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Xiaohong Yang Dian Teguh Jian-Ping Wu Bo He Thomas Brett Kirk Shengnan Qin Siming Li Honghui Chen Wei Xue Benjamin Ng Shek Man Chim Jennifer Tickner Jiake Xu 《Arthritis research & therapy》2015,17(1)
IntroductionStructural alterations in intra-articular and subchondral compartments are hallmarks of osteoarthritis, a degenerative disease that causes pain and disability in the aging population. Protein kinase C delta (PKC-δ) plays versatile functions in cell growth and differentiation, but its role in the articular cartilage and subchondral bone is not known.MethodsHistological analysis including alcian blue, safranin O staining and fluorochrome labeling were used to reveal structural alterations at the articular cartilage surface and bone–cartilage interface in PKC-δ knockout (KO) mice. The morphology and organization of chondrocytes were studied using confocal microscopy. Glycosaminoglycan content was studied by micromass culture of chondrocytes of PKC-δ KO mice.ResultsWe uncovered atypical structural demarcation between articular cartilage and subchondral bone of PKC-δ KO mice. Histology analyses revealed a thickening of the articular cartilage and calcified bone–cartilage interface, and decreased safranin O staining accompanied by an increase in the number of hypertrophic chondrocytes in the articular cartilage of PKC-δ KO mice. Interestingly, loss of demarcation between articular cartilage and bone was concomitant with irregular chondrocyte morphology and arrangement. Consistently, in vivo calcein labeling assay showed an increased intensity of calcein labeling in the interface of the growth plate and metaphysis in PKC-δ KO mice. Furthermore, in vitro culture of chondrocyte micromass showed a decreased alcian blue staining of chondrocyte micromass in the PKC-δ KO mice, indicative of a reduced level of glycosaminoglycan production.ConclusionsOur data imply a role for PKC-δ in the osteochondral plasticity of the interface between articular cartilage and the osteochondral junction.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0720-4) contains supplementary material, which is available to authorized users. 相似文献2.
The clinical translation of tissue engineering approaches is limited by the requirement of a cell source. Cell guidance is a new concept that provides an alternative approach, obviating a requirement for an external cell source. This relies on site-specific homing and differentiation of the patient??s own cells to an implanted scaffold through controlled delivery of cytokines. In this study, we used stromal-cell-derived factor 1-alpha (SDF-1??) in combination with bone morphogenic protein (BMP)-2 or transforming growth factor (TGF)-??1 to induce cell migration and osteogenic or chondrogenic differentiation, respectively, in implanted scaffolds in a rat model. A customized cytokine microdelivery apparatus was used to ensure the constant rate and concentration of cytokine delivery around the scaffold. The formation of osteoid or early cartilage was observed after 4?weeks in specimens treated with SDF-1?? and either BMP-2 or TGF-??1. The density of cellular infiltrate and formation of differentiated tissue were lower in scaffolds treated only with BMP-2 or TGF-??1. Thus, controlled SDF-1?? delivery induces cell migration into scaffolds and can result in enhanced osteogenesis and chondrogenesis when used in combination with differentiation cytokines for purposes of tissue engineering. 相似文献
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Benjamin Liet Nicolas Nys Geraldine Siegfried 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2021,1868(9):119065
Elabela/toddler is the second endogenous ligand recently identified after Apelin, that binds to the G protein-coupled receptor APJ. Elabela is a 54-amino acid peptide initially identified in fish and human genomes and classified as noncoding. This precursor can be cleaved to shorter sequences (32, 21, and 11 amino acids), which bind and activate APJ, and can be blocked by APJ antagonists. Contrary to Apelin and APJ, widely distributed in organs and tissues, Elabela expression is more restricted, and different studies have revealed the potential role of Elabela in cancers. This review summarizes the current studies focusing on the role of Elabela in different cancers. 相似文献
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Didier Menard Ernest R. Chan Christophe Benedet Arsène Ratsimbasoa Saorin Kim Pheaktra Chim Catherine Do Benoit Witkowski Remy Durand Marc Thellier Carlo Severini Eric Legrand Lise Musset Bakri Y. M. Nour Odile Mercereau-Puijalon David Serre Peter A. Zimmerman 《PLoS neglected tropical diseases》2013,7(11)
Background
Plasmodium vivax is the most prevalent human malaria parasite, causing serious public health problems in malaria-endemic countries. Until recently the Duffy-negative blood group phenotype was considered to confer resistance to vivax malaria for most African ethnicities. We and others have reported that P. vivax strains in African countries from Madagascar to Mauritania display capacity to cause clinical vivax malaria in Duffy-negative people. New insights must now explain Duffy-independent P. vivax invasion of human erythrocytes.Methods/Principal Findings
Through recent whole genome sequencing we obtained ≥70× coverage of the P. vivax genome from five field-isolates, resulting in ≥93% of the Sal I reference sequenced at coverage greater than 20×. Combined with sequences from one additional Malagasy field isolate and from five monkey-adapted strains, we describe here identification of DNA sequence rearrangements in the P. vivax genome, including discovery of a duplication of the P. vivax Duffy binding protein (PvDBP) gene. A survey of Malagasy patients infected with P. vivax showed that the PvDBP duplication was present in numerous locations in Madagascar and found in over 50% of infected patients evaluated. Extended geographic surveys showed that the PvDBP duplication was detected frequently in vivax patients living in East Africa and in some residents of non-African P. vivax-endemic countries. Additionally, the PvDBP duplication was observed in travelers seeking treatment of vivax malaria upon returning home. PvDBP duplication prevalence was highest in west-central Madagascar sites where the highest frequencies of P. vivax-infected, Duffy-negative people were reported.Conclusions/Significance
The highly conserved nature of the sequence involved in the PvDBP duplication suggests that it has occurred in a recent evolutionary time frame. These data suggest that PvDBP, a merozoite surface protein involved in red cell adhesion is rapidly evolving, possibly in response to constraints imposed by erythrocyte Duffy negativity in some human populations. 相似文献5.
