Augmented Fibroblast Growth Factor-23 Secretion in Bone Locally Contributes to Impaired Bone Mineralization in Chronic Kidney Disease in Mice.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic disorder of mineral and bone metabolism caused by CKD. Impaired bone mineralization together with increased bony secretion of fibroblast growth factor-23 (FGF23) are hallmarks of CKD-MBD. We recently showed that FGF23 suppresses the expression of tissue nonspecific alkaline phosphatase (TNAP) in bone cells by a Klotho-independent, FGF receptor-3-mediated signaling axis, leading to the accumulation of the mineralization inhibitor pyrophosphate. Therefore, we hypothesized that excessive FGF23 secretion may locally impair bone mineralization in CKD-MBD. To test this hypothesis, we induced CKD by 5/6 nephrectomy in 3-month-old wild-type (WT) mice and Fgf23-/-/VDRΔ/Δ (Fgf23/VDR) compound mutant mice maintained on a diet enriched with calcium, phosphate, and lactose. Eight weeks postsurgery, WT CKD mice were characterized by reduced bone mineral density at the axial and appendicular skeleton, hyperphosphatemia, secondary hyperparathyroidism, increased serum intact Fgf23, and impaired bone mineralization as evidenced by bone histomorphometry. Laser capture microdissection in bone cryosections showed that both osteoblasts and osteocytes contributed to the CKD-induced increase in Fgf23 mRNA abundance. In line with our hypothesis, osteoblastic and osteocytic activity of alkaline phosphatase was reduced, and bone pyrophosphate concentration was ~2.5-fold higher in CKD mice, relative to Sham controls. In Fgf23/VDR compound mice lacking Fgf23, 5/6-Nx induced secondary hyperparathyroidism and bone loss. However, 5/6-Nx failed to suppress TNAP activity, and bone pyrophosphate concentrations remained unchanged in Fgf23/VDR CKD mice. Collectively, our data suggest that elevated Fgf23 production in bone contributes to the mineralization defect in CKD-MBD by auto-/paracrine suppression of TNAP and subsequent accumulation of pyrophosphate in bone. Hence, our study has identified a novel mechanism involved in the pathogenesis of CKD-MBD.

A New Approach to Modify Plant Microbiomes and Traits by Introducing Beneficial Bacteria at Flowering into Progeny Seeds.

The microbial component of healthy seeds - the seed microbiome - appears to be inherited between plant generations and can dynamically influence germination, plant performance, and survival. As such, methods to optimize the seed microbiomes of major crops could have far-reaching implications for plant breeding and crop improvement to enhance agricultural food, feed, and fiber production. Here, we describe a new approach to modulate seed microbiomes of elite crop seed embryos and concomitantly design the traits to be mediated by seed microbiomes. Specifically, we discovered that by introducing the endophyte Paraburkholderia phytofirmans PsJN to the flowers of parent plants we could drive its inclusion in progeny seed microbiomes, thereby inducing vertical inheritance to the offspring generation. We demonstrated the introduction of PsJN to seeds of monocot and dicot plant species and the consequential modifications to seed microbiome composition and growth traits in wheat, illustrating the potential role of novel seed-based microbiomes in determining plant traits.

Comparative genome analysis of Burkholderia phytofirmans PsJN reveals a wide spectrum of endophytic lifestyles based on interaction strategies with host plants.

Burkholderia phytofirmans PsJN is a naturally occurring plant-associated bacterial endophyte that effectively colonizes a wide range of plants and stimulates their growth and vitality. Here we analyze whole genomes, of PsJN and of eight other endophytic bacteria. This study illustrates that a wide spectrum of endophytic life styles exists. Although we postulate the existence of typical endophytic traits, no unique gene cluster could be exclusively linked to the endophytic lifestyle. Furthermore, our study revealed a high genetic diversity among bacterial endophytes as reflected in their genotypic and phenotypic features. B. phytofirmans PsJN is in many aspects outstanding among the selected endophytes. It has the biggest genome consisting of two chromosomes and one plasmid, well-equipped with genes for the degradation of complex organic compounds and detoxification, e.g., 24 glutathione-S-transferase (GST) genes. Furthermore, strain PsJN has a high number of cell surface signaling and secretion systems and harbors the 3-OH-PAME quorum-sensing system that coordinates the switch of free-living to the symbiotic lifestyle in the plant-pathogen R. solanacearum. The ability of B. phytofirmans PsJN to successfully colonize such a wide variety of plant species might be based on its large genome harboring a broad range of physiological functions.