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1.
J Cell Mol Med ; 28(3): e18107, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38235989

RESUMEN

Accelerated telomere shortening is associated with age-related diseases, including osteoarthritis (OA). We aimed to determine the relative telomere length (TL) in leukocytes and cartilage of patients with primary knee OA and to investigate factors that may affect TL in OA. Relative TL measurements were performed using qPCR in leukocytes of 612 individuals (310 patients with primary knee OA undergoing total knee arthroplasty (TKA) and 302 unaffected controls). We also analysed cartilage in 57 of the 310 OA patients, measuring relative TL in severely affected and less affected (control) cartilage collected from the same knee. Cartilage TLs were compared to leukocyte TLs in all 57 patients. A significant sex-by-disease-status interaction was found in regard to relative TL. Controlling for age, the average difference of leukocyte TL between female OA patients versus female controls was 0.217 units greater than that between male OA patients versus male controls (95% CI; [0.014, 0.421]). Relative TL comparison of severely and less affected cartilage samples from the same joint showed attrition of telomeres corresponding to disease severity (0.345 mean TL difference with 95% CI of [0.151, 0.539]) in the joint. We also noted that both severely and less affected cartilage had shorter telomeres than leukocytes collected from the same patient. Severe and moderate pain in OA patients was associated with shorter TL in leukocytes, but there was no association with depression or smoking in leukocytes and cartilage. Our study indicates that sex is an important factor in OA contributing to leukocyte and cartilage TL and that pain in OA shows an inverse association only with leukocyte TL.


Asunto(s)
Osteoartritis de la Rodilla , Humanos , Masculino , Femenino , Acortamiento del Telómero , Telómero , Leucocitos , Dolor
2.
Biochem Biophys Res Commun ; 730: 150392, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39003867

RESUMEN

BACKGROUND: One of the obstacles to autologous chondrocyte implantation (ACI) is obtaining a large quantity of chondrocytes without depletion of their properties. The conditioned medium (CM) from different subpopulations of stem cells (mesenchymal stromal cells (MSC) or induced pluripotent stem cells (iPSC)) could be a gamechanger. MSCs' potential is related to the donor's health and age, which could be omitted when, as a source, iPSCs are used. There is a lack of data regarding their use in the chondrocyte culture expansion. Thus, we wanted to verify whether iPSC-CM could be beneficial for the cell culture of primary chondrocyte cells. METHODS: We added the iPSC-CMs from GPCCi001-A and ND 41658*H cells to the culture of primary chondrocyte cell lines isolated from OA patients (n = 6) for other two passages. The composition of the CM was evaluated using Luminex technology. Then, we analysed the senescence, proliferation rate and using flow cytometry: viability, distribution of cell cycle phases, production of reactive oxygen species (ROS) and double-strand breaks. The cartilage-related markers were evaluated using Western blot and immunofluorescence. Additionally, a three-dimensional cell culture was used to determine the potential to form cartilage particles. RESULTS: iPSC-CM increased proliferation and diminished cell ROS production and senescence. CM influenced the cartilage-related protein expression and promoted the growth of cartilage particles. The cell exposed to CM did not lose the ECM proteins, suggesting the chondroprotective effect for prolonged culture time. CONCLUSION: Our preliminary results suggest a beneficial effect on maintaining chondrocyte biology during in vitro expansion.

3.
Molecules ; 29(4)2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38398556

RESUMEN

Lithium salt LiHDI (lithium 4,5-dicyano-2-(n-heptafluoropropyl)imidazolide) is proposed as a solid electrolyte interphase-stabilising additive for lithium-ion batteries, which can be added in a smaller amount than fluoroethylene carbonate (FEC) and vinylene carbonate (VC) additives. Electrolytes containing either lithium 4,5-dicyano-2-(trifluoromethyl)imidazolide (LiTDI) or battery-standard LiPF6 were tested with various amounts of LiHDI additive. Chemical stability in the presence of water and the thermal stability of LiHDI are on par with LiTDI. LiHDI additive does not negatively affect the properties of electrolytes. Conductivity measurements of solutions, galvanostatic cycling of graphite-LiFePO4 cells at room temperature, cells' cycling at 60 °C, internal cell resistance monitoring during cycling, and XPS analysis of electrodes' surfaces after cycling have been performed. LiHDI, unlike the FEC-VC mixture, does not negatively affect the properties of the electrolyte. Cycling showed improved capacity retention with LiHDI additive with both graphite and LiFePO4 as capacity-limiting electrodes over samples without additives. At elevated temperatures, samples with LiHDI exhibited better capacity retention during cycling than those with FEC-VC. Internal cell resistance can be correlated with capacity retention. XPS results show changes in the composition of SEI depending on the composition of the electrolyte and the duration of cycling.

