Research progress of tunneling nanotube in bone biology / 中华口腔医学杂志

Tunneling nanotube (TNT) is a newly discovered communication mode between animal cells in recent years, which have important physiological and pathological significance. However, the role of TNT in bone biology is still unclear. At present, there are many reports about tunneling nanotubes in bone marrow mesenchymal stem cells, osteoclast precursor cells, osteoblasts and immune cells. This review describes the research advances of TNT and its research progress in bone biology. It looks forward to the research direction of TNT in oral and maxillofacial bone development and bone biology, to provide new strategies for the maintenance of bone homeostasis and the treatment of bone diseases.

Extracellular signals regulate the biogenesis of extracellular vesicles

Extracellular vesicles (EVs) are naturally released membrane vesicles that act as carriers of proteins and RNAs for intercellular communication. With various biomolecules and specific ligands, EV has represented a novel form of information transfer, which possesses extremely outstanding efficiency and specificity compared to the classical signal transduction. In addition, EV has extended the concept of signal transduction to intercellular aspect by working as the collection of extracellular information. Therefore, the functions of EVs have been extensively characterized and EVs exhibit an exciting prospect for clinical applications. However, the biogenesis of EVs and, in particular, the regulation of this process by extracellular signals, which are essential to conduct further studies and support optimal utility, remain unclear. Here, we review the current understanding of the biogenesis of EVs, focus on the regulation of this process by extracellular signals and discuss their therapeutic value.

The role of under-investigated connexins in musculoskeletal tissue: a brief review with emphasis on bone tissue / El papel de las escasamente investigadas conexinas en el tejido músculo-esquelético: una breve revisión con énfasis en el tejido óseo

Connexins (Cxs) are a family of transmembrane proteins that form gap junctions and hemi-channels, which mediate cell-cell communication between neighboring cells and the respective extracellular milieu in different tissues. Most tissues and cell types throughout the body express one or more Cx proteins, highlighting its importance in regulating cell growth, differentiation, adhesion, migration, cell death and others. Moreover, Cx can propagate intracellular signals through its C-terminus domain, and thus function beyond a mere channel. Cx43 is the most highly expressed and most well studied Cx in bone and musculoskeletal tissues, although Cx40, Cx45, Cx46 and more recently, the Cx37 have been described in bone tissue, along with Cx26, Cx32 and Cx39 in other musculoskeletal tissues. Here, we discuss the basic structure of gap junctions and the role of the Cxs in musculoskeletal tissue, with special focus on Cx37. (AU)

Las conexinas (Cxs) son una familia de proteínas transmembrana que forman uniones en hendidura y hemicanales encargados de mediar la comunicación entre células vecinas y el respectivo medio extracelular en diferentes tejidos. La mayoría de los tejidos y células expresan una o más proteínas conexina, jugando un papel importante en la regulación de la proliferación celular, diferenciación, adhesión, migración y muerte celular, entre otras funciones. Además de actuar como un canal, las conexinas pueden propagar señales intracelulares a través del dominio C-terminal. La Cx43 es la conexina mas expresada y mejor estudiada en el tejido óseo y el músculo, aunque las Cx40, Cx45, Cx46, y mas recientemente Cx37, son también detectadas en el hueso. A su vez la expresión de la Cx26, Cx32 y Cx39 ha sido observada en otros tejidos músculoesqueléticos. En este manuscrito describimos la estructura básica de las uniones tipo gap y el papel que las Cxs, y en especial la Cx37, tienen en tejidos músculo-esqueléticos. (AU)

Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment

OBJECTIVES: Experimental studies on sepsis have demonstrated that ethyl pyruvate is endowed with antioxidant and anti-inflammatory properties. This study aimed to investigate the effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation in a live Escherichia coli-induced sepsis model in rats. METHODS: Male Wistar rats were administered an intravenous suspension of E. coli bacteria or were subjected to a sham procedure. Three hours after bacterial infusion, the rats were randomized into the following groups: a control group without treatment, a group treated with lactated Ringer’s solution (4 mL/kg, i.v.), and a group treated with lactated Ringer’s solution (4 mL/kg, i.v.) plus ethyl pyruvate (50 mg/kg). At 24 h after bacterial infusion, leukocyte-endothelial interactions were investigated using intravital microscopy, and the expression of P-selectin and intercellular adhesion molecule-1 was evaluated via immunohistochemistry. White blood cell and platelet counts were also determined at baseline and 3 h and 24 h after E. coli inoculation. RESULTS: The non-treated and lactated Ringer’s solution-treated groups exhibited increases in the numbers of rolling leukocytes (∼2.5-fold increase), adherent cells (∼3.0-fold), and migrated cells (∼3.5-fold) compared with the sham group. In contrast, treatment with Ringer’s ethyl pyruvate solution reduced the numbers of rolling, adherent and migrated leukocytes to the levels observed in the sham group. Additionally, the expression of P-selectin and intercellular adhesion molecule-1 was significantly increased on mesenteric microvessels in the non-treated group compared with the sham group (p<0.001). The expression of both adhesion molecules was reduced in the other groups, with ethyl pyruvate being more effective than lactated Ringer’s solution. Infusion of bacteria caused significant leukopenia (3 h), followed ...

A low-protein diet during pregnancy prevents modifications in intercellular communication proteins in rat islets

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Fibronectin modulates thymocyte-thymic epithelial cell interactions following Trypanosoma cruzi infection

Developing thymocytes interact with thymic epithelial cells (TECs) through cell-cell interactions, TEC-derived secretory moieties and extracellular matrix (ECM)-mediated interactions. These physiological interactions are crucial for normal thymocyte differentiation, but can be disrupted in pathological situations. Indeed, there is severe thymic atrophy in animals acutely infected with Trypanosoma cruzi due to CD4+CD8+ thymocyte depletion secondary to caspase-mediated apoptosis, together with changes in ECM deposition and thymocyte migration. We studied an in vitro model of TEC infection by T. cruzi and found that infected TEC cultures show a reduced number of cells, which was likely associated with decreased proliferative capacity, but not with increased cell death, as demonstrated by bromodeoxyuridine and annexin-V labelling. The infected TEC cultures exhibited increased expression of fibronectin (FN), laminin (LM) and type IV collagen. Importantly, treatment with FN increased the relative number of infected cells, whereas treatment with anti-FN or anti-LM antibodies resulted in lower infection rates. Consistent with these data, we observed increased thymocyte adhesion to infected TEC cultures. Overall, these results suggest that ECM molecules, particularly FN, facilitate infection of the thymic epithelium and that the consequent enhancement of ECM expression might be associated with changes in TEC-thymocyte interactions.

Extracellular vesicles: structure, function, and potential clinical uses in renal diseases

Interest in the role of extracellular vesicles in various diseases including cancer has been increasing. Extracellular vesicles include microvesicles, exosomes, apoptotic bodies, and argosomes, and are classified by size, content, synthesis, and function. Currently, the best characterized are exosomes and microvesicles. Exosomes are small vesicles (40-100 nm) involved in intercellular communication regardless of the distance between them. They are found in various biological fluids such as plasma, serum, and breast milk, and are formed from multivesicular bodies through the inward budding of the endosome membrane. Microvesicles are 100-1000 nm vesicles released from the cell by the outward budding of the plasma membrane. The therapeutic potential of extracellular vesicles is very broad, with applications including a route of drug delivery and as biomarkers for diagnosis. Extracellular vesicles extracted from stem cells may be used for treatment of many diseases including kidney diseases. This review highlights mechanisms of synthesis and function, and the potential uses of well-characterized extracellular vesicles, mainly exosomes, with a special focus on renal functions and diseases.

Exosomes: mediators of communication in eukaryotes

In addition to the established mechanisms of intercellular signaling, a new way of communication has gained much attention in the last decade: communication mediated by exosomes. Exosomes are nanovesicles (with a diameter of 40-120 nm) secreted into the extracellular space by the multivesicular endosome after its outer membrane fuses with the plasma membrane. Once released, exosomes modulate the response of the recipient cells that recognize them. This indicates that exosomes operate in a specific manner and participate in the regulation of the target cell. Remarkably, exosomes occur from unicellular organisms to mammals, suggesting an evolutionarily conserved mechanism of communication. In this review we describe the cascade of exosome formation, intracellular traffic, secretion, and internalization by recipient cells, and review their most relevant effects. We also highlight important steps that are still poorly understood.

