Quantitative ultrasonic assessment for detecting microscopic cartilage damage in osteoarthritis

Osteoarthritis (OA) is one of the most prevalent chronic conditions. The histological cartilage changes in OA include surface erosion and irregularities, deep fissures, and alterations in the staining of the matrix. The reversibility of these chondral alterations is still under debate. It is expected that clinical and basic science studies will provide the clinician with new scientific information about the natural history and optimal treatment of OA at an early stage. However, a reliable method for detecting microscopic changes in early OA has not yet been established. We have developed a novel system for evaluating articular cartilage, in which the acoustic properties of the articular cartilage are measured by introducing an ultrasonic probe into the knee joint under arthroscopy. The purpose of this study was to assess microscopic cartilage damage in OA by using this cartilage evaluation system on collagenase-treated articular cartilage in vivo and in vitro. Ultrasonic echoes from articular cartilage were converted into a wavelet map by wavelet transformation. On the wavelet map, the maximum magnitude and echo duration were selected as quantitative indices. Using these indices, the articular cartilage was examined to elucidate the relationships of the ultrasonic analysis with biochemical, biomechanical and histological analyses. In the in vitro study, the maximum magnitude decreased as the duration of collagenase digestion increased. Correlations were observed between the maximum magnitude and the proteoglycan content from biochemical findings, and the maximum magnitude and the aggregate modulus from biomechanical findings. From the histological findings, matrix staining of the surface layer to a depth of 500 μm was closely related to the maximum magnitude. In the in vivo study, the maximum magnitude decreased with increasing duration of the collagenase injection. There was a significant correlation between the maximum magnitude and the aggregate modulus. The evaluation system therefore successfully detected microscopic changes in degenerated cartilage with the use of collagen-induced OA

Association of serum leptin with inflammation

Background : The roles of serum leptin in knee joint inflammation are unclear. The objective of this study was to identify any associations of serum leptin level with intra-articular inflammatory cytokine levels in acute arthritic and nonarthritic knees of mice. Methods : Acute arthritis was induced by intra-articular injection of 2% carrageenan. Three groups (leptin-deficient ob/ob, wild-type (WT) and high-fat diet (HFD)-fed WT) were made. Serum leptin and inflammatory cytokines in the infrapatellar fat pad and synovium were measured before and 24 hr after injection. Affected knee joints were excised for histology 24 hr after injection. Results : The HFD-WT group had significantly higher serum leptin than the ob/ob and WT groups before and after carrageenan injection. The HFD-WT group had significantly higher IL-1β and IL-6 in the infrapatellar fat pad and synovium than ob/ob and WT before injection but significantly lower IL-1β, IL-6 and TNF-α than the ob/ob group at 24 hr. Conclusions : Hyperleptinemia induced by a HFD is involved in low-grade intra-articular inflammation in nonarthritic knee joints. In contrast, leptin deficiency causes excessive intra-articular inflammation in carrageenan-induced acute arthritis. Leptin alleviates acute arthritis, while chronic hyperleptinemia is involved in low-grade inflammation in normal knee joints

