DMM Model Research Articles

Echinacoside Upregulates Sirt1 to Suppress Endoplasmic Reticulum Stress and Inhibit Extracellular Matrix Degradation In Vitro and Ameliorates Osteoarthritis In Vivo.

Background Osteoarthritis (OA) is a progressive illness that destroys cartilage. Oxidative stress is a major contributor of OA, while endoplasmic reticulum (ER) stress is the key cellular damage under oxidative stress in chondrocytes. Echinacoside (ECH) is the main extract and active substance of Cistanche, with potent antioxidative stress (OS) properties, and currently under clinical trials in China. However, its function in OA is yet to be determined. Purpose We aimed to explore the specific role of ECH in the occurrence and development of OA and its underlying mechanism in vivo and in vitro. Methods After the mice were anesthetized, the bilateral medial knee joint meniscus resection was performed to establish the DMM model. TBHP was used to induce oxidative stress to establish the OA model in chondrocytes in vitro. Western blot and RT-PCR were used to evaluate the level of ER stress-related biomarkers such as p-PERK/PERK, GRP78, ATF4, p-eIF2α/eIF2α, and CHOP and apoptosis-related proteins such as BAX, Bcl-2, and cleaved caspase-3. Meanwhile, we used SO staining, immunofluorescence, and immunohistochemical staining to evaluate the pharmacological effects of ECH in mice in vivo. Results We demonstrated the effectiveness of ECH in suppressing ER stress and restoring ECM metabolism in vitro. In particular, ECH was shown to suppress tert-Butyl hydroperoxide- (TBHP-) induced OS and subsequently lower the levels of p-PERK/PERK, GRP78, ATF4, p-eIF2α/eIF2α, and CHOP in vitro. Simultaneously, ECH reduced MMP13 and ADAMTS5 levels and promoted Aggrecan and Collagen II levels, suggesting ECM degradation suppression. Moreover, we showed that ECH mediates its cellular effects via upregulation of Sirt1. Lastly, we confirmed that ECH can protect against OA in mouse OA models. Conclusion In summary, our findings indicate that ECH can inhibit ER stress and ECM degradation by upregulating Sirt1 in mouse chondrocytes treated with TBHP. It can also prevent OA development in vivo.

Experimental and Numerical Study of Behaviour of Reinforced Masonry Walls with NSM CFRP Strips Subjected to Combined Loads

Near surface mounted (NSM) carbon fibers reinforced polymer (CFRP) reinforcement is one of the techniques for reinforcing masonry structures and is considered to provide significant advantages. This paper is composed of two parts. The first part presents the experimental study of brick masonry walls reinforced with NSM CFRP strips under combined shear-compression loads. Masonry walls have been tested under vertical compression, with different bed joint orientations 90° and 45° relative to the loading direction. Different reinforcement orientations were used including vertical, horizontal, and a combination of both sides of the wall. The second part of this paper comprises a numerical analysis of unreinforced brick masonry (URM) walls using the detailed micro-modelling approach (DMM) by means of ABAQUS software. In this analysis, the non-linearity behavior of brick and mortar was simulated using the concrete damaged plasticity (CDP) constitutive laws. The results proved that the application of the NSM-CFRP strips on the masonry wall influences significantly strength, ductility, and post-peak behavior, as well as changing the failure modes. The adopted DMM model provides a good interface to predict the post peak behavior and failure mode of unreinforced brick masonry walls.

Deep learning with LSTM based distributed data mining model for energy efficient wireless sensor networks

Wireless sensor network (WSN) comprises a collection of sensor nodes employed to monitor and record the status of the physical environment and organize the gathered data at a central location. This paper presents a deep learning based distributed data mining (DDM) model to achieve energy efficiency and optimal load balancing at the fusion center of WSN. The presented DMM model includes a recurrent neural network (RNN) based long short-term memory (LSTM) called RNN-LSTM, which divides the network into various layers and place them into the sensor nodes. The proposed model reduces the overhead at the fusion center along with a reduction in the number of data transmission. The presented RNN-LSTM model is tested under a wide set of experimentation with varying number of hidden layer nodes and signaling intervals. At the same time, the amount of energy needed to transmit data by RNN-LSTM model is considerably lower than energy needed to transmit actual data. The simulation results indicated that the RNN-LSTM reduces the signaling overhead, average delay and maximizes the overall throughput compared to other methods. It is noted that under the signaling interval of 240 ms, it can be shown that the RNN-LSTM achieves a minimum average delay of 190 ms whereas the OSPF and DNN models shows average delay of 230 ms and 230 ms respectively.

