ADAR1 ablation decreases bone mass by impairing osteoblast function in mice

Bone mass is controlled through a delicate balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. We show here that RNA editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) is critical for proper control of bone mass. Postnatal conditional knockout of Adar1 (the gene encoding ADAR1) resulted in a severe osteopenic phenotype. Ablation of the Adar1 gene significantly suppressed osteoblast differentiation without affecting osteoclast differentiation in bone. In vitro deletion of the Adar1 gene decreased expression of osteoblast-specific osteocalcin and bone sialoprotein genes, alkaline phosphatase activity, and mineralization, suggesting a direct intrinsic role of ADAR1 in osteoblasts. ADAR1 regulates osteoblast differentiation by, at least in part, modulation of osterix expression, which is essential for bone formation. Further, ablation of the Adar1 gene decreased the proliferation and survival of bone marrow stromal cells and inhibited the differentiation of mesenchymal stem cells towards osteoblast lineage. Finally, shRNA knockdown of the Adar1 gene in MC-4 pre-osteoblasts reduced cyclin D1 and cyclin A1 expression and cell growth. Our results identify ADAR1 as a new key regulator of bone mass and suggest that ADAR1 functions in this process mainly through modulation of the intrinsic properties of osteoblasts (i.e., proliferation, survival and differentiation).     

A current review of molecular mechanisms regarding osteoarthritis and pain

Osteoarthritis afflicts millions of individuals across the world resulting in impaired quality of life and increased health costs. To understand this disease, physicians have been studying risk factors, such as genetic predisposition, aging, obesity, and joint malalignment; however have been unable to conclusively determine the direct etiology. Current treatment options are short-term or ineffective and fail to address pathophysiological and biochemical mechanisms involved with cartilage degeneration and the induction of pain in arthritic joints. OA pain involves a complex integration of sensory, affective, and cognitive processes that integrate a variety of abnormal cellular mechanisms at both peripheral and central (spinal and supraspinal) levels of the nervous system Through studies examined by investigators, the role of growth factors and cytokines has increasingly become more relevant in examining their effects on articular cartilage homeostasis and the development of osteoarthritis and osteoarthritis-associated pain. Catabolic factors involved in both cartilage degradation in vitro and nociceptive stimulation include IL-1, IL-6, TNF-α, PGE2, FGF-2 and PKCδ, and pharmacologic inhibitors to these mediators, as well as compounds such as RSV and LfcinB, may potentially be used as biological treatments in the future. This review explores several biochemical mediators involved in OA and pain, and provides a framework for the understanding of potential biologic therapies in the treatment of degenerative joint disease in the future.     

Biotic elicitation of ginsenoside metabolism of mutant adventitious root culture in Panax ginseng

Applied Microbiology and Biotechnology - Biotic elicitation is an important biotechnological strategy for triggering the accumulation of secondary metabolites in adventitious root cultures. These...     

<Emphasis Type="Italic">Lysobacter spongiae</Emphasis> sp. nov., isolated from spongin

A Gram-negative, motile, aerobic and rod-shaped bacterial strain designated 119BY6-57^T was isolated from spongin. The taxonomic position of the novel isolate was confirmed using the polyphasic approach. Strain 119BY6-57^T grew well at 25–30°C on marine agar. On the basis of 16S rRNA gene sequence similarity, strain 119BY6-57^T belongs to the family Xanthomonadaceae and is related to Lysobacter aestuarii S2-C^T (99.8% sequence similarity), L. maris KMU-14^T (97.5%), and L. daejeonensis GH1-9^T (97.3%). Lower sequence similarities (97.0%) were found with all of the other recognized members of the genus Lysobacter. The G + C content of the genomic DNA was 69.9 mol%. The major respiratory quinone was Q-8 and the major fatty acids were C_16:0 iso, C_15:0 iso, summed feature 9 (comprising C_17:1 iso ω9c and/or C_16:0 10-methyl), summed feature 3 (comprising C_16:1ω7c and/or C_16:1ω6c), and C_11:0 iso 3-OH. The polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, three unidentified phospholipids, and an unidentified polar lipid. DNADNA relatedness values between strain 119BY6-57^T and its closest phylogenetically neighbors were below 48.0 ± 2.1%. Based on genotypic and phenotypic characteristics, it is concluded that strain 119BY6-57^T is a new member within the genus Lysobacter, for which the name Lysobacter spongiae sp. nov. is proposed. The type strain is 119BY6-57^T (= KACC 19276^T = LMG 30077^T).     