4.
Int Orthop ; 46(3): 549-553, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34674021

RESUMEN

INTRODUCTION: Continuous passive motion (CPM) is a frequently used method in the early post-operative rehabilitation of patients after knee surgery. In this study, the effectiveness of the CPM method was evaluated after primary total knee arthroplasty during an early recovery period. METHODS: Eighty patients undergoing total knee arthroplasty were assigned into two groups. The experimental group received CPM and active exercises, while the control group active exercises only. All subjects were evaluated once before the surgery and at a discharge, in terms of mean active range of motion (AROM), mean Knee Society Score (KSS), and Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC). RESULTS: The mean AROM for the experimental group was 82.3° ± 14.3° and 76.1° ± 22.2° for the control. The mean KSS score was 136.4 ± 19.3 points for the experimental group, and 135.7 ± 15.1 for the control. There were no statistical differences between the two groups. The KSS functional score was 66.4 ± 8.1 points for the experimental group compared to 62.2 ± 7.3 points for the control, but there was a statistically significant difference between the groups at discharge from the hospital (p = 0.009). A subjective estimation of the pain level, joint stiffness and function also showed a statistically significant difference between the two groups (38.6 ± 14.3 points for the CPM group and 21.2 ± 15.7 for the control). CONCLUSION: These findings show that there is no significant effect of CPM in terms of improving clinical measurements. However, there was a significant beneficial effect on the subjective assessment of pain level, joint stiffness, and functional ability.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla , Artroplastia de Reemplazo de Rodilla/rehabilitación , Humanos , Articulación de la Rodilla/cirugía , Terapia Pasiva Continua de Movimiento/métodos , Osteoartritis de la Rodilla/cirugía , Rango del Movimiento Articular , Resultado del Tratamiento
5.
Int J Mol Sci ; 22(2)2021 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-33477381

RESUMEN

Nanoemulsion systems receive a significant amount of interest nowadays due to their promising potential in biomedicine and food technology. Using a two-step process, we produced a series of nanoemulsion systems with different concentrations of hemp seed oil (HSO) stabilized with Aesculus hippocastanum L. extract (AHE). Water and commercially-available low-concentrated hyaluronic acid (HA) were used as the liquid phase. Stability tests, including an emulsifying index (EI), and droplet size distribution tests performed by dynamic light scattering (DLS) proved the beneficial impact of AHE on the emulsion's stability. After 7 days of storage, the EI for the water-based system was found to be around 100%, unlike the HA systems. The highest stability was achieved by an emulsion containing 5% HSO and 2 g/L AHE in water, as well as the HA solution. In order to obtain the detailed characteristics of the emulsions, UV-Vis and FTIR spectra were recorded, and the viscosity of the samples was determined. Finally, a visible microscopic analysis was used for the homogeneity evaluation of the samples, and was compared with the DLS results of the water system emulsion, which showed a desirable stability. The presented results demonstrate the possible use of oil emulsions based on a plant extract rich in saponins, such as AHE. Furthermore, it was found that the anti-inflammatory properties of AHE provide opportunities for the development of new emulsion formulations with health benefits.