The protective effect of Ellagic acid (EA) in osteoarthritis: An in vitro and in vivo study

Osteoarthritis (OA), a progressive joint disorder, is principally characterized by the degeneration and destruction of the articular cartilage. Ellagic acid (EA), a natural polyphenol found in berries and nuts has shown potent anti-inflammatory effects, however, its effects and underlying mechanisms on OA have seldom been systematically illuminated. In this study, we reported the anti-inflammatory effects of Ellagic acid (EA) in the progression of OA in both in vitro and in vivo experiments. in vitro study, IL-1β-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), Nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), and interleukin-6 (IL-6) were inhibited by Ellagic acid (EA). Moreover, Ellagic acid (EA) down-regulated the IL-1β-stimulated matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) while up-regulated the collagen of type II and aggrecan. Mechanistically, we revealed that Ellagic acid (EA) suppressed nuclear factor kappa B (NF-κB) signaling in IL-1β -induced chondrocytes. And Ellagic acid (EA)-induced protectiveness in OA development was also shown by the DMM model. Taken together, our data indicate that Ellagic acid (EA) may serve as a potential drug for OA treatment.

The protective effect of hesperetin in osteoarthritis: an in vitro and in vivo study.

Osteoarthritis (OA), a progressive joint disorder, is principally characterized by the degeneration and destruction of articular cartilage. Previous research studies demonstrated that inflammation and ECM degradation play a major role in OA development. Hesperetin, the aglycone of neohesperidin found in the peel of Citrus aurantium L. (Rutaceae), demonstrated in several studies potential anti-inflammatory activity in a variety of diseases. However, the mechanisms by which hesperetin plays a protective role in osteoarthritis (OA) are not completely understood. In this study, we found the anti-inflammatory effects of hesperetin in the progression of OA in both in vitro and in vivo experiments. In vitro, IL-1β-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2), and interleukin-6 (IL-6) were inhibited by hesperetin. Moreover, hesperetin down-regulated the IL-1β-stimulated matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) while up-regulating collagen type II and aggrecan. Mechanistically, we revealed that hesperetin suppressed nuclear factor kappa B (NF-κB) signaling by activating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in IL-1β-induced chondrocytes. Hesperetin-induced repression of OA development is shown using a DMM model. Taken together, our findings suggest that hesperetin may be a novel potential therapeutic agent for repressing the development of OA.

Downregulating Akt/NF-κB signaling and its antioxidant activity with Loureirin A for alleviating the progression of osteoarthritis: In vitro and vivo studies

Osteoarthritis(OA) is one of the most common diseases in orthopedics. It is characterized by degeneration of articular cartilage and chronic inflammation. In this study, we aim to elucidate the mechanism of Loureirin A’s therapeutic effect in OA progression. In vitro, Loureirin A pretreatment can significantly inhibit production of NO, PGE2, COX-2, TNF-α, iNOS andIL-6 induced by IL-1β in mouse articular chondrocytes. Moreover, Loureirin A suppressed the expression of matrix metalloproteinase-9(MMP-9), which leads to degradation of the extracellular matrix. The degradation of aggrecan and type II collagen protein in the extracellular matrix (ECM) stimulated by IL-1β was reversed. For signal pathway research, Loureirin A dramatically inhibited the phosphorylation of AKT and subsequent NF-κB entering into the nucleus caused by IL-1β in chondrocytes. Besides, a number of related indicators suggested that Loureirin A has a strong antioxidant activity in the treatment of osteoarthritis via increasing content of SOD2 and suppressing MDA and ROS. In addition, in vivo study demonstrated that Loureirin A could ameliorated the progression of OA in mice DMM model In conclusion, all results showed that Loureirin A may be a potential therapeutic candidate for the OA.