<Emphasis Type="Italic">Baekduia soli</Emphasis> gen. nov., sp. nov., a novel bacterium isolated from the soil of Baekdu Mountain and proposal of a novel family name, <Emphasis Type="Italic">Baekduiaceae</Emphasis> fam. nov.

A taxonomic study was conducted on BR7-21^T, a bacterial strain isolated from the soil of a ginseng field in Baekdu Mountain. Comparative studies of the 16S rRNA gene sequence showed that the isolate was most closely related to Conexibacter woesei DSM 14684^T, Solirubrobacter pauli ATCC BAA-492^T, Patulibacter minatonensis JCM 12834^T, with 93.8%, 92.4%, and 91.5% sequence similarity, respectively; each genus represented a family in the order Solirubrobacterales. Strain BR7-21^T was Gram-reaction positive, non-spore forming, aerobic, non-motile, and short rod-shaped. It grew well on half-strength R2A medium. The G + C content of the genomic DNA was 73.9%. It contained meso-diaminopimelic acid in the cell wall and the major menaquinones were MK-7(H₄) and MK-8(H₄). The major fatty acids were summarized as (C_16:1ω7c/iso-C_15:0 2-OH), iso-C_16:0, and C_17:0 cyclo. On the basis of polyphasic evidence, it was proposed that strain BR7-21^T should be placed in a new genus and species, for which the name Baekduia soli gen. nov., sp. nov. was proposed with the type strain BR7-21^T (= KCTC 22257T = LMG 24797^T). The family Baekduiaceae fam. nov. is proposed to encompass the genus Baekduia gen. nov.     

SIRT3 deregulation is linked to mitochondrial dysfunction in Alzheimer's disease

Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Despite decades of study, effective treatments for AD are lacking. Mitochondrial dysfunction has been closely linked to the pathogenesis of AD, but the relationship between mitochondrial pathology and neuronal damage is poorly understood. Sirtuins (SIRT, silent mating type information regulation 2 homolog in yeast) are NAD‐dependent histone deacetylases involved in aging and longevity. The objective of this study was to investigate the relationship between SIRT3 and mitochondrial function and neuronal activity in AD. SIRT3 mRNA and protein levels were significantly decreased in AD cerebral cortex, and Ac‐p53 K320 was significantly increased in AD mitochondria. SIRT3 prevented p53‐induced mitochondrial dysfunction and neuronal damage in a deacetylase activity‐dependent manner. Notably, mitochondrially targeted p53 (mito‐p53) directly reduced mitochondria DNA‐encoded ND2 and ND4 gene expression resulting in increased reactive oxygen species (ROS) and reduced mitochondrial oxygen consumption. ND2 and ND4 gene expressions were significantly decreased in patients with AD. p53‐ChIP analysis verified the presence of p53‐binding elements in the human mitochondrial genome and increased p53 occupancy of mitochondrial DNA in AD. SIRT3 overexpression restored the expression of ND2 and ND4 and improved mitochondrial oxygen consumption by repressing mito‐p53 activity. Our results indicate that SIRT3 dysfunction leads to p53‐mediated mitochondrial and neuronal damage in AD. Therapeutic modulation of SIRT3 activity may ameliorate mitochondrial pathology and neurodegeneration in AD.     

Crystal Structures of Human Orexin 2 Receptor Bound to the Subtype-Selective Antagonist EMPA

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