Cell-cell communication between mouse mammary epithelial cells and 3T3-L1 preadipocytes: effect on triglyceride accumulation and cell proliferation

Interaction between parenchyma and stroma is essential for organogenesis, morphogenesis, and differentiation. Mammary gland has being the chosen model for developmental biologist because the most striking changes in morphology and function take place after birth. We have demonstrated a regulation of triglyceride accumulation by protein factors synthesized by normal mouse mammary gland epithelial cells (NMMG), acting on a cell line, 3T3-L1, long used as a model for adipogenesis. In this paper, we demonstrate that this inhibitory effect seems to be shared by other cells of epithelial origin but not by other cell types. We found a regulation of cell proliferation when NMMG cells are cultured in the presence of conditioned media from Swiss 3T3 or 3T3-L1 cells. We found a possible point of regulation for the mammary factor on a key enzyme of the lipid metabolic pathway, the glycerol-3-phosphate dehydrogenase. The inhibitory factor seems to have an effect on this enzyme's activity and reduces it. The results presented herein contribute to the understanding of cell-cell communication in a model of a normal mammary gland.

The Role of Activated Hepatic Stellate Cells in Liver Fibrosis, Portal Hypertension and Cancer Angiogenesis / 대한간학회지

Although hepatic stellate cells, which are liver specific pericytes, have been recognized within the vasculature of the sinusoid for more than one hundred years, the biology and function of these cells is unclear. Recent studies have highlighted the key role of stellate cells in a number of fundamental processes that include wound healing/fibrosis, vasoregulation, and vascular remodeling/angiogenesis. In the liver, these processes are particularly important in the development of cirrhosis, portal hypertension and cancer. This article highlights the recent advances in our understanding of the biology of hepatic stellate cells and discusses some of the recently-ascribed functions that are relevant to liver fibrosis, portal hypertension and cancer angiogenesis.

Plasmodemos: estructura y funcion / Plasmodesmata: Structure and Function

Los plasmodesmos son canales que atraviesan la membrana y la pared celular. Estos canales especializados y no pasivos, actúan como compuertas que facilitan y regulan la comunicación y el transporte de sustancias como agua, nutrientes, metabolitos y macromoléculas entre las células vegetales. En los últimos años, una nueva visión sobre estos canales ha surgido y, estudios han demostrado que los plasmodesmos son más complejos de lo que anteriormente se pensaba. En esta nota, se pretende exponer el conocimiento actual sobre dichas estructuras, enfocándonos en su estructura y función.

Aplicación de una cámara de flujo para el análisis de la aglutinación eritrocitaria mediada por anticuerpos monoclonales / Application of the flow chamber technique to the analysis of the erythrocyte agglutination mediated by monoclonal antibodies

El conocimiento de la energía involucrada en las interacciones célula-célula tiene importantes implicaciones en las ciencias biológicas y médicas. Los glóbulos rojos se adhieren entre si cuando macromoléculas específicas o no específicas (aglutininas) enlazan células adyacentes de manera irreversible o reversible. La técnica de la cámara de flujo fue utilizada para evaluar la afinidad de un anticuerpo monoclonal analizando la disociación de un doblete (dos células aglutinadas por el anticuerpo) determinando la energía de adhesión. Esta técnica permite aplicar una tensión de corte uniforme paralela a la interfase de adhesión de un aglutinado de dos células fijado sobre la superficie inferior de un microcanal. La tensión produce el desprendimiento progresivo de la célula superior del doblete. La observación microscópica de la separación producida en el aglutinado aislado y la obtención de imágenes secuenciales con una cámara CCD (Charged Coupled Device), permite determinar la relación entre la tensión de corte aplicada (sigma) y el porcentaje de separación de las células del doblete. A partir de estos resultados calculamos la energía de disociación por unidad de área membranal adherida(gamma d), valor igual a 8.92 x 10 elevado a -19 N.cm por moléculas de anticuerpo. Del análisis de los resultados, se concluye que la tensión de corte necesaria para disociar el doblete es proporcional a la densidad superficial de moléculas de anticuerpo y a la densidad antigénica de los eritrocitos.