The N-Acetyl Phenylalanine Glucosamine Derivative Attenuates the Inflammatory/Catabolic Environment in a Chondrocyte-Synoviocyte Co-Culture System

Osteoarthritis (OA), the most prevalent degenerative joint disease, still lacks a true disease-modifying therapy. The involvement of the NF-κB pathway and its upstream activating kinases in OA pathogenesis has been recognized for many years. The ability of the N-acetyl phenylalanine glucosamine derivative (NAPA) to increase anabolism and reduce catabolism via inhibition of IKKα kinase has been previously observed in vitro and in vivo. The present study aims to confirm the chondroprotective effects of NAPA in an in vitro model of joint OA established with primary cells, respecting both the crosstalk between chondrocytes and synoviocytes and their phenotypes. This model satisfactorily reproduces some features of the previously investigated DMM model, such as the prominent induction of ADAMTS-5 upon inflammatory stimulation. Both gene and protein expression analysis indicated the ability of NAPA to counteract key cartilage catabolic enzymes (ADAMTS-5) and effectors (MCP-1). Molecular analysis showed the ability of NAPA to reduce IKKα nuclear translocation and H3Ser10 phosphorylation, thus inhibiting IKKα transactivation of NF-κB signalling, a pivotal step in the NF-κB-dependent gene expression of some of its targets. In conclusion, our data confirm that NAPA could truly act as a disease-modifying drug in OA.

Activation of Nrf2/HO-1 signal with Myricetin for attenuating ECM degradation in human chondrocytes and ameliorating the murine osteoarthritis

BackgroundOsteoarthritis (OA), one of the prevailing joint degenerative disorders, contributes to the disability around the world. However, no effective therapeutic was introduced currently. Myricetin was reported to possess the function of anti-inflammatory, anti-diabetic and anti-cancer. Thus, we investigate the protection role of myricetin in OA progression and the potential molecular mechanism in present study. MethodsQuantitative realtime PCR and western blotting were performed to evaluate the expression of MMP-13, Aggrecan, iNOS, and COX-2 at both gene and protein levels. An enzyme-linked immunosorbent assay was used to evaluate the levels of inflammatory factors (PGE2, TNF-α, and IL-6). The PI3K/AKT, Nrf2/HO-1 and nuclear factor kappa B (NF-κB) signaling pathways were analyzed by western blotting, and immunofluorescence was used to assess the expression of Nrf2, Collagen II and MMP13. The in vitro effect of myricetin was evaluated by intragastric administration into a mouse osteoarthritis model induced by destabilization of the medial meniscus. ResultsMyricetin not only inhibited the generation of inflammatory mediators and cytokines such as nitric oxide (NO), prostaglandin E2 (PGE2), TNF-α and IL-6, but also suppressed the production of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in human chondrocytes under IL-1β stimulation. Moreover, Metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS5), which resulted in the degradation of cartilage, were also suppressed in chondrocytes with the treatment of myricetin. To explore the potential mechanism, we found out that myricetin suppressed NF-κB signaling pathway through Nrf2/HO-1 axis in human chondrocytes. Besides, myricetin regulated the Nrf2 signaling pathway through PI3K/Akt pathway. In addition, in vivo study demonstrated that myricetin could ameliorated the progression of OA in mice DMM model through PI3K/Akt mediated Nrf2 signaling pathway. ConclusionTaken together, our data first demonstrated that myricetin possesses the therapeutic potential on OA through PI3K/Akt mediated Nrf2/HO-1 signaling pathway.

