An exploratory study on the impact of static and dynamic sitting postures on lumbar and pelvic mobility during visual display terminal work.

[Purpose] Limited studies exist on the impact of sustained work at a visual display terminal (VDT) on the position and motion of the pelvis and lumbar spine. We evaluated the changes in movement of the lumbar column and pelvis during VDT work. [Participants and Methods] We evaluated the sitting posture of 20 healthy adults while they performed VDT work. The effects of the sitting posture on lumbo-pelvic position and motion were captured using a three-dimensional accelerometer. Between-posture effects of VDT work were evaluated using an analysis of variance (ANOVA). A two-way ANOVA was used to assess the root mean square (RMS) values of the 80-min VDT work period for each posture. A one-way ANOVA was used to evaluate pre- and post-work changes in RMS values during the finger floor distance test (FFD). [Results] People in the dynamic sitting balance chair (DSBC)-based posture demonstrated significantly higher pelvic RMS values than those in reclining and upright sitting postures. The DSBC-based posture was also associated with significantly higher pre- and post-work lumbar and pelvic RMS values during the FFD than in the reclining and upright sitting postures. [Conclusion] The dynamic balance chair may be an effective method of establishing a pattern of spinal exercise during prolonged sitting.

SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix.

SP7/Osterix (OSX) is a master regulatory transcription factor that activates a variety of genes during differentiation of osteoblasts. However, the influence of post-translational modifications on the regulation of its transactivation activity is largely unknown. Here, we report that sirtuins, which are NAD(+)-dependent deacylases, regulate lysine deacylation-mediated transactivation of OSX. Germline Sirt7 knockout mice develop severe osteopenia characterized by decreased bone formation and an increase of osteoclasts. Similarly, osteoblast-specific Sirt7 knockout mice showed attenuated bone formation. Interaction of SIRT7 with OSX leads to the activation of transactivation by OSX without altering its protein expression. Deacylation of lysine (K) 368 in the C-terminal region of OSX by SIRT7 promote its N-terminal transactivation activity. In addition, SIRT7-mediated deacylation of K368 also facilitates depropionylation of OSX by SIRT1, thereby increasing OSX transactivation activity. In conclusion, our findings suggest that SIRT7 has a critical role in bone formation by regulating acylation of OSX.

TET2-dependent IL-6 induction mediated by the tumor microenvironment promotes tumor metastasis in osteosarcoma.

The tumor microenvironment promotes epigenetic changes in tumor cells associated with tumor aggressiveness. Here we report that in primary tumor cells, increased interleukin-6 (IL-6) expression brought on by DNA demethylation of its promoter by ten-eleven translocation 2 (TET2) promotes lung metastasis in osteosarcoma (OS). Xenograft experiments show increased IL-6 expression and decreased methylation of its promoter in OS cells after implantation relative to before implantation. In addition, changes in IL-6 methylation and expression seen in OS cells at the primary site were maintained at the metastatic site. TET2 knockdown in OS cells suppressed upregulation of IL-6 and demethylation of its promoter in xenograft tumors and decreased tumor metastasis. We also present evidence showing that tumor cell-derived IL-6 facilitates glycolytic metabolism in tumor cells by activating the MEK/ERK1/2/hypoxia-inducible transcription factor-1α (HIF-1α) pathway and increases lung colonization by OS cells by upregulating expression of intercellular adhesion molecule-1 (ICAM-1), enhancing tumor metastasis. Blocking IL-6 signaling with a humanized monoclonal antibody against the IL-6 receptor reduced lung metastasis and prolonged survival of xenografted mice. These findings suggest that TET2-dependent IL-6 induction enables acquisition of aggressive phenotypes in OS cells via the tumor microenvironment and that blocking IL-6 signaling could be serve as a potential therapy to antagonize metastasis.

SIRT7 is an important regulator of cartilage homeostasis and osteoarthritis development.

Sirtuins (SIRT1-7) are NAD+-dependent deacetylase/deacylases that regulate a wide variety of biological functions. Although the roles of sirtuins in cartilage homeostasis and cartilage diseases have been well studied, there is no information on the contribution of SIRT7 to cartilage homeostasis and osteoarthritis (OA) pathologies. Here, we demonstrate that Sirt7 knockout mice are resistant to the development of aging-associated OA and forced exercise-induced OA. Attenuation of Sirt7 in the murine chondrogenic cell line ATDC5 increased the deposition of a glycosaminoglycan-rich extracellular matrix and the mRNA expression of extracellular matrix components such as Col2a1 and Acan. Mechanistically, we found that SIRT7 suppressed the transcriptional activity of SOX9, which is an important transcription factor in chondrocytes, and that the enzymatic activity of SIRT7 was required for its function. Our results indicate that SIRT7 is a novel important regulator of cartilage homeostasis and OA development.

