A kinematically aligned TKA results in a joint line which has a more parallel orientation in relation to the floor during single- and double-leg standing, and more neutral weight-bearing in tMA than a mechanically aligned TKA. Cite this article: 2017;99-B:640-6.

Objective Emerging evidence suggests that genetic components contribute significantly to cartilage degeneration in osteoarthritis pathophysiology but little evidence is available on genetics of cartilage regeneration. Therefore, we investigated cartilage regeneration in genetic murine models using common inbred strains and a set of recombinant inbred lines generated from LG/J (healer of ear-wounds) and SM/J (non-healer) inbred strains. Methods An acute full-thickness cartilage injury was introduced through microsurgery in the trochlear groove of 8-weeks old mice (N=265). Knee joints were sagittally sectioned and stained with toluidine blue to evaluate regeneration. For ear-wound phenotype, a bilateral 2-mm through-and-through puncture was made (N=229) at 6-weeks and healing outcomes measured after 30-days. Broad-sense heritability and genetic correlations were calculated for both phenotypes. Results Time-course studies from recombinant inbred lines show no significant regeneration until 16-weeks post-surgery; at that time, the strains can be segregated into three categories: good, intermediate and poor healers. Heritability (H2) showed that both cartilage regeneration (H2=26%; p=0.006) and ear-wound closure (H2=53%; p<0.00001) are significantly heritable. The genetic correlations between the two healing phenotypes for common inbred strains (r=0.92) and recombinant inbred lines (r=0.86) were found to be extremely high. Conclusion We report that i) articular cartilage regeneration is heritable, ii) the differences between the lines being due to genetic differences and iii) a strong genetic correlation between the two phenotypes exists indicating that they plausibly share a common genetic basis. We, therefore, surmise that LG/J by SM/J intercross can be used to dissect the genetic basis of variation in cartilage regeneration.

C-reactive protein is an excellent marker for plaque instability or poststent inflammatory status, and its source might be the inflammation site of the plaque or the coronary arterial wall injured by stenting.

La autoantigen is a 47-kDa nuclear protein that binds to nascent polymerase III transcripts and a number of viral RNAs. We show that La protein was cleaved to generate a 43-kDa fragment during apoptosis of human leukemic HL-60 cells treated with camptothecin or etoposide. Immunofluorescence microscopy showed that the La protein level was increased in the cytoplasm during apoptosis of HL-60 cells. In addition, UV irradiation of HeLa cells led to the cleavage and redistribution of La protein upon apoptosis. Several lines of evidence show that La protein is cleaved by caspase-3 or closely related proteases at Asp-374 in the COOH terminus. When the full-length (La) and COOH-terminally truncated (La⌬C374) forms of La protein were expressed as fusion proteins with green fluorescence protein (GFP), GFP-La⌬C374 was predominantly cytoplasmic, whereas GFP-La was localized in the nucleus. These results suggest that La protein loses the nuclear localization signal residing in the COOH terminus upon cleavage and is thus redistributed to the cytoplasm during apoptosis.Apoptosis is accompanied by disorganization of the nuclear architecture, cytoskeleton, and cell membrane. Proteolytic cleavage of key substrates is an important biochemical mechanism underlying the apoptotic process, and interleukin-1␤-converting enzyme-like proteases have been reported to play crucial roles as mediators of apoptosis (1-3). Identifying substrates of interleukin-1␤-converting enzyme or interleukin-1␤-converting enzyme-like proteases and determining cleavage sites are important to understand the apoptotic process.A variety of antitumor drugs have been shown to induce apoptosis and to cause changes in nuclear morphology in rapidly proliferating cells, lymphoid tissues, and tumors (4, 5). Camptothecin and etoposide, which are antitumor drugs, induce apoptosis of HL-60 cells in addition to numerous tumors (6 -8). We developed several monoclonal antibodies (mAbs) 1 to examine changes in nuclear architecture during this process. We screened for changes in the expression and/or localization of components of the cytoskeleton and nuclear matrix in association with apoptosis of HL-60 cells.Here, we report that the nuclear protein La is cleaved by caspase-3-like protease in the COOH terminus and that its level is increased in the cytoplasm during apoptosis. In cells, La protein binds to the oligo(U) 3Ј termini of nascent polymerase III transcripts and viral RNAs (9 -17). La protein is well known as an autoantigen, and sera from patients with rheumatoid diseases such as systemic lupus erythematosus frequently contain antibodies directed against La protein (18,19). La antigen was reported to exhibit changes in its distribution in apoptotic cells (20,21). Apoptotic cell antigens have been identified as the targets of autoantibodies in autoimmune diseases, and it has been proposed that apoptotic cells are a primary source of autoantigens (20,22). Our findings provide insight into the mechanism of redistribution of La protein during apoptosis of various types of...

Aim: The present study was conducted to define the relationship between the anti-aging effect of ubiquinol-10 supplementation and mitochondrial activation in senescence-accelerated mouse prone 1 (SAMP1) mice. Results: Here, we report that dietary supplementation with ubiquinol-10 prevents age-related decreases in the expression of sirtuin gene family members, which results in the activation of peroxisome proliferator-activated receptor c coactivator 1a (PGC-1a), a major factor that controls mitochondrial biogenesis and respiration, as well as superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2), which are major mitochondrial antioxidant enzymes. Ubiquinol-10 supplementation can also increase mitochondrial complex I activity and decrease levels of oxidative stress markers, including protein carbonyls, apurinic/apyrimidinic sites, malondialdehydes, and increase the reduced glutathione/oxidized glutathione ratio. Furthermore, ubiquinol-10 may activate Sirt1 and PGC-1a by increasing cyclic adenosine monophosphate (cAMP) levels that, in turn, activate cAMP response element-binding protein (CREB) and AMP-activated protein kinase (AMPK). Innovation and Conclusion: These results show that ubiquinol-10 may enhance mitochondrial activity by increasing levels of SIRT1, PGC-1a, and SIRT3 that slow the rate of age-related hearing loss and protect against the progression of aging and symptoms of age-related diseases.

The present study investigates whether lower-limb dominant exercise training in patients with chronic heart failure (CHF) improves endothelial function primarily in the trained lower extremities or equally in the upper and lower extremities. Twenty-eight patients with CHF were randomized to the exercise or control group. The exercise group underwent cycle ergometer training for 3 months while controls continued an inactive sedentary lifestyle. Exercise capacity (6-min walk test) and flow-mediated vasodilation in the brachial and posterior tibial arteries were evaluated. After 3 months, walking performance increased only in the exercise group (488+/-16 to 501+/-14 m [control]; 497+/-23 to 567+/-39 m [exercise, p<0.05]). The flow-mediated vasodilation in the brachial arteries did not change in either group (4.2+/-0.5 to 4.5+/-0.4% [control]; 4.3+/-0.5 to 4.6+/-0.4% [exercise]), but that in the posterior tibial arteries increased only in the exercise group (4.1+/-0.5 to 4.1+/-0.3% [control]; 3.6+/-0.3 to 6.4+/-0.6% [exercise, p<0.01]). Cycle ergometer training improved flow-mediated vasodilation in the trained lower limbs, but not in the untrained upper limbs. Exercise training appears to correct endothelial dysfunction predominantly by a local effect in the trained extremities.

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The articular cartilage from the impingement zone of hips with femoroacetabular impingement was metabolically hyperactive, supporting the concept that such impingement is a structural precursor to hip osteoarthritis.