In order to investigate bone tissue reaction to the low rigidity titanium alloy of TNTZ in bone plate fixation, animal experiment with rabbit was performed with X-ray follow-up and histological observation. Experimental fractures were made in rabbit tibiae, and fixed by different bone plates of SUS316L, Ti-6Al-4V and TNTZ. Although there was no significant difference in fracture healing, bone atrophy was observed in cortical bone especially under the bone plate, which was different in time course among three materials. The bone atrophy under the bone plate was confirmed as porous or poor bone tissue in histological observation. In addition, the diameter of the tibia bone was increased in TNTZ as the result of bone remodeling with a new cortical bone. It is confirmed that the elastic modulus of the bone plate will naturally influence bone tissue reaction to the bone plate fixation according to the Wolff's law of functional restoration.

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We have previously reported that healing of rat calvarial defects was enhanced by application of alpha tricalcium phosphate (alphaTCP) combined with simvastatin, a cholesterol synthesis inhibitor. The purpose of the present study was to investigate the cellular and molecular mechanisms in this phenomenon. Rat calvarial defects were grafted with alphaTCP with or without simvastatin or left untreated. Animals were sacrificed on 3, 7, 10, 14, and 21 days postoperatively and histological changes in the defect region were assessed. Gene expression patterns were examined by RT-PCR. Proliferation and migration of osteoprogenitor cells from the dura mater were increased in simvastatin group from day 3 to day 10 (p < 0.01). New bone formation was significantly increased in simvastatin group on day 14 and day 21 (p < 0.01). BMP-2 expression was significantly higher in simvastatin group on day 3 and day 14 (p < 0.05) and maintained until day 21. Increased upregulation of TGF-beta1 was also observed in the simvastatin group on day 7 (p < 0.05) which was maintained until day 14. These findings suggest that the proliferation and recruitment of osteoprogenitor cells were critical steps in early stage of bone healing and that these steps were enhanced by TGF-beta1 and BMP-2, which were stimulated by simvastatin.

These data suggested that simvastatin-loaded porous titanium oxide surface provides faster osseointegration and peri-implant bone formation and it would be potentially applicable in poor-quality bones.

extracellular glucose is crucially involved in the fate decision of LPS-stimulated RAW264.7 murine macrophage cells toshihiko Aki * , takeshi funakoshi, Kanako noritake, Kana Unuma & Koichi Uemura Pyroptosis, a type of inflammatory cell death, is dependent on the inflammatory caspase-mediated cleavage of gasdermin D (GSDMD), and the subsequent pore formation on plasma membranes through which interleukin (IL)-1β and IL-18 are released from cells. During proinflammatory activation, macrophages shift their metabolism from aerobic oxidative phosphorylation to anaerobic glycolysis. Hypoxia-inducible factor (HIF)1α is involved in the induction of IL-1β gene expression as well as the metabolic shift towards glycolysis. However, the relationships between pyroptosis and glycolysis, as well as between pyroptosis and HIF1α are poorly investigated. Here we show that lipopolysaccharide (LPS) stimulation of RAW264.7 murine macrophage cells results in pyroptosis when cells are cultured in high glucose medium. During pyroptosis, HIF1α activation occurs transiently followed by downregulation to sub-basal levels. HIF1α downregulation and pyroptosis are observed when cells are stimulated with LPS under high glucose conditions. We also found that intracellular levels of methylglyoxal (MGo), a side product of glycolysis, increase when cells are stimulated with LPS under high glucose conditions. The addition of glycolysis inhibitor and rapamycin suppresses HIF1α downregulation and pyroptosis. These results show that glycolysis plays a crucial role not only in pro-inflammatory activation, but also in pyroptosis in LPS-stimulated RAW264.7 macrophages. Immune cell activation, which often results in a lytic form of cell death called pyroptosis, is critical for host defense against pathogen invasions 1. Upon stimulation with lipopolysaccharides (LPS), which are components of the cell walls of gram-negative bacteria, macrophages are activated in a proinflammatory direction via the activation of inflammatory caspases. Caspase-1 is an inflammatory caspase involved in both the maturation and secretion of pro-inflammatory interleukin-1β (IL-1β) and IL-18 through plasma membrane pores 2-4. A gasdermin family protein, gasderminD (GSDMD), has been shown to be responsible for pore formation on the plasma membrane. GSDM family proteins comprise N-terminal and C-terminal domains as well as a linker connecting them. GSDMD cleavage in its linker by inflammatory caspases results in the release of the N-terminal domain (p30). GSDMD-p30 translocates to the plasma membrane where it assembles to form pores through which IL-1β and IL-18 are secreted from the cell 5-11. It has been reported that hyperglycemia is a risk factor for many illnesses including ischemic cardiovascular injuries 12 , renal diseases 13 , and sepsis 14. One of the detrimental effects of hyperglycemia on such diseases and injuries is its effect on inflammation. In response to stimulation by endotoxin and by bacterial as well as viral infection, a macrophage switches its metabolism from o...