Abstract:
:A hallmark of rheumatoid arthritis is the formation of an aggressive, tumor-like structure called pannus that erodes the joint. A major cellular component of the pannus is the fibroblast-like synoviocyte (FLS), whose morphology strikingly resembles that of a transformed cell, but underlying mechanisms of this "transformation" are not known. Here, using animal models of rheumatoid arthritis, we show that arthritic FLS contain a substantial (>30%) fraction of bone marrow-derived precursors that can differentiate in vitro into various mesenchymal cell types, but inflammation prevents the multilineage differentiation. We show that the transcription factor NF-kappaB plays the key role in the repression of osteogenic and adipogenic differentiation of arthritic FLS. Furthermore, we show that specific activation of NF-kappaB profoundly enhances proliferation, motility, and matrix-degrading activity of FLS. We thus propose that arthritic FLS are mesenchymal stem cells whose differentiation is arrested at early stages of differentiation by activation of NF-kappaB.
journal_name
Proc Natl Acad Sci U S Aauthors
Li X,Makarov SSdoi
10.1073/pnas.0607939103subject
Has Abstractpub_date
2006-11-14 00:00:00pages
17432-7issue
46eissn
0027-8424issn
1091-6490pii
0607939103journal_volume
103pub_type
杂志文章abstract::Among yeasts that underwent whole-genome duplication (WGD), Kluyveromyces polysporus represents the lineage most distant from Saccharomyces cerevisiae. By sequencing the K. polysporus genome and comparing it with the S. cerevisiae genome using a likelihood model of gene loss, we show that these species diverged very s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0608218104
更新日期:2007-05-15 00:00:00
abstract::We have cloned a member of the nuclear receptor superfamily. The cDNA was isolated from a rat liver library and encodes a protein of 446 aa with a predicted mass of 50 kDa. This clone (OR-1) shows no striking homology to any known member of the steroid/thyroid hormone receptor superfamily. The most related receptor is...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.6.2096
更新日期:1995-03-14 00:00:00
abstract::There are certain genes on the sex chromosome of Drosophila for which the female contains twice as many copies as the male. Some of the genes in this group produce the same phenotype in each sex despite the dosage difference and are said, therefore, to manifest dosage compensation. The structural genes for glucose-6-p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.62.2.528
更新日期:1969-02-01 00:00:00
abstract::The major obstacle to the study of functional/structural interrelationships of spinach chloroplasts by using spin labels has been the rapid loss of the electron paramagnetic resonance (EPR) signals upon illumination with visible light. The present study demonstrates that the addition of ferredoxin and NADP+ in the pre...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.8.3107
更新日期:1975-08-01 00:00:00
abstract::High-resolution examination of pulse sequences generated by single visual cortex cells of the rhesus monkey in response to precisely controlled visual stimuli has disclosed (i) that the outputs of such neurons contain highly improbable (P less than 10(-7) numbers of identical triplets of precisely repeating pulse patt...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.24.9812
更新日期:1986-12-01 00:00:00
abstract::The mammalian target of rapamycin (mTOR) is a central regulator of cell growth and proliferation in response to growth factor and nutrient signaling. Consequently, this kinase is implicated in metabolic diseases including cancer and diabetes, so there is great interest in understanding the complete spectrum of mTOR-re...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1103746108
更新日期:2011-09-13 00:00:00
abstract::Exposure to 3TC of HIV-1 mutant strains containing non-nucleoside reverse transcriptase inhibitor (NNRTI)-specific mutations in their reverse transcriptase (RT) easily selected for double-mutant viruses that had acquired the characteristic 184-Ile mutation in their RT in addition to the NNRTI-specific mutations. Conve...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.23.13152
更新日期:1996-11-12 00:00:00
abstract::The dilute (d) coat color mutation on chromosome 9 is closely associated with an ecotropic murine leukemia virus (MuLV) genome [Jenkins, N.A., Copeland, N.G., Taylor, B.A. & Lee, B.K. (1981) Nature 293, 370-374]. DBA/2J mice homozygous for the reverse mutation to wild type at the dilute locus (d+2J) lack ecotropic vir...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.1.247
更新日期:1983-01-01 00:00:00
abstract::A parathyroid hormone-like peptide (PTH-LP) has recently been identified in human tumors associated with the syndrome of humoral hypercalcemia of malignancy. The peptide appears to be encoded by a single-copy gene that gives rise to multiple mRNAs that are heterogeneous at both their 5' and their 3' ends. Alternative ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.7.2408
更新日期:1989-04-01 00:00:00
abstract::Metallothioneins are small cysteine-rich proteins capable of binding heavy metal ions such as Zn2+ and Cd2+. They are ubiquitous tissue components in higher organisms, which tentatively have been attributed both unspecific protective functions against toxic metal ions and highly specific roles in fundamental zinc-regu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.21.10124
更新日期:1992-11-01 00:00:00
abstract::Plant morphogenesis requires coordinated cytoplasmic growth, oriented cell wall extension, and cell cycle progression, but it is debated which of these processes are primary drivers for tissue growth and directly targeted by developmental genes. Here, we used ChIP high-throughput sequencing combined with transcriptome...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1320457111
更新日期:2014-02-18 00:00:00
abstract::Despite the success statistical physics has enjoyed at predicting the properties of materials for given parameters, the inverse problem, identifying which material parameters produce given, desired properties, is only beginning to be addressed. Recently, several methods have emerged across disciplines that draw upon o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1509316112
更新日期:2016-01-05 00:00:00
abstract::As a direct simulation of a multistep proton transfer reaction involving protein residues, the proton relay shuttle between A and I forms of green fluorescent protein (GFP) is simulated in atomic detail by using a special molecular dynamics simulation technique. Electronic excitation of neutral chromophore in wild-typ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.052520799