神経系小胞体ストレスと誘導型アポトーシスのニコチンとニューロトロフィンによる防御機構

Neuronal degenerative diseases including Alzheimer\u27s, Parkinson\u27s and polyglutamine diseases are considered to involve endoplasmic reticulum (ER) stress, which leads to ER stress-mediated apoptosis of some neurons. In the process of these diseases, it has been reported that unfolded proteins are accumulated in the ER and this step is critical for progression of neuronal apoptosis through the caspase cascade involving an ER stress-specific caspase, caspase-12. During ER stress, chaperone proteins including glucose-regulated protein 78 (GRP78) are expressed to fold these unfolded proteins as an unfolded protein response (UPR). In cultured cells, ER stress can be induced by tunicamycin (Tm) or thapsigargin (Tg). We report that nerve growth factor (NGF), a well-known member of the neurotrophin family, suppressed Tm-, Tg- and 2-deoxy-glucose (2DG)-induced ER stress-mediated apoptosis in PC12 cells as a model neuron. NGF prevented the progression of ER stress-induced apoptosis by the suppression of activation of caspase-12 via the PI3-kinase-Akt signaling pathway. NGF up-regulated the ER stress-stimulated expression of GRP78, but this up-regulation of GRP78 by NGF did not contribute to the protective effect ofNGF on ER stress-induced apoptosis. We found that nicotine protected against Tm-induced ER stress-mediated apoptosis but not Tg-induced ER stress-mediated apoptosis in PC12 cells. We also found that the expression of GRP78 was suppressed by nicotine in Tm-treated PC12 cells. Interestingly, the expression of GRP78 was not changed by nicotine in Tg-treated cells. Moreover, nicotine reduced the activation of caspase-12 in Tm-treated cells, but not in Tg-treated cells. These results suggest that nicotine prevents Tm-induced ER stress-mediated apoptosis by attenuating Tm-induced ER stress itself, probably by the clearance of accumulated unfolded proteins from the ER.This work was supported in part by grants-in-aid for scientific research from MEXT, HAITEKU (2002-2006) from MEXT and a research grant from the Smoking Research Foundation

神経変性疾患でみられる小胞体ストレス誘導型アポトーシスと神経栄養因子によるその防御機構

近年、アルツハイマー病やパーキソン病などの神経変性疾患の発症に関わる原因遺伝子の同定が急速に進行し、病態発症の詳細な分子機構の解析が行われている。そのような遺伝的要因の解析の他に、環境的要因における細胞恒常性コントロール機能の破綻機構の解析も分子レベルで行われている。それらの解析の結果、神経細胞内の小胞体内腔に、異常構造タンパク質が蓄積し、小胞体ストレスが負荷されていることによって神経変性疾患が発症することが明らかになった。また、神経変性疾患において、神経細胞は、アポトー シスによって死滅 していることも分かった。しかし、小胞体ストレス負荷からアポトーシスに至るまでの分子機構については、不明な点が多く残されている。我々は、モデル神経細胞であるPC12細胞と大脳皮質神経細胞を用いて、神経栄養因子(NGFやBDNF)が、小胞体ストレス誘導型アポトーシスを抑制することを見出した。今回、NGFやBDNFがどのように小胞体ストレス誘導型アポトーシスを抑制するのかを、細胞内分子機構を基盤として述べる。第9回関西大学先端科学技術シンポシウム(2005)「生命情報伝達系の機能分子と応答制御を基盤とするシステム開発プロジェクト」研究代表者 池内俊彦平成14年度関西大学重点領域研究助成金、文部科学省 ・日本学術捩興会科学研究費補助金、日本科学協会・笹川科学研究助成金、喫煙財団研究助成

Endoplasmic reticulum stress-induced apoptosis and its preventive mechanism: Possible therapeutic strategy against neurodegenerative disorders

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Data Integration and Analysis System (DIAS) as a Platform for Data and Model Integration: Cases in the Field of Water Resources Management and Disaster Risk Reduction

The development of data and model integration platforms has furthered scientific inquiry and helped to solve pressing social and environmental problems. While several e-infrastructure platforms have been developed, the concept of data and model integration remains obscure, and these platforms have produced few firm results. This article investigates data and model integration on the Data Integration and Analysis System (DIAS) platform, using three case projects from water-related fields. We provide concrete examples of data and model integration by analyzing the data transfer and analysis process, and demonstrate what platform functions are needed to promote the advantages of data and model integration. In addition, we introduce the Digital Object Identifier (DOI), a valuable tool for promoting data and model integration and open science. Our investigation reveals that DIAS advances data and model integration in five main ways: it is a “sophisticated and robust integration platform”; has “rich APIs, including a metadata management system, for high-quality data archive and utilization”; functions as a “core hydrological model”; and promotes a “collaborative R&D community” and “open science and data repositories”. This article will appeal especially to researchers interested in new methods of analysis, and information technology experts responsible for developing e-infrastructure systems to support environmental and scientific research