The Beneficial Effects of Bisphosphonate-enoxacin on Cortical Bone Mass and Strength in Ovariectomized Rats

Osteoporosis is a major age-related bone disease characterized by low bone mineral density and a high risk of fractures. Bisphosphonates are considered as effective agents treating osteoporosis. However, long-term use of bisphosphonates is associated with some serious side effects, which limits the widespread clinical use of bisphosphonates. Here, we demonstrate a novel type of bone-targeting anti-resorptive agent, bisphosphonate-enoxacin (BE). In this study, ovariectomized rat model was established and treated with PBS, zoledronate (50 μg/kg) and different dose of BE (5 mg/kg and 10 mg/kg), respectively. The rats subjected to sham-operation and PBS treatment were considered as control group. Then, micro-computed tomography scanning, biomechanical tests, nano-indentation test and Raman analysis were used to compare the effects of zoledronate and BE on cortical bone mass, strength, and composition in ovariectomized rats. We found that both zoledronate and BE were beneficial to cortical bone strength. Three-point bending and nano-indentation tests showed that zoledronate- and BE-treated groups had superior general and local biomechanical properties compared to the ovariectomized groups. Interestingly, it seemed that BE-treated group got a better biomechanical property than the zoledronate-treated group. Also, BE-treated group showed significantly increased proteoglycan content compared with the zoledronate-treated group. We hypothesized that the increased bone strength and biomechanical properties was due to altered bone composition after treatment with BE. BE, a new bone-targeting agent, may be considered a more suitable anti-resorptive agent to treat osteoporosis and other bone diseases associated with decreased bone mass

Nucleotide diversity and molecular evolution of the WAG-2 gene in common wheat (Triticum aestivum L) and its relatives

In this work, we examined the genetic diversity and evolution of the WAG-2 gene based on new WAG-2 alleles isolated from wheat and its relatives. Only single nucleotide polymorphisms (SNP) and no insertions and deletions (indels) were found in exon sequences of WAG-2 from different species. More SNPs and indels occurred in introns than in exons. For exons, exons+introns and introns, the nucleotide polymorphism π decreased from diploid and tetraploid genotypes to hexaploid genotypes. This finding indicated that the diversity of WAG-2 in diploids was greater than in hexaploids because of the strong selection pressure on the latter. All dn/ds ratios were < 1.0, indicating that WAG-2 belongs to a conserved gene affected by negative selection. Thirty-nine of the 57 particular SNPs and eight of the 10 indels were detected in diploid species. The degree of divergence in intron length among WAG-2 clones and phylogenetic tree topology suggested the existence of three homoeologs in the A, B or D genome of common wheat. Wheat AG-like genes were divided into WAG-1 and WAG-2 clades. The latter clade contained WAG-2, OsMADS3 and ZMM2 genes, indicating functional homoeology among them

Comparative high-resolution mapping of the wax inhibitors Iw1 and Iw2 in hexaploid wheat.

The wax (glaucousness) on wheat leaves and stems is mainly controlled by two sets of genes: glaucousness loci (W1 and W2) and non-glaucousness loci (Iw1 and Iw2). The non-glaucousness (Iw) loci act as inhibitors of the glaucousness loci (W). High-resolution comparative genetic linkage maps of the wax inhibitors Iw1 originating from Triticum dicoccoides, and Iw2 from Aegilops tauschii were developed by comparative genomics analyses of Brachypodium, sorghum and rice genomic sequences corresponding to the syntenic regions of the Iw loci in wheat. Eleven Iw1 and eight Iw2 linked EST markers were developed and mapped to linkage maps on the distal regions of chromosomes 2BS and 2DS, respectively. The Iw1 locus mapped within a 0.96 cM interval flanked by the BE498358 and CA499581 EST markers that are collinear with 122 kb, 202 kb, and 466 kb genomic regions in the Brachypodium 5S chromosome, the sorghum 6S chromosome and the rice 4S chromosome, respectively. The Iw2 locus was located in a 4.1 to 5.4-cM interval in chromosome 2DS that is flanked by the CJ886319 and CJ519831 EST markers, and this region is collinear with a 2.3 cM region spanning the Iw1 locus on chromosome 2BS. Both Iw1 and Iw2 co-segregated with the BF474014 and CJ876545 EST markers, indicating they are most likely orthologs on 2BS and 2DS. These high-resolution maps can serve as a framework for chromosome landing, physical mapping and map-based cloning of the wax inhibitors in wheat

Genetic analysis of wax inhibitors <i>Iw1</i> and <i>Iw2</i> in hexaploid wheat.

<p>A, H, B represent homozygous non-glaucousness, heterozygous and homozygous glaucousness, respectively.</p

Colinearity between Brachypodium, sorghum and rice in the syntenic genomic region of wheat wax inhibitors <i>Iw1</i> and <i>Iw2.</i>

<p>Colinearity between Brachypodium, sorghum and rice in the syntenic genomic region of wheat wax inhibitors <i>Iw1</i> and <i>Iw2.</i></p

EST markers of the wax inhibitors mapped in the <i>Iw1</i> and <i>Iw2</i> genomic regions.

<p>EST markers of the wax inhibitors mapped in the <i>Iw1</i> and <i>Iw2</i> genomic regions.</p

Comparative high-resolution genetic linkage maps of the wax inhibitors <i>Iw1</i> and <i>Iw2</i> in wheat.

<p>(1a) Physical bin map of <i>Iw1</i>. <i>Iw1</i> was mapped to distal bin 2BS3-0.84-1.00. (1b) Genetic linkage map of <i>Iw1</i> on wheat chromosome 2BS with genetic distances in cM shown on the left, markers shown on the right. (1c) The orthologous genomic region of <i>Iw1</i> on <i>Brachypodium</i> chromosome 5 with putative genes on the left. (1d) The orthologous genomic region of <i>Iw1</i> on sorghum chromosome 6 with putative genes on the right. (1e) The orthologous genomic region of <i>Iw1</i> on rice chromosome 4 with putative genes on the right. (1f) Genetic linkage map of <i>Iw2</i> on wheat chromosome 2DS using the ITMI population. Genetic distances in cM are shown on the left, and markers are shown on the right. (1g) DH population genetic linkage map of <i>Iw2</i> on wheat chromosome 2DS. The markers are shown on the left, and genetic distances in cM are shown on the right. The lines and green solid boxes indicated orthologous gene pairs and the blue solid boxes indicated non-orthologous genes between wheat, <i>Brachypodium</i>, rice and sorghum.</p