laxity in MA seemed lower than the native condition, this difference was significant only for 30° flexion (p=0.01). Both KA and MA exhibited smaller MCL strain at 0° and 30°; however, all conditions were similar at 60° and 90°. Medial and lateral joint laxity seemed to have been restored better following KA than MA; however, KA did not outperform MA in MCL strain, especially after mid-flexion. Although this study provides only preliminary indications regarding the optimal alignment strategy to restore native kinematics following TKA, further research in postoperative joint biomechanics for load bearing conditions is warranted.
LY3023414 is a novel oral phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor designed for advanced cancers, for which a phase II clinical study was completed in March 2020; however, little is known about its effect on bone modelling/remodelling. In this study, we aimed to explore the function of LY3023414 in bone modelling/remodelling. The function of LY3023414 was explored in the context of osteogenesis (bone formation by osteoblasts) and osteoclastogenesis (osteoclast formation and bone resorption). Murine preosteoblast MC3T3-E1 cell line and murine bone marrow-derived macrophage cells (BMMs) were subjected to different treatments. An MTS cell proliferation assay was used to examine the cytotoxicity. Thereafter, different induction conditions were applied, such as MCSF and RANKL for osteoclastogenesis and osteogenic media for osteogenesis. Specific staining, a bone resorption assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were subsequently used to evaluate the effect of LY3023414. Moreover, small interfering RNA (siRNA) was applied to knockdown Akt1 or Akt2 for further validation. Lastly, western blot was used to examine the exact mechanism of action.Aims
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