Tet2 Regulates Osteoclast Differentiation by Interacting with Runx1 and Maintaining Genomic 5-Hydroxymethylcytosine(5hmC)

As a dioxygenase. Ten-Eleven Translocation 2 （TET2） catalyzes subsequent steps of 5-methylcytosine （5mC） oxidation. TET2 plays a critical role in the self-renewal, proliferation, and differentiation of hei-natopoietic stem cells, but its impact on mature hematopoietic cells is not well-characterized. Here we show that Tet2 plays an essential role in osteoclastogenesis. Dele- tion of Tet2 impairs the differentiation of osteoclast precursor cells （macrophages） and their matu- ration into bone-resorbing osteoclasts in vitro. Furthermore, Tet2 / mice exhibit mild osteopetrosis, accompanied by decreased number of osteoclasts in vivo. Tet2 loss in macrophages results in the altered expression of a set of genes implicated in osteoclast differentiation, such as Cehpa, Mafb, and Nfkbiz. Tet2 deletion also leads to a genome-wide alteration in the level of 5-hydroxymethylcytosine （ShmC） and altered expression of a specific subset of macrophage genes associated with osteoclast differentiation. Furthermore, Tet2 interacts with Runxl and negatively modulates its transcriptional activity. Our studies demonstrate a novel molecular mechanism controlling osteoclast differentiation and function by Tet2, that is, through interactions with Runxl and the maintenance of genomie 5hmC. Targeting Tet2 and its pathway could be a potential therapeutic strategy for the prevention and t,＇eatment of abnormal bone mass caused by the deregulation of osteoclast activities.

Reduction of die roll height in duplex gears through a sheet-bulk metal forming method

In the existing shearing processes for fabricating parts such as duplex gears, die roll is difficult to avoid. Accordingly, a method based on sheet-bulk metal forming for fabricating a duplex gear with extremely small die roll in one stroke is proposed in the current work. The process could be divided into three stages according to the forming features: upsetting and shearing stage, lateral extrusion stage, and local filling stage. The die roll appeared in the shearing stage, which could be reduced in the subsequent extrusion and local filling stages. To reveal the underground mechanism, material flows under two situations, as a key factor to influence the forming quality, were compared and investigated. The results revealed that by controlling material flow, one could avoid the defects and reduce the die roll.