Wibke Singer Annalisa Zuccotti Mirko Jaumann Sze Chim Lee Rama Panford-Walsh Hao Xiong Ulrike Zimmermann Christoph Franz Hyun-Soon Geisler Iris Köpschall Karin Rohbock Ksenya Varakina Sandrine Verpoorten Thomas Reinbothe Thomas Schimmang Lukas Rüttiger Marlies Knipper 《Molecular neurobiology》2013,47(1):261-279
Increasing evidence shows that hearing loss is a risk factor for tinnitus and hyperacusis. Although both often coincide, a causal relationship between tinnitus and hyperacusis has not been shown. Currently, tinnitus and hyperacusis are assumed to be caused by elevated responsiveness in subcortical circuits. We examined both the impact of different degrees of cochlear damage and the influence of stress priming on tinnitus induction. We used (1) a behavioral animal model for tinnitus designed to minimize stress, (2) ribbon synapses in inner hair cells (IHCs) as a measure for deafferentation, (3) the integrity of auditory brainstem responses (ABR) to detect differences in stimulus-evoked neuronal activity, (4) the expression of the activity-regulated cytoskeletal protein, Arc, to identify long-lasting changes in network activity within the basolateral amygdala (BLA), hippocampal CA1, and auditory cortex (AC), and (5) stress priming to investigate the influence of corticosteroid on trauma-induced brain responses. We observed that IHC ribbon loss (deafferentation) leads to tinnitus when ABR functions remain reduced and Arc is not mobilized in the hippocampal CA1 and AC. If, however, ABR waves are functionally restored and Arc is mobilized, tinnitus does not occur. Both central response patterns were found to be independent of a profound threshold loss and could be shifted by the corticosterone level at the time of trauma. We, therefore, discuss the findings in the context of a history of stress that can trigger either an adaptive or nonadaptive brain response following injury. 相似文献
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Cedric P. Owens Nicholas Chim Amanda B. Graves Christine A. Harmston Angelina Iniguez Heidi Contreras Matthew D. Liptak Celia W. Goulding 《The Journal of biological chemistry》2013,288(30):21714-21728
Mycobacterium tuberculosis is the causative agent of tuberculosis, which is becoming an increasingly global public health problem due to the rise of drug-resistant strains. While residing in the human host, M. tuberculosis needs to acquire iron for its survival. M. tuberculosis has two iron uptake mechanisms, one that utilizes non-heme iron and another that taps into the vast host heme-iron pool. To date, proteins known to be involved in mycobacterial heme uptake are Rv0203, MmpL3, and MmpL11. Whereas Rv0203 transports heme across the bacterial periplasm or scavenges heme from host heme proteins, MmpL3 and MmpL11 are thought to transport heme across the membrane. In this work, we characterize the heme-binding properties of the predicted extracellular soluble E1 domains of both MmpL3 and MmpL11 utilizing absorption, electron paramagnetic resonance, and magnetic circular dichroism spectroscopic methods. Furthermore, we demonstrate that Rv0203 transfers heme to both MmpL3-E1 and MmpL11-E1 domains at a rate faster than passive heme dissociation from Rv0203. This work elucidates a key step in the mycobacterial uptake of heme, and it may be useful in the development of anti-tuberculosis drugs targeting this pathway. 相似文献
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Several investigators, including ourselves, have reported lower yield of GM-CSF bone marrow-derived dendritic cells (DC) with altered MHC class II and co-stimulatory molecules expression in the non-obese diabetic (NOD) mice. However, whether this defect was intrinsic to the DC lineage and/or related to abnormal expansion of other cell types responding to GM-CSF remained an opened issue. We performed phenotypical and morphological analysis of cells from GM-CSF-supplemented-bone marrow-cultures and of freshly isolated bone marrow and blood cells from unmanipulated prediabetic NOD mice. The results show a heretofore undescribed bias towards generation of granulocytes in NOD mice, concomitant with quantitative and qualitative alterations of the DC lineage in both the bone marrow and the blood of this mouse strain. We propose that increased generation of granulocytes in NOD mice might contribute to autoimmunity. First, high numbers of granulocytes per se might favor inflammatory environment. Second, granulocytes, by interfering with DC development, might favor unbalanced antigen presenting cell function leading to T cell autoimmunity. 相似文献
8.
Xinghuo Wu Shek Man Chim Vincent Kuek Bay Sie Lim Siu To Chow Jinmin Zhao Shuhua Yang Vicki Rosen Jennifer Tickner Jiake Xu 《FEBS letters》2014
Bone remodeling is regulated by secreted factors in the bone microenvironment. However, data regarding osteoclast-derived factors that influence osteoblast differentiation are lacking. Here, we show that HtrA1 is produced as a secreted protein during osteoclastogenesis, and negatively regulates osteoblast differentiation. Exogenous addition of recombinant HtrA1 attenuates osteoblast differentiation and BMP2-induced Smad1/5/8, ERK1/2 and p38 phosphorylation in pre-osteoblasts. Our studies imply a unique mode of crosstalk in which HtrA1 is produced by both osteoclasts and osteoblasts and negatively regulates osteoblast differentiation, suggesting that HtrA1 may mediate the fine tuning of paracrine and autocrine regulations during bone remodeling processes. 相似文献
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