Electromyographic analysis of relevant muscle groups during completion of computer tasks using different computer mouse positions.

BACKGROUND: We analyzed muscular activity for different computer mouse positions during the completion of a timed computer task and determined whether the different mouse positions could affect muscular activity, productivity and perceived fatigue. METHODS: The subjects were nine healthy young men. Two mouse positions were studied: the distal position (DP), with the forearm rested on the desk; the proximal position (PP), with only the wrist rested on the desk. The subjects performed a 16-min task in each position. Surface electromyography data were recorded for the upper back and shoulder muscles. Work productivity and muscular activity were measured for each mouse position. A visual analog scale was used to assess subjective fatigue. RESULTS: Muscular activity was higher in muscle (m.) deltoideus (posterior) for the DP, while it was significantly higher in m. inferior infraspinatus for the PP. The visual analog scale score was significantly higher and work productivity was lower in the PP. CONCLUSIONS: We found that using a mouse in the DP rather than the PP leads to less activity of the external rotators, less perceived fatigue and more productivity. This suggests that the DP is preferable to the PP for computer work involving a mouse.

Effects of a dynamic chair on pelvic mobility, fatigue, and work efficiency during work performed while sitting: a comparison of dynamic sitting and static sitting.

[Purpose] Working while sitting for long periods can cause lumbar pain, fatigue, and reduced work efficiency. How a dynamic chair with a seat that moves three-dimensionally affects pelvic mobility before and after work, work efficiency, and post-work fatigue were examined. [Subjects and Methods] Subjects were 17 healthy adults (10 males, 7 females, mean age 21.8 ± 2.7 years). Subjects performed a 30-min Kraepelin test under two conditions: sitting in a standard office chair and sitting in a dynamic sitting balance chair. Root mean square (RMS) values of pelvic movement measured by a triaxial accelerometer during 30 minutes of work, finger-floor distance before and after work, lumbar fatigue, and pelvic movement RMS values during finger-floor distance measurement were used as outcome measures. [Results] Pelvic movement RMS values collected every 5 minutes during 30 minutes of work were significantly higher while sitting in the dynamic balance chair. Changes in pelvic movement RMS values during finger-floor distance measurement after work and amount of work performed during 30 minutes were significantly higher and lumbar fatigue was significantly lower for the dynamic balance chair. [Conclusion] Dynamic sitting maintained or increased pelvic flexibility. The dynamic balance chair may effectively help workers work continuously in seated postures with little fatigue.

Mice Deficient in Angiopoietin-like Protein 2 (Angptl2) Gene Show Increased Susceptibility to Bacterial Infection Due to Attenuated Macrophage Activity.

Macrophages play crucial roles in combatting infectious disease by promoting inflammation and phagocytosis. Angiopoietin-like protein 2 (ANGPTL2) is a secreted factor that induces tissue inflammation by attracting and activating macrophages to produce inflammatory cytokines in chronic inflammation-associated diseases such as obesity-associated metabolic syndrome, atherosclerosis, and rheumatoid arthritis. Here, we asked whether and how ANGPTL2 activates macrophages in the innate immune response. ANGPTL2 was predominantly expressed in proinflammatory mouse bone marrow-derived differentiated macrophages (GM-BMMs) following GM-CSF treatment relative to anti-inflammatory cells (M-BMMs) established by M-CSF treatment. Expression of the proinflammatory markers IL-1ß, IL-12p35, and IL-12p40 significantly decreased in GM-BMMs from Angptl2-deficient compared with wild-type (WT) mice, suggestive of attenuated proinflammatory activity. We also report that ANGPTL2 inflammatory signaling is transduced through integrin α5ß1 rather than through paired immunoglobulin-like receptor B. Interestingly, Angptl2-deficient mice were more susceptible to infection with Salmonella enterica serovar Typhimurium than were WT mice. Moreover, nitric oxide (NO) production by Angptl2-deficient GM-BMMs was significantly lower than in WT GM-BMMs. Collectively, our findings suggest that macrophage-derived ANGPTL2 promotes an innate immune response in those cells by enhancing proinflammatory activity and NO production required to fight infection.

ANGPTL2 increases bone metastasis of breast cancer cells through enhancing CXCR4 signaling.