The progression of post-traumatic osteoarthritis in the murine DMM model is marked by distinctive epigenomic patterns associated with transcriptomic changes in articular cartilage

The progression of post-traumatic osteoarthritis in the murine DMM model is marked by distinctive epigenomic patterns associated with transcriptomic changes in articular cartilage

MicroRNA 27B-3P: role in extracellular matrix regulation in osteoarthritis synovial fibroblasts

Purpose: Synovial fibrosis is a key pathological event that contributes towards joint destruction, pain and stiffness associated with osteoarthritis (OA). Fibrosis is associated with the accumulation of excessive amount of extra-cellular matrix (ECM) resulting in tissue damage. Currently, endogenous mechanisms that play a key role in the initiation and progression of synovial fibrosis during OA are not well understood. We have previously shown that the expression of a small non-coding RNA called microRNA27b-3p (miR-27b-3p) is elevated in the synovial fluid of late-stage (Kellgren-Lawrence, KL score 3 & 4) compared to early-stage (KL score 1 & 2) radiographic knee OA patients. Furthermore, we also observed that miR-27b-3p is abundantly expressed in OA synovium (Y-H. Li, G. Tavallaee, et al. 2016). Since the role of miR-27b-3p in synovial pathology associated with OA has never been studied; we investigated if miR-27b-3p plays any role in ECM regulation in the OA synovium. Methods: Synovial tissues were obtained from OA patients undergoing total knee replacement with informed written consent. Primary OA synovial fibroblasts (major cell types present in the synovium) were isolated, cultured and transfected with miR-27b-3p mimic/inhibitor and subjected to qPCR arrays specific for ECM markers. Results obtained from arrays were further validated using quantitative-PCR analysis. For in vivo studies, mice were also subjected to DMM model of OA to determine the expression of miR-27b-3p during the time course of OA development in knee joint using in situ hybridization (ISH). Results: ECM-specific qPCR-arrays followed by validation of responsive genes by quantitative-PCR analysis revealed that miR-27b-3p mimic treatment resulted in a significant upregulation of key ECM genes including pro-collagen type-I (COL1A1), A disintegrin and metalloproteinase with thrombospondin motifs 8 (ADAMTS-8), Thrombospondin 1 (THBS1), fibronectin1 (FN1), Collagen 5 A 1 (COL5A1) and Collagen 14 A 1 (COL14A1) in OA Synovial fibroblasts. Furthermore, miR-27b-3p mimic resulted in a marked increase in type-I collagen protein expression; this effect was inhibited by miR-27b-3p inhibitor. Overall, these results suggest that miR-27b-3p may play a key role in the regulation of key ECM components in OA synovial fibroblasts. Next, we employed “Watson Discovery tool” to identify direct targets of miR-27b-3p to further elucidate its signalling pathway. This tool identified a panel of 11 genes including peroxisome proliferator-activated receptor gamma (PPARγ) as direct targets for miR-27b-3p. Indeed, we confirmed that miR-27b-3p mimic treatment results in a marked suppression of PPARγ expression, while inhibition of miR-27b-3p upregulates PPARγ, suggesting that miR-27b-3p may impart its ECM regulatory effect through modulation of PPARγ. Furthermore, ISH of DMM-induced OA mice knee joints further show that miR-27b-3p expression is prominent in the synovial lining and fibrocartilage compared to sham control mice in vivo. Conclusions: Our results thus far suggest that, in OA synovial fibroblasts, miR-27b-3p is involved in the regulation of key ECM components. Our data also suggest that miR-27b-3p may signal via negative regulation of PPARγ. Our ongoing studies are confirming if miR-27b-3p signalling via PPARγ controls ECM regulation in OA synovial fibroblasts. Our in vivo studies show that miR-27b-3p expression is elevated in the synovium during OA. To comprehensively investigate the endogenous role of miR-27b-3p in synovial pathology, we have intra-articularly injected mouse knee joints with the in-vivo grade mimic of miR-27b-3p to determine any changes in the synovium upon miR-27b-3p treatment in vivo.

Effects of Delegated Water Provisioning on Quality of Drinking Water in Low Income Areas of Kisumu County, Kenya

