Browsing by Subject "Cartilage"

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    Adipose-derived stem cells in articular cartilage regeneration: current concepts and optimization strategies
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Gu, Xingjian; Li, Caixin; Yin, Feng; Yang, Guanghua
    Knee osteoarthritis (KOA) is the most common progressive joint disorder associated with disability in the world. As a chronic disease, KOA has multifactorial etiology. However, the poor self-healing ability of the articular cartilage due to its intrinsic tissue hypovascularity and hypocellularity seems to be directly incriminated in the physio-pathological mechanism of KOA. While conventional therapies result in unfavorable clinical outcomes, regenerative cell therapies have shown great promise in articular cartilage regeneration. Adipose-derived stem cells (ASCs) appear to be an ideal alternative to bone-marrow derived stem cells (BMSCs) and autologous chondrocytes, due to their lower immunogenicity, richer source and easier acquisition. Since the first case report in 2011, ASCs have demonstrated safety and efficacy for articular cartilage regeneration in several phase I/II clinical trials. However, different levels of abnormality were found in the regenerated cartilage for most of the patients. A large portion of recent publications investigated different optimization strategies to improve the therapeutic function of ASCs, including cell source selection, preconditioning and co-delivery. Herein, we give an update on the latest research progress on ASCs, with a focus on the most promising optimization strategies for ASC-based therapy.
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    Age-related degeneration of articular cartilage in the pathogenesis of osteoarthritis: molecular markers of senescent chondrocytes
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Musumeci, Giuseppe; Szychlinska, Marta Anna; Mobasheri, Ali
    Aging is a natural process by which every single living organism approaches its twilight of existence in a natural way. However, aging is also linked to the pathogenesis of a number of complex diseases. This is the case for osteoarthritis (OA), where age is considered to be a major risk factor of this important and increasingly common joint disorder. Half of the world's population, aged 65 and older, suffers from OA. Although the relationship between the development of OA and aging has not yet been completely understood, it is thought that age-related changes correlate with other risk factors. The most prominent hypothesis linking aging and OA is that chondrocytes undergo premature aging due to several factors, such as excessive mechanical load or oxidative stress, which induce the so called “stress-induced senescent state”, which is ultimately responsible for the onset of OA. This review focuses on molecular markers and mechanisms implicated in chondrocyte aging and the pathogenesis of OA. We discuss the most important age-related morphological and biological changes that affect articular cartilage and chondrocytes. We also identify the main senescence markers that may be used to recognize molecular alterations in the extracellular matrix of cartilage as related to senescence. Since the aging process is strongly associated with the onset of osteoarthritis, we believe that strategies aimed at preventing chondrocyte senescence, as well as the identification of new increasingly sensitive senescent markers, could have a positive impact on the development of new therapies for this severe disease.
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    Brefeldin A influences the cell surface abundance and intracellular pools of low and high ouabain affinity Na+, K+-ATPase cx subunit isoforms in articular chondrocytes
    (Murcia : F. Hernández, 1999) Mobasheri, A.
    The catalytic a isoforms of the Na+, K+- ATPase and stimuli controlling the plasma membrane abundance and intracellular distribution of the enzyme were studied in isolated bovine articular chondrocytes which have previously been shown to express low and high ouabain affinity a isoforms (a1 and a 3 respectively; al>>a3). The Naf, K+-ATPase density of isolated chondrocyte preparations was quantified by specific 3 ~ - ouabain binding. Long-term elevation of extracellular medium [Na+] resulted in a significant (31%; p<0.05) upregulation of Na+, K+-ATPase density and treatment with various pharmacological inhibitors (Rrefeldin A, monensin and cycloheximide) significantly @<0.001) blocked the upregulation. The subcellular distribution of the NaC, K+-ATPase a isoforms was examined by immunofluorescence confocal laser scanning microscopy which revealed predominantly plasma membrane immunostaining of a subunits in control chondrocytes. In Brefeldin A treated chondrocytes exposed to high [Na+], Na+, K+-ATPase a isoforms accumulated in juxta-nuclear pools and plasma membrane Na+, K+- ATPase density monitored by 3~-ouaba inb inding was significantly down-regulated due to Brefeldin A mediated disruption of vesicular transport. There was a marked increase in intracellular a 1 and a3 staining suggesting that these isoforms are preferentially upregulated following long-term exposure to high extracellular [Na+]. The results demonstrate that Na+, K+-ATPase density in chondrocytes is elevated in response to increased extracellular [Na+] through de novo protein synthesis of new pumps containing a 1 and a 3 isoforms, delivery via the endoplasrnic reticulum- Golgi complex constitutive secretory pathway and insertion into the plasma membrane.
