Tensile strain increases expression of CCN2 and COL2A1 by activating TGF-beta-Smad2/3 pathway in chondrocytic cells

Physiologic mechanical stress stimulates expression of chondrogenic genes, such as multifunctional growth factor CYR61/CTGF/NOV (CCN) 2 and alpha 1(II) collagen (COL2A1), and maintains cartilage home-ostasis. In our previous studies, cyclic tensile strain (CTS) induces nuclear translocation of transforming growth factor (TGF)-beta receptor-regulated Smad2/3 and the master chondrogenic transcription factor Srytype HMG box (SOX) 9. However, the precise mechanism of stretch-mediated Smad activation remains unclear in transcriptional regulation of CCN2 and COL2A1. Here we hypothesized that CTS may induce TGF-beta 1 release and stimulate Smad-dependent chondrogenic gene expression in human chondrocytic SW1353 cells. Uni-axial CTS (0.5 Hz, 5% strain) stimulated gene expression of CCN2 and COL2A1 in SW1353 cells, and induced TGF-beta 1 secretion. CCN2 synthesis and nuclear translocalization of Smad2/3 and SOX9 were stimulated by CTS. In addition, CTS increased the complex formation between phosphorylated Smad2/3 and SOX9. The CCN2 promoter activity was cooperatively enhanced by CIS and Smad3 in luciferase reporter assay. Chromatin immunoprecipitation revealed that CTS increased Smad2/3 interaction with the CCN2 promoter and the COL2A1 enhancer. Our results suggest that CTS epigenetically stimulates CCN2 transcription via TGF-beta 1 release associated with Smad2/3 activation and enhances COL2A1 expression through the complex formation between SOX9 and Smad2/3

Effective theoretical approach of Gauge-Higgs unification model and its phenomenological applications

We derive the low energy effective theory of Gauge-Higgs unification (GHU) models in the usual four dimensional framework. We find that the theories are described by only the zero-modes with a particular renormalization condition in which essential informations about GHU models are included. We call this condition ``Gauge-Higgs condition'' in this letter. In other wards, we can describe the low energy theory as the SM with this condition if GHU is a model as the UV completion of the Standard Model. This approach will be a powerful tool to construct realistic models for GHU and to investigate their low energy phenomena.Comment: 18 pages, 2 figures; Two paragraphs discussing the applicable scope of this approach are adde

Nonexponential decay of an unstable quantum system: Small-QQ-value s-wave decay

We study the decay process of an unstable quantum system, especially the deviation from the exponential decay law. We show that the exponential period no longer exists in the case of the s-wave decay with small $Q$ value, where the $Q$ value is the difference between the energy of the initially prepared state and the minimum energy of the continuous eigenstates in the system. We also derive the quantitative condition that this kind of decay process takes place and discuss what kind of system is suitable to observe the decay.Comment: 17 pages, 6 figure

Kidney transplantation recovers the reduction level of serum sulfatide in ESRD patients via processes correlated to oxidative stress and platelet count

Sulfatide is a major component of glycosphingolipids in lipoproteins. Recently, we reported that a low serum level of sulfatide in hemodialysis patients might be related to the high incidence of cardiovascular diseases. However, the serum kinetics of sulfatide in kidney disease patients and the function of endogenous serum sulfatide are still unclear. To obtain novel knowledge concerning these issues, we investigated the serum kinetics of sulfatide in 5 adult kidney transplant recipients. We also analyzed the correlated factors influencing the serum sulfatide level, using multiple regression analysis. Kidney transplantation caused a dramatic increase of serum sulfatide without an alteration of its composition in all recipients in a time-dependent manner; however, the recovery speed was slower than that of the improvement of kidney function and the serum sulfatide reached a nearly normal level after 1 year. Multiple regression analysis showed that the significant correlated factor influencing the serum sulfatide level was log duration (time parameter) throughout the observation period, and the correlated factors detected in the stable phase were the decrease of serum concentration of malondialdehyde (an oxidative stress marker) as well as the elevation of platelet count. The current study results demonstrated the gradual but reliable recovery of the serum sulfatide level in kidney transplant recipients for the first time, suggesting a close correlation between serum sulfatide and kidney function. The recovery of serum sulfatide might derive from the attenuation of systemic oxidative stress. The normal level of serum sulfatide in kidney transplant recipients might affect platelet function, and contribute to the reduction of cardiovascular disease incidence.ArticleGLYCOCONJUGATE JOURNAL. 28(3-4):125-135 (2011)journal articl

Adipose-Derived Extract Suppresses IL-1 beta-Induced Inflammatory Signaling Pathways in Human Chondrocytes and Ameliorates the Cartilage Destruction of Experimental Osteoarthritis in Rats

We investigated the effects of adipose-derived extract (AE) on cultured chondrocytes and in vivo cartilage destruction. AE was prepared from human adipose tissues using a nonenzymatic approach. Cultured human chondrocytes were stimulated with interleukin-1 beta (IL-1 beta) with or without different concentrations of AE. The effects of co-treatment with AE on intracellular signaling pathways and their downstream gene and protein expressions were examined using real-time PCR, Western blotting, and immunofluorescence staining. Rat AE prepared from inguinal adipose tissues was intra-articularly delivered to the knee joints of rats with experimental osteoarthritis (OA), and the effect of AE on cartilage destruction was evaluated histologically. In vitro, co-treatment with IL-1 beta combined with AE reduced activation of the p38 and ERK mitogen-activated protein kinase (MAPK) pathway and nuclear translocation of the p65 subunit of nuclear factor-kappa B (NF-kappa B), and subsequently downregulated the expressions of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, IL-6, and IL-8, whereas it markedly upregulated the expression of IL-1 receptor type 2 (IL-1R2) in chondrocytes. Intra-articular injection of homologous AE significantly ameliorated cartilage destruction six weeks postoperatively in the rat OA model. These results suggested that AE may exert a chondroprotective effect, at least in part, through modulation of the IL-1 beta-induced inflammatory signaling pathway by upregulation of IL-1R2 expression

Effective Potential of Higgs Field in Warped Gauge-Higgs Unification

The gauge-Higgs unification is one of influential scenarios to solve the hierarchy problem in the Standard Model. Recently, the scenario on the warped background attracts many attentions due to a large possibility to construct a realistic model naturally in this framework. It is, however, well known that the effective potential for the Higgs field, which is the most important prediction of the scenario, is not easy to calculate on the warped background, because masses of Kaluza-Klein particles are not obtained analytically. In this article, we derive useful formulae for the effective potential. The formulae allow us to calculate the Higgs mass easily, thus to construct a realistic model in the gauge-Higgs unification scenario on the warped background. Using obtained formulae, we calculate contributions from bulk fermions with several boundary conditions. We also show bulk fermions, which have boundary conditions not allowed in the orbifold picture, do not contribute to the effective potential.Comment: 28 pages, 6 figure