Only 62% of the African population have access to improved water supply. In Kenya 14% of the households in the urban areas, are privately connected to improved water supply systems. However, intermittent water supply has been reported to be a constant constraint in most low income areas in Kenya, making the residents of these areas to seek for alternative water sources such as water cart vendors, with exorbitant water prices and questionable water quality. Intermittent water supply increases the risk of water contamination through breaks and leaks leading to life threatening waterborne diseases. Delegated Management Model was adopted by water utilities in developing countries to address water access and quality issues in low income areas in developing countries. The aim of the study was to investigate the impact of DMM on the quality of drinking water in low-income areas of Kisumu County in Kenya. A descriptive cross-sectional research design was adopted. A total of 80 water samples were collected with 56 collected at the water kiosks while 24 were collected from the households. A two-sample t-test was used to determine if the differences in quality of the drinking water from the two settlements was significant at 95% confidence interval and p value set at .05. The study findings at the point of supply (water kiosks), indicated that, only the PH was within the WHO recommended standards. Turbidity, residual chlorine, total coliforms and Faecal Coliforms were all above the WHO recommended levels, and were statistically significant at p 1), total Coliforms and faecal Coliforms were all above the WHO standards. Both turbidity, total and faecal coliforms recorded significant decrease at p <0.05 though the parameters were still not within the WHO recommended levels. Though the DMM model of water supply in Nyalenda and Manyatta has improved access to water in the two informal settlement areas, findings show alterations in water quality parameters both at the water kiosks and at the household level which indicates contamination in the water supply. The study therefore recommends closer water quality monitoring at the Supply points (water kiosks) and at the households to identify and prevent sources of contamination. Further, health education strategies should be put in place to enhance proper water handling and storage among the residents. Further research should be done to identify the source of contamination. Keywords: Water, Drinking water , Water quality, Water Provisioning, low income areas DOI : 10.7176/JHMN/60-12 Publication date :March 31 st 2019

Opposite roles of pannexins in post-traumatic versus aging associated osteoarthritis

Purpose: Osteoarthritis (OA) is a highly disabling and common degenerative joint disease. OA results from pathological changes in all joint tissues during aging or following joint injury. The mechanisms driving disease progression remain unclear, thus resulting in a lack of disease modifying treatments. A hallmarking feature of OA is cartilage degeneration, and chondrocyte hypertrophy is an important driver of cartilage breakdown. Pannexin 3 (Panx3) has been identified as a novel mediator of this process, and our recent study has shown that deletion of the Panx3 gene delays surgically induced cartilage degeneration in the DMM model in mice. Panx1, another member in the pannexin family, shares 60% sequence amino acid homology with Panx3 and is found ubiquitously throughout the joint and the body. Hence, in this study, we examine the systemic effects of global Panx3 and Panx1/Panx3 deletion during aging, with a specific focus on joint and skeletal health. Methods: WT and Panx3-/- mice were aged to 18 and 24 months of age. In parallel, WT and Panx1-/-/Panx3-/- mice were also aged to 24 months of age. MicroCT analysis was used to investigate bone mineral density and body composition. Joints were harvested, and histopathological analysis of OA development was conducted. The modified OARSI scoring system was used to assess cartilage destruction during aging. OsteoMeasure software was used to analyze subchondral bone parameters including subchondral thickness and area. Synovial changes were assessed using a synovitis scoring system modified from Krenn et al. Results: Our data show that the global loss of Panx3 and Panx1/Panx3 is not associated with increased mortality or significant changes in body composition with aging. We found that bone mineral density changes associated with aging were reduced in Panx3-/- mice compared to WT, although there were no significant differences in absolute bone mineral density at 24 months. Mice lacking Panx3 and Panx1/Panx3 had shorter appendicular and axial skeletons compared to WT mice. Lastly, we showed that loss of Panx3 dramatically accelerated cartilage degeneration with aging, at both 18 and 24 months. This is in sharp contrast to the protective effect previously observed in young mice following joint surgery. At 24 months of age, mice lacking Panx1/Panx3 also showed increased cartilage degeneration compared to WT mice. Conclusions: These studies highlight a novel, OA subtype-specific role for Panx3 in the maintenance of joint health following traumatic injury and with aging. While our previous data shows loss of Panx3 protects against post-DMM OA progression, these data show that loss of Panx3 accelerates OA progression during aging. In conclusion, this study shows that Panx3 and likely Panx1 are essential for the maintenance of cartilage homeostasis in aging mice and reinforces the idea that molecular mechanisms driving post-trauamtic and primary aging associated OA are distinct.