Rincones olvidados de la gastroenterología: las células intersticiales de Cajal / Forgotten corners of the gastrointestinal tract: interstitial cells of Cajal

Las células musculares lisas del tubo digestivo tienen tanto actividad eléctrica como mecánica. La contracción coordinada es regulada por un ritmo de marcapasos. La actividad eléctrica de marcapasos no es una propiedad intrínseca de la célula muscular, sino que es generada por un grupo especializado de otras células, dispuestas en una red entrelazada con los miocitos que se han denominado células intersticiales de Cajal, en honor del científico español Santiago Ramón y Cajal, quien las describiera en el siglo XIX. En el tubo digestivo esta red esta ubicada cerca del plexo mientérico y genera potenciales de marcapasos cuyos potenciales se transmiten pasivamente hacia las capas musculares vecinas donde generan cambios rítmicos en su potencial de membrana. El concepto actual es que los nervios autonómicos no contactan directamente con los miocitos para liberar sus neurotransmisores y así regular la función motora del tubo digestivo. En cambio, se contactan con las células de Cajal a través de sinapsis y éstas, a su vez, contactan con los miocitos vecinos. Por lo tanto, las células de Cajal son las responsables de recibir (¿y modular?) los estímulos, tanto excitatorios como inhibitorios. El estudio de sus alteraciones está mejorando nuestros conocimientos de diferentes trastornos motores del tubo digestivo. Pero además, las células de Cajal son el origen de las líneas celulares que dan lugar a los tumores estromales del tubo digestivo (GIST o gastrointestinal stromal tumors). Esta información no sólo nos da una mejor comprensión de la fisiología sino que además, permite diseñar terapias para estos tumores, en la medida que se conocen las bases moleculares y genéticas de esta transformación.

Regulation of astroglia on synaptic plasticity in the CA1 region of rat hippocampus / 华中科技大学学报（医学）（英德文版）

The regulation of astroglia on synaptic plasticity in the CA1 region of rat hippocampus was examined. Rats were divided into three groups: the newly born (< 24 h), the juvenile (28-30 days) and the adult groups (90 - 100 days), with each group having 20 animals. The CA1 region of rat hippocampus was immunohistochemically and electron-microscopically examined, respectively, for the growth of astroglia and the ultrastructure of synapses. The high performance liquid chromatography was employed to determine the cholesterol content of rat hippocampus. In the newly-born rats, a large number of neurons were noted in the hippocampal CA1 region of the newly-born rats, and few astroglia and no synaptic structure were observed. In the juvenile group, a few astroglias and some immature synapses were found, which were less than those in adult rats (P < 0.01). The cholesterol content was 2.92 +/- 0.03 mg/g, 11.20 +/- 3.41 mg/g and 12.91 +/- 1.25 mg/g for newly born, the juvenile and the adult groups, respectively, with the differences among them being statistically significant (P < 0.01). Our study suggests that the astrocytes may play an important role in the synaptic formation and functional maturity of hippocampal neurons, which may be related to the secretion of cholesterol from astrocytes.

Gap junctions, connexins and sudden death caused by coronary heart disease / 法医学杂志

Gap junctions construct hydrophilic trans-membrane channels which adjust the intercellular communication of chemistry and electricity. In the heart, individual cardiac myocytes are linked by gap junctions. These junctions form low resistance pathways along which the electrical impulse flows rapidly and repeatedly between all the myocardium, ensuring their synchronous contraction. In recent years, some researchers have found that connexins, the protein molecules of gap junction channels, are reduced in number or redistributed from intercalated disks (ID) to lateral cell borders in a variety of cardiac disease, especially in ischemic heart disease. The gap junction remodeling is considered to be arrhythmogenic. These findings will lead us to a new realm in the diagnostic of sudden death caused by coronary heart disease.

