Comparison of magnesium alloys and poly-l-lactide screws as degradable implants in a canine fracture model.

The aims of this study were to evaluate in vivo the biological responses to implants composed of biodegradable anodized WE43 (containing magnesium yttrium, rare earth elements and zirconium; Elektron SynerMag®) magnesium alloy, monolithic WE43 magnesium alloy and poly-l-lactic acid (PLLA), which are commonly used materials in clinic settings, and to evaluate the effectiveness of the materials as bone screws. The effectiveness of the magnesium alloy implants in osteosynthesis was evaluated using a bone fracture model involving the tibia of beagle dogs. For the monolithic WE43 implants, radiological, and histological evaluation revealed that bone trabeculae around the implanted monolithic WE43 decreased because of an inflammatory response. However, there was no damage due to hydrogen gas or inflammatory response in the bone tissue around the anodized WE43 implants. After 4 weeks, all the PLLA implants (n = 3) had broken but the WE43 implants had not (n = 6). These results suggest that the WE43 implants had sufficient strength to fix bone fractures at load-bearing sites in orthopedic and oral maxillofacial surgery. Therefore, these biodegradable magnesium alloys are good candidates for replacing biodegradable polymers. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1282-1289, 2016.

Cell cycle gene-specific control of transcription has a critical role in proliferation of primordial germ cells.

Transcription elongation is stimulated by positive transcription elongation factor b (P-TEFb), for which activity is repressed in the 7SK small nuclear ribonucleoprotein (7SK snRNP) complex. We show here a critical role of 7SK snRNP in growth control of primordial germ cells (PGCs). The expression of p15(INK4b), a cyclin-dependent kinase inhibitor (CDKI) gene, in PGCs is selectively activated by P-TEFb and its recruiting molecule, Brd4, when the amount of active P-TEFb is increased due to reduction of the 7SK snRNP, and PGCs consequently undergo growth arrest. These results indicate that CDKI gene-specific control of transcription by 7SK snRNP plays a pivotal role in the maintenance of PGC proliferation.

REST and its downstream molecule Mek5 regulate survival of primordial germ cells.

In mouse embryos, some primordial germ cells (PGCs) are eliminated by apoptosis, but the molecular pathways that lead to PGC survival versus apoptosis have not been fully characterized. Here, we found that REST (repressor element 1-silencing transcription factor), a transcription factor that binds a conserved regulatory element, NRSE/RE1, played a role in PGC survival. REST expression was higher in PGCs than in surrounding somatic cells. Moreover, in mouse embryos with a PGC-specific conditional REST mutation, the PGC population experienced more apoptosis and was significantly smaller than that in control embryos; these findings indicated that REST functioned in a cell-autonomous fashion that was critical for PGC survival. Several anti-apoptotic genes were among the previously identified REST-target gene candidates; moreover, some of these genes were downregulated in the REST-deficient PGCs. Mek5, which encodes a component in the a MAP kinase cascade, was one of these downregulated REST-target gene candidates, and a Mek5 mutation, like the REST mutation, caused an increase in PGC apoptosis; these finding suggested that REST promoted PGC survival via regulation of the Mek5 expression. Importantly, there were a normal number of PGCs in the REST mutants at birth, and both the male and female REST-mutant adults were fertile; these final observations revealed that the PGC population was very robust and could recover from a genetically induced reduction in cell number.