Defining the predictive utility of the mouse DMM model of osteoarthritis for testing/developing therapeutic agents

Defining the predictive utility of the mouse DMM model of osteoarthritis for testing/developing therapeutic agents

Early Changes of Articular Cartilage and Subchondral Bone in The DMM Mouse Model of Osteoarthritis

To examine the early changes of articular cartilage and subchondral bone in the DMM mouse model of osteoarthritis, mice were subjected to DMM or SHAM surgery and sacrificed at 2-, 5- and 10-week post-surgery. Catwalk gait analyses, Micro-Computed Tomography, Toluidine Blue, Picrosirius Red and Tartrate-Resistant Acid Phosphatase (TRAP) staining were used to investigate gait patterns, joint morphology, subchondral bone, cartilage, collagen organization and osteoclasts activity, respectively. Results showed OA progressed over 10-week time-course. Gait disparity occurred only at 10-week post-surgery. Osteophyte formed at 2-week post-surgery. BMDs of DMM showed no statistical differences comparing to SHAM at 2 weeks, but BV/TV is much higher in DMM mice. Increased BMD was clearly found at 5- and 10-week post-surgery in DMM mice. TRAP staining showed increased osteoclast activity at the site of osteophyte formation of DMM joints at 5- and 10-week time points. These results showed that subchondral bone turnover might occurred earlier than 2 weeks in this mouse DMM model. Gait disparity only occurred at later stage of OA in DMM mice. Notably, patella dislocation could occur in some of the DMM mice and cause a different pattern of OA in affected knee.

Monascin inhibits IL-1β induced catabolism in mouse chondrocytes and ameliorates murine osteoarthritis.

Osteoarthritis (OA) is an age-related degenerative disease and is the fourth major cause of disability, but there are no effective therapies because of its complex pathology and the side effects of the drugs. Previous research demonstrated that inflammation and ECM degradation play major roles in OA development. Monascin is an azaphilonoid pigment extracted from Monascus-fermented rice with a potential anti-inflammatory effect reported in various preclinical studies. In the present study, we investigated the protectiveness of monascin on interleukin (IL)-1β-induced mouse chondrocytes and surgical destabilization of the medial meniscus mouse (DMM) OA models. In vitro, monascin treatment inhibited the IL-1β-induced expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). In addition, the IL-1β-stimulated matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) upregulation and type two collagen and aggrecan degradation were reversed by monascin. Mechanistically, we revealed that monascin suppressed nuclear factor kappa B (NF-κB) signalling by activating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in IL-1β-induced chondrocytes. And monascin-induced protectiveness in OA development was also shown by using a DMM model. Altogether, our results suggested that monascin could be a novel therapeutic approach for OA.

The “don't eat me” signal CD47 is a novel diagnostic biomarker and potential therapeutic target for diffuse malignant mesothelioma

ABSTRACTDiffuse malignant mesothelioma (DMM) is one of the prognostically most discouraging cancers with median survivals of only 12–22 months. Due to its insidious onset and delayed detection, DMM is often at an advanced stage at diagnosis and is considered incurable. Combined chemo- and radiotherapy followed by surgery only marginally affect outcome at the cost of significant morbidity. Because of the long time period between exposure to asbestos and disease onset, the incidence of DMM is still rising and predicted to peak around 2020. Novel markers for the reliable diagnosis of DMM in body cavity effusion specimens as well as more effective, targeted therapies are urgently needed. Here, we show that the “don't eat me” signalling molecule CD47, which inhibits phagocytosis by binding to signal regulatory protein α on macrophages, is overexpressed in DMM cells. A two-marker panel of high CD47 expression and BRCA1-associated protein 1 (BAP-1) deficiency had a sensitivity of 78% and specificity of 100% in discriminating DMM tumour cells from reactive mesothelial cells in effusions, which is superior to the currently used four-marker combination of BAP-1, glucose transporter type 1, epithelial membrane antigen and desmin. In addition, blocking CD47 inhibited growth and promoted phagocytosis of DMM cell lines by macrophages in vitro. Furthermore, DMM tumours in surgical specimens from patients as well as in a mouse DMM model expressed high levels of CD47 and were heavily infiltrated by macrophages. Our study demonstrates that CD47 is an accurate novel diagnostic DMM biomarker and that blocking CD47 may represent a promising therapeutic strategy for DMM.

