Benefits of Substituting Sitting with Standing and Walking in Free-Living Conditions for Cardiometabolic Risk Markers, Cognition and Mood in Overweight Adults.

Background: We investigated whether substituting sitting with standing and self-perceived light walking in free-living conditions would improve cardiometabolic risk factors, mood, and cognition in overweight/obese adults. Methods: In a randomized, cross-over study, 24 (m/f: 13/11) sedentary overweight/obese participants (64 ± 7 years, BMI 29 ± 2 kg/m2) followed two activity regimens of each 4 days in free-living conditions: "Sit": sitting 13.5 h/day, standing 1.4 h/day, self-perceived light-intensity walking 0.7 h/day; for "SitLess" these activities lasted 7.6, 4.0, and 4.3 h/day, respectively. Meals were standardized and physical activity was assessed by accelerometry (activPAL). Insulin sensitivity (expressed as Matsuda-index based on an oral glucose tolerance test), circulating lipids, blood pressure, mood (pleasantness and arousal), and cognition were assessed on the morning after the activity regimens. Quality of life and sleep were assessed on the last day of the activity regimens. Results: We observed that AUC (0-190 min) for insulin decreased by 20% after SitLess vs. Sit [10,125 (656) vs. 12,633 (818); p = 0.006]. Insulin sensitivity improved by 16% after SitLess vs. Sit [Matsuda-index, mean (SEM): 6.45 (0.25) vs. 5.58 (0.25) respectively; p = 0.007]. Fasting triglycerides, non-HDL-cholesterol, and apolipoprotein B decreased by 32, 7, and 4% respectively, whereas HDL-cholesterol increased by 7% after SitLess vs. Sit (all p < 0.01). Diastolic blood pressure was lower after SitLess vs. Sit (p < 0.05). Pleasantness (as one marker of mood status) after the oral glucose tolerance test was higher after SitLess vs. Sit (p < 0.05). There was no significant difference between regimens for cognition, quality of life and sleep. Conclusions: Reducing sitting time in free-living conditions markedly improved insulin sensitivity, circulating lipids, and diastolic blood pressure. Substituting sitting with standing and self-perceived light walking is an effective strategy to improve cardiometabolic risk factors in overweight/obese subjects.

Differential cell viability of chondrocytes and progenitor cells in tissue-engineered constructs following implantation into osteochondral defects.

Animal studies in cartilage tissue engineering usually include the transfer of cultured cells into chondral or osteochondral defects. Immediately at implantation, the cells are exposed to a dramatically changed environment. The aim of this study was to determine the viability of two cell types currently considered for cellular therapies of cartilage defects-chondrocytes and progenitor cells-shortly after exposure to an osteochondral defect in rabbit knees. To that end, autogenic chondrocytes and periosteal cells were labeled with CM-DiI fluorochrome, seeded or cultured in PEGT/PBT scaffolds for periods up to 2 weeks, transferred into osteochondral defects, harvested 5 days postimplantation, and analyzed for cell viability. In order to further elucidate factors effecting cell viability within our model system, we investigated the effect of serum, 2) extracellular matrix surrounding implanted cells, 3) scaffold interconnectivity, and 4) hyaluronan, as a known cell protectant. Controls included scaffolds with devitalized cells and scaffolds analyzed at implantation. We found that the viability of periosteum cells (14%), but not of chondrocytes (65-95%), was significantly decreased after implantation. The addition of hyaluronan increased periostium cell viability to 44% (p < 0.05). Surprisingly, cell viability in less interconnected compression-molded scaffolds was higher compared to that of fully interconnected scaffolds produced by rapid prototyping. All other factors tested did not affect viability significantly. Our data suggest chondrocytes as a suitable cell source for cartilage repair in line with clinical data on several chondrocyte-based therapies. Although we did not test progenitor cells other the periosteum cells, tissue-engineering approaches using such cell types should take cell viability aspects into consideration.

Repair of osteochondral defects in rabbits with ectopically produced cartilage.

Cartilage has poor regenerative capacity. Donor site morbidity and interference with joint homeostasis should be considered when applying the autologous chondrocyte transplantation technique. The use of ectopically produced cartilage, derived from periosteum, might be a novel method to heal cartilage defects. Ectopic cartilage was produced by dissecting a piece of periosteum from the tibia of rabbits. After 14 days the reactive tissue at the dissection site was harvested and a graft was cored out and press-fit implanted in an osteochondral defect in the medial condyle of the femur with or without addition of hyaluronan. After 3 weeks and 3 months the repair reaction was evaluated by histology. Thionine- and collagen type II-stained sections were evaluated for graft viability, ingrowth of the graft, and joint surface repair. Empty defects remained empty 3 weeks after implantation, ectopic cartilage filled the defect to the level of the surrounding cartilage. Histologically, the grafts were viable, consisting mainly of cartilage, and showed a variable pattern of ingrowth. Three months after implantation empty defects with or without hyaluronan were filled primarily with fibrocartilaginous tissue. Defects treated with ectopic cartilage contained mixtures of fibrocartilaginous and hyaline cartilage. Sometimes a tidemark was observed in the new articular cartilage and the orientation of the cells resembled that of healthy articular cartilage. Subchondral bone repair was excellent. The modified O'Driscoll scores for empty defects without and with hyaluronan were 12.7 +/- 6.4 and 15.3 +/- 3.2; for treated defects scores were better (15.4 +/- 3.9 and 18.2 +/- 2.9). In this conceptual study the use of ectopic cartilage derived from periosteum appears to be a promising novel method for joint surface repair in rabbits.