Asunto(s)
Aesculus/metabolismo , Cannabis/metabolismo , Emulsionantes/química , Dispersión Dinámica de Luz , Emulsiones/química , Nanopartículas/química , Tamaño de la Partícula , Aceites de Plantas/química , Semillas/metabolismo , Tensoactivos , Temperatura , Viscosidad , Agua
6.
Molecules ; 25(11)2020 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-32532010

RESUMEN

In this study, two saponins-rich plant extracts, viz. Saponaria officinalis and Quillaja saponaria, were used as surfactants in an oil-in-water (O/W) emulsion based on hempseed oil (HSO). This study focused on a low oil phase content of 2% v/v HSO to investigate stable emulsion systems under minimum oil phase conditions. Emulsion stability was characterized by the emulsification index (EI), centrifugation tests, droplet size distribution as well as microscopic imaging. The smallest droplets recorded by dynamic light scattering (droplets size v. number), one day after the preparation of the emulsion, were around 50-120 nm depending the on use of Saponaria and Quillaja as a surfactant and corresponding to critical micelle concentration (CMC) in the range 0-2 g/L. The surface and interfacial tension of the emulsion components were studied as well. The effect of emulsions on environmental bacteria strains was also investigated. It was observed that emulsions with Saponaria officinalis extract exhibited slight toxic activity (the cell metabolic activity reduced to 80%), in contrast to Quillaja emulsion, which induced Pseudomonas fluorescens ATCC 17400 growth. The highest-stability samples were those with doubled CMC concentration. The presented results demonstrate a possible use of oil emulsions based on plant extract rich in saponins for the food industry, biomedical and cosmetics applications, and nanoemulsion preparations.


Asunto(s)
Cannabis/química , Emulsiones , Extractos Vegetales/farmacología , Aceites de Plantas/química , Pseudomonas fluorescens/crecimiento & desarrollo , Rosaceae/química , Saponinas/farmacología , Pseudomonas fluorescens/efectos de los fármacos
7.
Int J Mol Sci ; 20(18)2019 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-31492046

RESUMEN

Human induced pluripotent stem cells (hiPSCs) play an important role in research regarding regenerative medicine. Particularly, chondrocytes differentiated from hiPSCs seems to be a promising solution for patients suffering from osteoarthritis. We decided to perform chondrogenesis in a three-week monolayer culture. Based on transcriptome analysis, hiPSC-derived chondrocytes (ChiPS) demonstrate the gene expression profile of cells from early chondrogenesis. Chondrogenic progenitors obtained by our group are characterized by significantly high expression of Hox genes, strongly upregulated during limb formation and morphogenesis. There are scanty literature data concerning the role of microRNAs in early chondrogenesis, especially in chondrogenic differentiation of hiPSCs. The main aim of this study was to investigate the microRNA expression profile and to select microRNAs (miRNAs) taking part in early chondrogenesis. Our findings allowed for selection crucial miRNAs engaged in both diminishing pluripotency state and chondrogenic process (inter alia hsa-miR-525-5p, hsa-miR-520c-3p, hsa-miR-628-3p, hsa-miR-196b-star, hsa-miR-629-star, hsa-miR-517b, has-miR-187). These miRNAs regulate early chondrogenic genes such as: HOXD10, HOXA11, RARB, SEMA3C. These results were confirmed by RT-qPCR analysis. This work contributes to a better understanding of the role of miRNAs directly involved in chondrogenic differentiation of hiPSCs. These data may result in the establishment of a more efficient protocol of obtaining chondrocyte-like cells from hiPSCs.


Asunto(s)
Condrogénesis/genética , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , MicroARNs/genética , Diferenciación Celular/genética , Células Cultivadas , Condrocitos/citología , Condrocitos/metabolismo , Biología Computacional/métodos , Perfilación de la Expresión Génica , Humanos , Transcriptoma
8.
Int J Mol Sci ; 20(11)2019 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-31159483

RESUMEN

The repair of damaged articular cartilage using currently available implantation techniques is not sufficient for the full recovery of patients. Pluripotent stem cells (iPSC)-based therapies could bring new perspectives in the treatment of joint diseases. A number of protocols of in vitro differentiation of iPSC in chondrocytes for regenerative purposes have been recently described. However, in order to use these cells in clinics, the elimination of animal serum and feeder cells is essential. In our study, a strictly defined and controllable protocol was designed for the differentiation of pluripotent stem cells (BG01V, ND 41658*H, GPCCi001-A) in chondrocyte-like cells in serum- and a feeder cell-free system, using the embryoid bodies step. The extension of the protocol and culture conditions (monolayer versus 3D culture) was also tested after the initial 21 days of chondrogenic differentiation. Promotion of the chondrogenic differentiation in 3D culture via the elevated expression of genes related to chondrogenesis was achieved. Using immunofluorescence and immunohistochemistry staining techniques, the increased deposition of the specific extracellular matrix was indicated. As a result, chondrocyte-like cells in the early stages of their differentiation using pellet culture under fully controlled and defined conditions were obtained.


