Lipin1 expression was induced at a late stage of differentiation of 3T3-L1 preadipocytes and maintained at high levels in mature adipocytes. Knockdown of expression of lipin1 by small interfering RNA in 3T3-L1 preadipocytes almost completely inhibited differentiation into adipocytes, whereas overexpression of lipin1 accelerated adipocyte differentiation, demonstrating that lipin1 is required for adipocyte differentiation. In mature adipocytes, transfection of lipin1-small interfering RNA decreased the expression of adipocyte functional genes, indicating the involvement of lipin1 in the maintenance of adipocyte function. Lipin1 increases the transcription-activating function of peroxisome proliferator-activated receptor ␥ 2 (PPAR␥ 2 ) via direct physical interaction, whereas lipin1 did not affect the function of other adipocyte-related transcription factors such as C/EBP␣, liver X-activated receptor ␣, or sterol regulatory element binding protein 1c. In mature adipocytes, lipin1 was specifically recruited to the PPAR␥-response elements of the phosphoenolpyruvate carboxykinase gene, an adipocyte-specific gene. C/EBP␣ up-regulates lipin1 transcription by directly binding to the lipin1 promoter. Based on the existence of a positive feedback loop between C/EBP␣ and PPAR␥ 2 , we propose that lipin1 functions as an amplifier of the network between these factors, resulting in the maintenance of high levels of the specific gene expression that are required for adipogenesis and mature adipocyte functions.Adipose tissue plays an essential role in maintaining metabolic homeostasis (1). White adipose tissue takes up fatty acids derived from the diet or the liver as well as increases the uptake of glucose in response to insulin by recruiting glucose transporter 4 (GLUT4) 2 to the plasma membrane. Then white adipose tissue stores the glucose or fatty acids as a form of triacylglyceride and releases free fatty acids during states of starvation. Recent studies have shown that adipose tissue secretes various humoral factors called adipocytokines which play numerous functions associated with food intake, insulin sensitivity, energy homeostasis, inflammatory responses, and atherogenesis (2). In obese subjects adipocytes cannot function adequately, thereby causing various metabolic syndromes including insulin resistance, dyslipidemia, and coronary-vascular disease (3-6). Lipodystrophy leads to the same condition as obesity due to lack of adipocyte function (7-9). Thus, studying the molecular mechanisms that control adipose tissue development and function is important for understanding the pathophysiology of metabolic syndromes.Adipogenesis is a process in which premature cells acquire adipocyte-specific functions. A complex network of transcription factors is developed during this process in response to extracellular adipogenic stimuli. In 3T3-L1 preadipocyte cells the CCAAT/enhancer-binding proteins  and ␦ (C/EBP and C/EBP␦) are induced immediately upon adipogenic hormonal stimuli, and they are expressed for approximately 2 days ...
In this study, a poly(e-caprolactone) (PCL)/bioactive glass (BG) nanocomposite was fabricated using BG nanofibers (BGNFs) and compared with an established composite fabricated using microscale BG particles. The BGNFs were generated using sol-gel precursors via the electrospinning process, chopped into short fibers and then incorporated into the PCL organic matrix by dissolving them in a tetrahydrofuran solvent. The biological and mechanical properties of the PCL/BGNF composites were evaluated and compared with those of PCL/BG powder (BGP). Because the PCL/BG composite containing 20 wt % BG showed the highest level of alkaline phosphatase (ALP) activity, all evaluations were performed at this concentration except for that of the ALP activity itself. In vitro cell tests using the MC3T3 cell line demonstrated the enhanced biocompatibility of the PCL/BGNF composite compared with the PCL/BGP composite. Furthermore, the PCL/BGNF composite showed a significantly higher level of bioactivity compared with the PCL/BGP composite. In addition, the results of the in vivo animal experiments using Sprague-Dawley albino rats revealed the good bone regeneration capability of the PCL/BGNF composite when implanted in a calvarial bone defect. In the result of the tensile test, the stiffness of the PCL/BG composite was further increased when the BGNFs were incorporated. These results indicate that the PCL/BGNF composite has greater bioactivity and mechanical stability when compared with the PCL/BG composite and great potential as a bone regenerative material. '
We herein propose a novel way of producing nanofibrous gelatin-silica hybrid scaffolds through thermally induced phase-separation (TIPS) particularly using mixtures of gelatin solution and silica sol, which can mimic the physical structure, chemical composition, and eventually functions of the native bone extracellular matrix (ECM). The gelatin solutions were homogeneously hybridized with various contents of a silica sol using simple magnetic stirring, which enabled the construction of a nanofibrous structure with a uniform distribution of the silica in the gelatin nanofibers. The nanofibrous gelatinsilica hybrid scaffolds showed much better mechanical properties and in vitro biodegradation stability and apatite-forming ability than the nanofibrous pure gelatin scaffold, which were achieved by the presence of a stiff, bioactive silica phase in the nanofibers and the interaction between the silica hydroxyls and the amino group in the gelatin polymer. In addition, the nanofibrous gelatin-silica hybrid scaffold with a silica content of 30 wt% showed reasonably high in vitro biocompatibility. These findings suggest that the highly porous, nanofibrous hybrid structure mimicking the bone ECM can provide an excellent matrix for bone tissue regeneration.
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