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    Distribution of CD105 and CD166 positive cells in the proximal epiphysis of developing rat humerus
    (Murcia : F. Hernández, 2010) Ozbey, Ozlem; Sahin, Zeliha; Acar, Nuray; Ustunel, Ismail
    The expression of cell surface receptors, CD105 and CD166, are characteristic of mesenchymal stem cells in cartilage. However, there is limited data regarding their immunolocalization in the cartilage of developing rat epiphysis. The purpose of this study was to determine the presence of CD105 and CD 166 positive cells in the proximal epiphysis of developing rat humerus and specify their zonal distribution with age. The tissues of rat humerus were taken on embryonic day 15 (E15), embryonic day 19 (E19), postnatal day 10 (PN10), postnatal day 20 (PN20) and adult rats and studied for the immunolocalization of CD105 and CD166. Our results showed that CD105 and CD166 positive cells were scattered in early stages of development of humerus epiphysis. For E15, only the hypertrophic zone was positive, whereas for E19 almost all zones of the epiphysis were positively stained for these markers. For PN10 and PN20, the CD105 and CD166 positive cells were mainly localized on the surface of the articular cartilage. In adult articular cartilage the CD105 and CD166 positive cells were localized in the superficial and transitional zones and in the upper regions of the deep zone. Our study provides evidence that in the developing cartilage tissue the localization of CD105 and CD166 positive cells is both dynamic and stage dependent, which may imply the existence of stem cell-like cells in cartilage from an early age to adult.
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    Glucose transport and metabolism in chondrocytes: a key to understanding chondrogenesis, skeletal development and cartilage degradation in osteoarthritis
    (Murcia : F. Hernández, 2002) Mobasheri, A.; Vannucci, S.J.; Bondy, C.A.; Carter, S.D.; Innes, J.F.; Arteaga, M.F.; Trujillo, E.; Ferraz, I.; Shakibaei, M.; Martín Vasallo, P.
    Despite the recognition that degenerative cartilage disorders like osteoarthritis (OA) and osteochondritis dissecans (OCD) may have nutritional abnormalities at the root of their pathogenesis, balanced dietary supplementation programs have played a secondary role in their management. This review emphasizes the importance and role of nutritional factors such as glucose and glucose-derived sugars (i.e. glucosamine sulfate and vitamin C) in the development, maintenance, repair, and remodeling of cartilage. Chondrocytes, the cells of cartilage, consume glucose as a primary substrate for ATP production in glycolysis and utilize glucosamine sulfate and other sulfated sugars as structural components for extracellular matrix synthesis and are dependant on hexose uptake and delivery to metabolic and biosynthetic pools. Data from several laboratories suggests that chondrocytes express multiple isoforms of the GLUT/SLC2A family of glucose/polyol transporters. These facilitative glucose transporter proteins are expressed in a tissue and cell-specific manner, exhibit distinct kinetic properties, and are developmentally regulated. They may also be regulated by endocrine factors like insulin and insulin-like growth factor I (IGF-I) and cytokines such as interleukin 1 beta (IL-1ß) and tumour necrosis factor alpha (TNF-a). Recent studies suggest that degeneration of cartilage may be triggered by metabolic disorders of glucose balance and that OA occurs coincident with metabolic disease, endocrine dysfunction and diabetes mellitus. Based on these metabolic, endocrine and developmental considerations we present a novel hypothesis regarding the role of glucose transport and metabolism in cartilage physiology and pathophysiology and speculate that supplementation with sugar-derived vitamins and nutraceuticals may benefit patients with degenerative joint disorders.
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    Ion transport in chondrocytes, membrane transporters involved in intracellular ion homeostasis and the regulation of cell volume, free [Ca2+] and pH
    (Murcia : F. Hernández, 1998) Mobasheri, A.; Mobasheri, R.; Francis, M.J.O.; Trujillo, E.; Alvarez de la Rosa, D.; Martín Vasallo, P.
    Chondrocytes exist in an unusual and variable ionic and osmotic environment in the extracellular matrix of cartilage and are responsible for maintaining the delicate equilibrium between extracellular matrix synthesis and degradation. The mechanical performance of cartilage relies on the biochemical properties of the matrix. Alterations to the ionic and osmotic extracellular environment of chondrocytes have been shown to influence the volume, intracellular pH and ionic content of the cells, which in turn modify the synthesis and degradation of extracellular matrix macromolecules. Physiological ion homeostasis is fundamental to the routine functioning of cartilage and the factors that control the integrity of this highly evolved and specialized tissue. Ion transport in cartilage is relatively unexplored and the biochemical properties and molecular identity of membrane transport mechanisms employed by chondrocytes in the control of intracellular ion concentrations and pH is not fully defined and this review focuses on these processes. Chondrocytes have been shown to express voltage and stretch activated ion channels, passive exchangers and ATP dependent ion pumps. In addition, recent studies of transport systems in chondrocytes have demonstrated the presence of isozyme diversity that includes Na+/H+ exchange (NHE1, NHE3), Na+, K+-ATPase (several isoforms) and others each of which possess considerably different kinetic properties and modes of regulation. This multitude of isozyme diversity indicates the highly specialized handling of ions and protons in order to accomplish a fine regulation of their transmembrane fluxes. The complexities of these transport systems and their patterns of isoform expression underscore the subtlety of ion homeostasis and pH regulation in normal cartilage. Perturbations in these mechanisms may affect the physiological turnover of cartilage and thus increase the susceptibility to degenerative joint disease.