更新日期:2002-03-05 00:00:00
abstract::Although the unifying hallmark of prion diseases is CNS neurodegeneration caused by conformational corruption of host prion protein (PrP) to its infective counterpart, contagious transmission of chronic wasting disease (CWD) results from shedding of prions produced at high titers in the periphery of diseased cervids. ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1903947116
更新日期:2019-06-18 00:00:00
abstract::Asymmetric epoxidation of various styrenes using carbocyclic oxazolidinone-containing ketone 3 has been investigated. High enantioselectivity (89-93% enantiomeric excess) has been attained for this challenging class of alkenes. Mechanistic studies show that substituents on the ketone catalyst can have electronic influ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0307548101
更新日期:2004-04-20 00:00:00
abstract::A general approach to high-throughput screening of enantiomeric excess (ee) and concentration was developed by using indicator displacement assays (IDAs), and the protocol was then applied to the vicinal diol hydrobenzoin. The method involves the sequential utilization of what we define herein as screening, training, ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0809530106
更新日期:2009-06-30 00:00:00
abstract::Adult workers in honeybee (Apis mellifera) colonies exhibit plasticity in hormonally regulated, age-based division of labor by altering their pattern of behavioral development in response to changes in colony conditions. One form of this plasticity is precocious development: levels of juvenile hormone increase prematu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.24.11726
更新日期:1992-12-15 00:00:00
abstract::African trypanosomes are protected by a densely packed surface monolayer of variant surface glycoprotein (VSG). A haptoglobin-hemoglobin receptor (HpHbR) within this VSG coat mediates heme acquisition. HpHbR is also exploited by the human host to mediate endocytosis of trypanolytic factor (TLF)1 from serum, contributi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1214943110
更新日期:2013-01-29 00:00:00
abstract::Recently, tRNA aminoacyl-tRNA synthetase pairs have been evolved that allow one to genetically encode a large array of unnatural amino acids in both prokaryotic and eukaryotic organisms. We have determined the crystal structures of two substrate-bound Methanococcus jannaschii tyrosyl aminoacyl-tRNA synthetases that ch...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0601756103
更新日期:2006-04-25 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0504744102
更新日期:2005-08-02 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.182430599
更新日期:2002-09-17 00:00:00
abstract::Osteogenin was recently purified and the amino acid sequences of tryptic peptides were determined. Osteogenin in conjunction with insoluble collagenous bone matrix induces cartilage and bone formation in vivo. To understand the mechanism of action of osteogenin, we examined its influence on periosteal cells, osteoblas...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.22.8793
更新日期:1989-11-01 00:00:00
abstract::Insight regarding how diverse enzymatic functions and reactions have evolved from ancestral scaffolds is fundamental to understanding chemical and evolutionary biology, and for the exploitation of enzymes for biotechnology. We undertook an extensive computational analysis using a unique and comprehensive combination o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1706849114
更新日期:2017-11-07 00:00:00
abstract::The spatial structure of genetic diversity underlying social variation is a critical determinant of how cooperation and conflict evolve. Here we investigated whether natural social groups of the cooperative soil bacterium Myxococcus xanthus harbor internal genetic and phenotypic variation and thus the potential for so...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1100307108
更新日期:2011-06-28 00:00:00
abstract::Continuous intravenous infusion of heparin suppresses smooth muscle cell proliferation in rats after endothelial injury but may lead to hemorrhage and other complications. The anticoagulant property has been removed from chemically modified heparin without loss of antiproliferative effect but use of such compounds is ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.10.3773
更新日期:1990-05-01 00:00:00
abstract::Most proteins are in equilibrium with partially and globally unfolded conformations. In contrast, kinetically stable proteins (KSPs) are trapped by an energy barrier in a specific state, unable to transiently sample other conformations. Among many potential roles, it appears that kinetic stability (KS) is a feature us...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0705417104
更新日期:2007-10-30 00:00:00
abstract::Incubation of sickle cells with cystamine, a thiol reagnet, resulted in the formation of an intracellular S-ethylamine derivative. The rate of the reaction was dependent upon the cystamine concentration, the temperature, and the duration of the incubation. The cystamine-treated cells demonstrated a marked inhibition o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.9.3288
更新日期:1976-09-01 00:00:00
abstract::The chemical speciation of arsenic in sediments and porewaters of aquifers is the critical factor that determines whether dissolved arsenic accumulates to potentially toxic levels. Sequestration of arsenic in solid phases, which may occur by adsorption or precipitation processes, controls dissolved concentrations. We ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0402775101
更新日期:2004-09-21 00:00:00
abstract::The active form of vitamin D, 1alpha,25-dihydroxyvitamin D [1alpha,25(OH)2D], is synthesized from its precursor 25 hydroxyvitamin D [25(OH)D] via the catalytic action of the 25(OH)D-1alpha-hydroxylase [1alpha(OH)ase] enzyme. Many roles in cell growth and differentiation have been attributed to 1,25(OH)2D, including a ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.131029498
更新日期:2001-06-19 00:00:00
abstract::We present a synthesis theorem for a family of locally equivalent measures defined on a ring of sets. This theorem is then used to exhibit a control measure for weakly compact sets of unbounded measures. In addition, the existence of a local control measure for locally strongly bounded vector measures is proved by mea...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.69.5.1083
更新日期:1972-05-01 00:00:00