Bone metastasis of breast cancer cells is a major concern, as it causes increased morbidity and mortality in patients. Bone tissue-derived CXCL12 preferentially recruits breast cancer cells expressing CXCR4 to bone metastatic sites. Thus, understanding how CXCR4 expression is regulated in breast cancer cells could suggest approaches to decrease bone metastasis of breast tumor cells. Here, we show that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) increases responsiveness of breast cancer cells to CXCL12 by promoting up-regulation of CXCR4 in those cells. In addition, we used a xenograft mouse model established by intracardiac injection of tumor cells to show that ANGPTL2 knockdown in breast cancer cells attenuates tumor cell responsiveness to CXCL12 by decreasing CXCR4 expression in those cells, thereby decreasing bone metastasis. Finally, we found that ANGPTL2 and CXCR4 expression levels within primary tumor tissues from breast cancer patients are positively correlated. We conclude that tumor cell-derived ANGPTL2 may increase bone metastasis by enhancing breast tumor cell responsiveness to CXCL12 signaling through up-regulation of tumor cell CXCR4 expression. These findings may suggest novel therapeutic approaches to treat metastatic breast cancer.

Angiopoietin-like protein 2 renders colorectal cancer cells resistant to chemotherapy by activating spleen tyrosine kinase-phosphoinositide 3-kinase-dependent anti-apoptotic signaling.

Angiopoietin-like protein 2 (ANGPTL2) plays an important role in inflammatory carcinogenesis and tumor metastasis by activating tumor angiogenesis and tumor cell chemotaxis and invasiveness. However, it is unclear whether ANGPTL2 expression has an effect on tumor cell survival. Here, we explored that possibility by determining whether ANGPTL2 expression altered survival of human colorectal cancer cell lines treated with antineoplastic drugs. To do so, we generated SW480 cells expressing ANGPTL2 (SW480/ANGPTL2) and control (SW480/Ctrl) cells. Apoptosis induced by antineoplastic drug treatment was significantly decreased in SW480/ANGPTL2 compared to control cells. Expression of anti-apoptotic BCL-2 family genes was upregulated in SW480/ANGPTL2 compared to SW480/Ctrl cells. To assess signaling downstream of ANGPTL2 underlying this effect, we carried out RNA sequencing analysis of SW480/ANGPTL2 and SW480/Ctrl cells. That analysis, combined with in vitro experiments, indicated that Syk-PI3K signaling induced expression of BCL-2 family genes in SW480/ANGPTL2 cells. Furthermore, ANGPTL2 increased its own expression in a feedback loop by activating the spleen tyrosine kinase-nuclear factor of activated T cells (Syk-NFAT) pathway. Finally, we observed a correlation between higher ANGPTL2 expression in primary unresectable tumors from colorectal cancer patients who underwent chemotherapy with a lower objective response rate. These findings suggest that attenuating ANGPTL2 signaling in tumor cells may block tumor cell resistance to antineoplastic therapies.

The position of a standard optical computer mouse affects cardiorespiratory responses during the operation of a computer under time constraints.

OBJECTIVES: This study investigated the association between task-induced stress and fatigue by examining the cardiovascular responses of subjects using different mouse positions while operating a computer under time constraints. MATERIAL AND METHODS: The study was participated by 16 young, healthy men and examined the use of optical mouse devices affixed to laptop computers. Two mouse positions were investigated: (1) the distal position (DP), in which the subjects place their forearms on the desk accompanied by the abduction and flexion of their shoulder joints, and (2) the proximal position (PP), in which the subjects place only their wrists on the desk without using an armrest. The subjects continued each task for 16 min. We assessed differences in several characteristics according to mouse position, including expired gas values, autonomic nerve activities (based on cardiorespiratory responses), operating efficiencies (based on word counts), and fatigue levels (based on the visual analog scale - VAS). RESULTS: Oxygen consumption (VO(2)), the ratio of inspiration time to respiration time (T(i)/T(total)), respiratory rate (RR), minute ventilation (VE), and the ratio of expiration to inspiration (Te/T(i)) were significantly lower when the participants were performing the task in the DP than those obtained in the PP. Tidal volume (VT), carbon dioxide output rates (VCO(2)/VE), and oxygen extraction fractions (VO(2)/VE) were significantly higher for the DP than they were for the PP. No significant difference in VAS was observed between the positions; however, as the task progressed, autonomic nerve activities were lower and operating efficiencies were significantly higher for the DP than they were for the PP. CONCLUSIONS: Our results suggest that the DP has fewer effects on cardiorespiratory functions, causes lower levels of sympathetic nerve activity and mental stress, and produces a higher total workload than the PP. This suggests that the DP is preferable to the PP when operating a computer.