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    Platelet rich plasma: a valid augmentation for cartilage scaffolds? a systematic review
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Perdisa, Francesco; Filardo, Giuseppe; Di Matteo, Berardo; Marcacci, Maurilio; Kon, Elizaveta
    It has been shown that modern regenerative scaffold-based procedures for the treatment of articular cartilage defects offer good clinical results, although the properties of native healthy cartilage have not yet been matched by any substitute. Several implants have been tested and clinically used over the years to promote articular surface restoration, some of them producing a hyaline-like reparative tissue. There has been an increase in the number of new biological strategies, alone and in combination with scaffolds, to enhance the clinical outcome in patients with chondral disease. Among these innovative methods, one of the most widely used is Platelet-rich Plasma (PRP), based on the rationale of using the growth factors contained in platelet alpha granules to promote tissue regeneration. The aim of the present manuscript is to review systematically the current evidence in pre-clinical and clinical studies for the use of PRP augmented scaffolds to treat chondral or osteochondral disorders.
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    Presence and possible function of Zn in the hyaline cartilage
    (Murcia : F. Hernández, 1991) Pérez Castejón, M.C.; Barral, M.J.; Vera Gil, A.; Pérez Castejón, M.J.; Lahoz, M.
    Using histochemical and autoradiographical techniques the location of Zn in the hyaline cartilage of the Wistar rat was studied. A triple location was observed in the territorial matrix; in the chondrocyte; and in the perichondrio (cellular area). We believe that the molecules which were observed carrying Zn could be alkaline phosphatase, timidin-kinase and chondroitinsulphuric acid.
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    Semiquantitative analysis of ECM molecules in the different cartilage layers in early and advanced osteoarthritis of the knee joint
    (2012) Lahm, Andreas; Kasch, Richard; Mrosek, Eike; Spank, Heiko; Erggelet, Christoph; Esser, Jan; Merk, Harry
    The study was conducted to examine the expression of collagen type I and II in the different cartilage layers in relation to other ECM molecules during the progression of early osteoarthritic degeneration in human articular cartilage (AC). Quantitative real-time (RT)-PCR and colorimetrical techniques were used for calibration of Photoshop-based image analysis in detecting such lesions. Immunohistochemistry and histology were performed with 40 cartilage tissue samples showing mild (ICRS grade 1b) respectively moderate/advanced (ICRS grade 3a or 3b) (20 each) osteoarthritis compared with 15 healthy biopsies. Furthermore, we quantified our results on the gene expression of collagen type I and II and aggrecan with the help of real-time (RT)-PCR. Proteoglycan content was measured colorimetrically. The digitized images of histology and immunohisto-chemistry stains were analyzed with Photoshop software. T-test and Spearman correlation analysis were used for statistical analysis. In the earliest stages of AC deterioration the loss of collagen type II was associated with the appearance of collagen type I, shown by increasing amounts of collagen type I mRNA. During subsequent stages, a progressive loss of structural integrity was associated with increasing deposition of collagen type I as part of a natural healing response. A decrease of collagen type II is visible especially in the upper fibrillated area of the advanced osteoarthritic samples, which then leads to an overall decrease. Analysis of proteoglycan showed losses of the overall content and a loss of the classical zonal formation. Correlation analysis of the proteoglycan Photoshop measurements with the RT-PCR revealed strong correlation for Safranin O and collagen type I, medium for collagen type II, alcian blue and glycoprotein but weak correlation with PCR aggrecan results. Photoshop based image analysis might become a valuable supplement for well known histopathological grading systems of lesioned articular cartilage. The evidence of collagen type I production early in the OA disease process coupled with the ability of chondrocytes to up-regulate collagen type II production suggests that therapeutic agents that suppress collagen type I production and increase collagen type II production may enable chondrocytes to generate a more effective repair response
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    Similarities and differences of estrogen in the regulation of temporomandibular joint osteoarthritis and knee osteoarthritis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Tian, Yajing; Cui, Shengjie; Guo, Yanning; Zhao, Ningrui; Gan, Yehua; Zhou, Yanheng; Wang, Xuedong
    Background. Temporomandibular joint osteoarthritis (TMJOA) and knee osteoarthritis (knee OA) are two kinds of common osteoarthritis (OA) that are characterized by chronic degeneration of soft and hard tissues around joints. Their gender and age differences suggest that there are similarities and differences between the pathogenic mechanisms of TMJOA and knee OA. Objective. To review recent studies on the effect of estrogen on TMJOA and knee OA, and summarize their possible pathogenesis and molecular mechanisms. Sources. Articles up to present reporting the relationship of estrogen and TMJOA or knee OA are included. An extensive electronic search was conducted of databases including PubMed, Web of science core collection. Conclusion. According to epidemiological investigations, TMJOA primarily happens to females of puberty and childbearing age, while knee OA mainly affects postmenopausal women. Epidemiological investigation and experimental research suggest that estrogen may have a different effect on TMJ and on knee. Though estrogen regulates TMJOA and knee OA via estrogen-related receptors (ERR), their pathogenesis and pathway of estrogen regulation are different. To find out the accurate regulation of estrogen on TMJOA and knee OA, specific pathways and molecular mechanisms still need further exploration.