Local and global Ca2+ signals: physiology and pathophysiology

The pancreatic acinar unit is a classical example of a polarized tissue. Even in isolation, these cells retain their polarity, and this has made them particularly useful for Ca2+ signaling studies. In 1990, we discovered that this cell has the capability of producing both local cytosolic and global Ca2+ signals. The mechanisms underlying this signal generation have now been established. Furthermore, it has become clear that the local signals are sufficient for the control of both fluid and enzyme secretion, whereas prolonged global signals are dangerous and give rise to acute pancreatitis, a disease where the pancreas digests itself.

Interação entre células tubulares renais, cristais de oxalato de cálcio e íons oxalato: efeitos sobre a síntese de glicosaminoglicanos / Interaction between tubular epithelial cells, calcium oxalate crystals and oxalate ions: effects upon the synthesis of glycosaminoglycans

A interação entre as células tubulares renais, os cristais de oxalato de cálcio (CaOx) e os íons oxalato é um evento precoce na litogênese. A urina contém íons, glicoproteínas e glicosaminoglicanos que inibem o processo de cristalização e protegem o rim contra a litogênese. Examinamos o efeito dos cristais de oxalato de cálcio e íons oxalato sobre a síntese de glicosaminoglicanos em células tubulares distais (MDCK) e proximais (LLCPK1). A síntese de glicosaminoglicanos foi analisada por meio de marcação metabólica com 35S-sulfato e degradação enzimática com mucopolissacaridases específicas. 0 tipo de morte celular (necrose ou apoptose) foi detectado por meio de sondas fluorescentes e a endocitose dos cristais de CaOx foi analisado por meio de citometria de fluxo. Os principais glicosaminoglicanos sintetizados em ambas as células foram condroitim sulfato e heparam sulfato, a maioria secretada para o meio de cultura ou presente na superfície celular. Pequenas quantidades de ácido hialurônico também foram detectadas. A exposição de células MDCK aos íons oxalato aumentou a porcentagem de apoptose e a incorporação de 35S-sulfato no condroitim sulfato e heparam sulfato, além de induzir um pequeno aumento na concentração de ácido hialurônico. Os cristais de CaOx foram endocitados pelas células LLC-PK1, induziram morte celular por necrose, aumentaram a incorporação de 35S-sulfato nos glicosaminoglicanos. Estes feitos parecem ser específicos para estes sais porque a hidroxiapatita e outro ácido carboxílico não induziram morte celular ou aumento na síntese de glicosaminoglicanos. Adicionalmente estes efeitos podem ser atribuídos ao aumento da biossíntese, pois não foram detectados mudanças no grau de sulfatação ou no peso molecular dos glicosaminoglicanos. Tapsigargina bloqueou o aumento no condroitim sulfato e heparam sulfato induzido pelo CaOx em LLC-PK1, sugerindo que a síntese de glicosaminoglicanos estimulada pelo CaOx é sensível ao aumento do cálcio intracelular. As células do epitélio tubular renal são o alvo principal dos efeitos induzidos pela hiperoxalúria e pela incorporação de cristais CaOx. Uma vez que o dano às células tubulares predispõe a nucleação, talvez o aumento na síntese de glicosaminoglicanos proteja o epitélio tubular contra a adesão dos cristais e o efeito tóxico da hiperoxalúria, o que poderia limitar a formação do cálculo renal

Cross-talk between neurons and glia: highlights on soluble factors

The development of the nervous system is guided by a balanced action between intrinsic factors represented by the genetic program and epigenetic factors characterized by cell-cell interactions which neural cells might perform throughout nervous system morphogenesis. Highly relevant among them are neuron-glia interactions. Several soluble factors secreted by either glial or neuronal cells have been implicated in the mutual influence these cells exert on each other. In this review, we will focus our attention on recent advances in the understanding of the role of glial and neuronal trophic factors in nervous system development. We will argue that the functional architecture of the brain depends on an intimate neuron-glia partnership