Activated FGFR3 prevents subchondral bone sclerosis during the development of osteoarthritis in transgenic mice with achondroplasia.

The purpose of this study is to investigate the morphometric changes of the subchondral bone during the development of osteoarthritis (OA) in transgenic mice with achondroplasia (Fgfr3ach ) carrying a heterozygous gain-of-function mutation in Fgfr3. Two OA models (spontaneously developed with age: The aging model, and surgically induced by destabilization of the medial meniscus: The DMM model) were established. Articular cartilage, epiphysis, and metaphysis of the knee joint were histologically and morphometrically compared between wild-type mice, and Fgfr3ach mice in both OA models. Articular cartilage degeneration was scored according to the Osteoarthritis Research Society International (OARSI) scoring system. Several morphometric parameters including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular bone thickness (Tb.Th), and subchondral bone thickness in the medial tibial plateau (MTP) (Sb.Th med) were quantified by micro-computed tomography (CT). In the aging model, although there were no significant differences in the OARSI score between wild-type mice and Fgfr3ach mice, Sb.Th med and Tb.Th in the epiphysis significantly increased in wild-type mice. In the DMM model, the OARSI score of the medial compartment was significantly lower in Fgfr3ach mice than in wild-type mice. BMD, BV/TV, and Tb.Th in the epiphysis increased in wild-type mice and unchanged in Fgfr3ach mice, and the Sb.Th med was significantly larger in wild-type mice after surgery. Subchondral sclerosis, which preceded the cartilage degeneration, was inhibited in Fgfr3ach mice. Activated FGFR3 signaling prevented sclerotic changes of the subchondral bone and subsequent cartilage degeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:300-308, 2018.

Provision of digital reference services in academic libraries in Kenya: a review

Rationale - The process of locating and acquiring relevant information from libraries is getting more complicated due to the vast amount of information resources one has to plough through. To serve users purposefully, an academic library should be able to avail to users the tools and services that lessen the task of searching for information.Design - The research proposed a two-phase data mining through analysing the access behaviour of users. In the first phase, the Ant Colony Clustering Algorithm was used as the data mining method and separated users into several clusters depending on access records used. The clusters were in the form of course groupings. Users who have similar interests and behaviour were collected in the same cluster. In the second phase, the user records in the same cluster were analysed further. The second phase relied on association which was used to discover the relationship between users and information resources, users’ interests and their information access behaviour.Findings - It was ascertained that although users were able to locate and retrieve the information they needed, it was not up to the degree of satisfaction they expected. Furthermore, it took them some time to acquire the information. Using data mining together with selective dissemination of information would enable users to access relevant information without promptly thus saving time and other resources. Practical implications - The mining of user data within library databases would facilitate a better understanding of user needs and requirements leading to the development and delivery of specialised and more fulfilling services.Originality - The proposed DMM model is original as it is one of a kind that suggests integrating SDI with data mining in libraries.

A 32-mer fragment of aggrecan promotes knee hyperalgesia in the DMM model of osteoarthritis through direct nociceptor activation via TLR2

A 32-mer fragment of aggrecan promotes knee hyperalgesia in the DMM model of osteoarthritis through direct nociceptor activation via TLR2

A comprehensive simulation study of a network-based distributed mobility management framework

New mobility solutions are required for mobile environments characterised by an ever-increasing number of mobile devices and volume of internet data traffic. A single mobility anchor in the current Centralised Mobility Management CMM performs all mobility and routing functionalities. Distributed Mobility Management DMM paradigm is introduced recently to overcome scalability, reliability and non-optimal routing issues of the CMM. The DMM approach is proposed to flatten the network architecture by moving the mobility anchors closer to the users and separating the control and data planes at the network edge. In this paper, we develop and implement a network-based DMM model using NS2 simulation tool. Extensive simulations are performed to evaluate the performance of the DMM against that of the CMM. The simulation results indicate that the DMM approach outperforms the CMM approach under various mobility environments. Thus, this study verifies previous analytical studies and provides more accurate findings in DMM.