Periodontal disease (PD), as an age-related disease, prevalent in middle-aged and elderly population, is characterized as inflammatory periodontal tissue loss, including gingival inflammation and alveolar bone resorption. However, the definite mechanism of aging-related inflammation in PD pathology needs further investigation. Our study is aimed at exploring the effect of inflamm-aging-related cytokines of interleukin-17 (IL-17) and interferon-γ (IFN-γ) on osteoclastogenesis in vitro and periodontal destruction in vivo. For receptor activator of nuclear factor-κB ligand- (RANKL-) primed bone marrow macrophages (BMMs), IL-17 and IFN-γ enhanced osteoclastogenesis, with the expression of osteoclastogenic mRNA (TRAP, c-Fos, MMP-9, Ctsk, and NFATc1) and protein (c-Fos and MMP-9) upregulated. Ligament-induced rat models were established to investigate the role of IL-17 and IFN-γ on experimental periodontitis. Both IL-17 and IFN-γ could enhance the local inflammation in gingival tissues. Although there might be an antagonistic interaction between IL-17 and IFN-γ, IL-17 and IFN-γ could facilitate alveolar bone loss and osteoclast differentiation.

Emerging studies have explained the crucial role of non-coding RNA (lncRNA) in various pathological progressions. The study was designed to examine the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and miRNA-124 in the differentiation of osteoclasts, to provide new clues or evidences for the pathogenesis of periodontitis. Methods: We constructed an osteoblast-osteoclast Transwell co-culture system and osteoblast-derived exosomes (OB-exo) intervention model. We assessed the osteoclastogenesis as well as the level of lncRNA-MALAT1 and miRNA-124. The mechanism for lncRNA MALAT1 targeting miR-124 modulating the differentiation of osteoclasts was investigated by cell transfection, quantitative real-time reverse transcription PCR (RT-qPCR), Western blot, and Dual-Luciferase reporter assays. Results: Osteoblast-derived exosomes were isolated and identified. Co-culture and OB-exo intervention can promote osteoclastogenesis, also significantly up-regulate the expression of MALAT1, while the level of miR-124 is the opposite. Transfection of cells with small interfering RNA (si-MALAT1) and miR-124 mimic decreased the formation of TRAP + osteoclasts and inhibited the expression of NFATc1. However, the effect was reversed when transfected with miR-124 inhibitor and si-MALAT1. The Dual-Luciferase reporter assay confirmed the binding sites between MALAT1 and miR-124, and miR-124 and NFATc1. Conclusion: LncRNA MALAT1 functioned as an endogenous sponge by competing for miR-124 binding to regulate NFATc1 expression, accelerating the progression of osteoclastogenesis.

Computer systems today are movi ng toward s both gre ater distribution and conso/idarion, ranging from multi core systems to clouds. For example, in a multicore syste m, tasks are di stributed and exec uted by multiple concurrent threads, and meanwhile the threads are consolidated to run on the system. As another example, in Amazon EC2 service which provides its computing resource to clients in terms of virtual machine instance. clients• tasks are distributed and executed in thousand s of virtual machines, and meanwhil e th e virtual machines run on a set of physical machines, leading to consolidation of the virtual machines. The systems consolidating threads contain a number of limited resources (e. g. cache, memory) to make their hosted threads run , and therefore th eir resource should be shared among these threads. Properl y allocating the shared resource among threads is crucial to achieve high overall performance. A reali stic method to all ocate resource effecti vely is to use utility function to track each thread 's resource demand and direct the resource allocation, where utility function describes each thread 's performance based on the amount of resource it gets. In the thesis, we study how to allocate a shared reso urce in the emerging computer systems, such as multicore systems, virtual machine systems to achi eve high overall perform a nce. In addition, there are a number of di stributed re source in di stributed syste ms. For example, in a web hosting center. a number of web service threads run on multiple serve rs and compete for re sources such as proce ss ing or memory. We also inws ti gated distributed resource all ocati on problem. In the thesis, we proposed efficient and effective res ource allocation algorithms. guaran teeing good pe rformance bounds. (i) We first studied how to all ocate a re source among multiple threads to minimize makcpsan. which measures the amount of tim e needed to complete a set of tas ks. We assume that a thread 's performance increases with its reso urce allocation, and th at the performance function is concave. Our fir st contribution is to give a mathematical characterization of the propertie s satisfied by an optimal resource allocation. Second. we present an algorithm th at finds a 1 + E approximatio n to th e optimal allocati on in O (nlog ?.!.J og. !.. !. .) tim e, where n is the num ber of tasks and J7 is a \'alue that f "-rp depends on the optimal solution. Simulations show that our algorithm achi eves better makespan compared to several allocation sc he mes used in practi ce or proposed in the literature.

Background: In chronic periodontitis, exosomes transport various informative substances between osteoclasts and osteoblasts in alveolar bone. Herein, we aimed to investigate the effect of exosomal micro-ribonucleic acid (miRNA/miR)-5134-5p derived from osteoclasts on osteoblastic proliferation and differentiation and the development of periodontitis in vivo and in vitro. Methods:The effects of OC-Exos on the proliferation and differentiation of osteoblasts were identified by Real-time quantitative reverse polymerase chain reaction (qRT-PCR), Western blot(WB), alkaline phosphatase(ALP) staining, etc. Exosomal miRNA expression was analyzed by sequencing. The sites of miRNA action were predicted through TargetScan and tested by double luciferase assay. After transfecting miR-5134-5p mimic/inhibitor into osteoblasts, we measured the proliferation and differentiation of osteoblasts by ALP staining and WB, etc. Furthermore, OC-Exos were injected into the gingival sulcus at the ligation site. Inflammation was observed by Hematoxylin-eosin (H&E) staining, the expression of inflammatory factors were detected by qRT-PCR, the resorption of alveolar bone was observed by Micro CT. Results: Osteoblastic proliferation and differentiation were negatively regulated by OC-Exos in vitro. miRNA sequencing analysis revealed that miR-5134-5p expression was significantly elevated in OC-Exos, which also increased in osteoblasts following OC-Exo intervention. The dual-luciferase assay revealed that miR-5134-5p and Janus kinase 2 (JAK2) had binding sites. miR-5134-5p-mimics could upregulate miR-5134-5p expression in osteoblasts while downregulating Runt-related transcription factor 2(Runx2), phosphorylated-JAK2 (p-JAK2), and phosphorylated-signal transducer and activator of transcription 3 (p-STAT3) expression and inhibited osteogenic differentiation. However, miR-5134-5p-inhibitor had the opposite effect. In vivo, the OC-Exo group demonstrated morphological disruption of periodontal tissue, massive inflammatory cell infiltration, upregulation of inflammatory factors mRNA expression, a significant decrease in BV/TV, and an increase in the cementoenamel junction and alveolar bone crest distance. Conclusion: Osteoclast-derived exosomal miR-5134-5p inhibits osteoblastic proliferation and differentiation via the JAK2/STAT3 pathway. OC-Exos exacerbate periodontal tissue inflammation and accelerate alveolar bone resorption in mice with experimental periodontitis.

No abstract