Asunto(s)
Diferenciación Celular , Condrocitos/citología , Condrogénesis , Células Madre Pluripotentes/citología , Técnicas de Cultivo de Célula/métodos , Línea Celular , Cuerpos Embrioides/citología , Células Madre Embrionarias Humanas/citología , Humanos , Células Madre Pluripotentes Inducidas/citología
9.
Int J Mol Sci ; 19(2)2018 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-29439516

RESUMEN

Human induced pluripotent stem cells (hiPSCs) constitute an important breakthrough in regenerative medicine, particularly in orthopedics, where more effective treatments are urgently needed. Despite the promise of hiPSCs only limited data on in vitro chondrogenic differentiation of hiPSCs are available. Therefore, we compared the gene expression profile of pluripotent genes in hiPSC-derived chondrocytes (ChiPS) to that of an hiPSC cell line created by our group (GPCCi001-A). The results are shown on heatmaps and plots and confirmed by Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) analysis. Unlike the ChiPS, our GPCCi001-A cells maintained their pluripotency state during long-term culture, thus demonstrating that this cell line was comprised of stable, fully pluripotent hiPSCs. Moreover, these chondrocyte-like cells not only presented features that are characteristic of chondrocytes, but they also lost their pluripotency, which is an important advantage in favor of using this cell line in future clinical studies.


Asunto(s)
Condrocitos/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Diferenciación Celular , Células Cultivadas , Condrocitos/citología , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Humanos , Células Madre Pluripotentes Inducidas/citología
10.
Geophys Res Lett ; 44(3): 1554-1563, 2017 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-28344367

RESUMEN

Very sparse data have previously limited observational studies of meteorological processes in the Sahara. We present an observed case of convectively driven water vapor transport crossing the Sahara over 2.5 days in June 2012, from the Sahel in the south to the Atlas in the north. A daily cycle is observed, with deep convection in the evening generating moist cold pools that fed the next day's convection; the convection then generated new cold pools, providing a vertical recycling of moisture. Trajectories driven by analyses were able to capture the direction of the transport but not its full extent, particularly at night when cold pools are most active, and analyses missed much of the water content of cold pools. The results highlight the importance of cold pools for moisture transport, dust and clouds, and demonstrate the need to include these processes in models in order to improve the representation of Saharan atmosphere.

11.
Int Orthop ; 41(5): 983-989, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28013331

RESUMEN

PURPOSE: The study was designed to investigate whether serum concentrations of leptin, resistin and adiponectin in obese and normal-weight patients with primary knee osteoarthritis (OA) correlate with clinical and radiological stages of the disease and percentage of total body fat. METHODS: Seventy-three patients with knee OA, divided into obese and normal-weight groups, were clinically evaluated according to the Knee Society Score (KSS), and radiologically assessed using Kellgren and Lawrence scale. The percentage of total body fat and some anthropometric data were also given. Serum leptin, resistin and adiponectin concentrations were measured by Elisa and were correlated with the clinical, radiological and anthropometric parameters. RESULTS: Leptin concentrations were significantly higher (p = 0.001) in the obese patients and positively correlated (R = 0.63) with radiologically assessed OA grade, but only in the normal-weight group. Resistin and adiponectin concentrations were identical in obese and normal-weight patients and negatively correlated (R = -0.41) with the clinical status of obese patients. In both groups, percentage of total body fat positively correlated (R = 0.29 and R = 0.53 for obese and normal-weight respectively) with radiologically assessed OA grade. However, no correlations were found with clinical status of the patients. CONCLUSIONS: It was found that in the obese patients with knee OA, increased percentage of total body fat and elevated serum leptin concentration might favour the advancement of clinical but not radiologically assessed changes in the joint structures, while in normal-weight patients it correlates only with radiologically assessed changes but does not affect to an appreciable extent the clinical status of the patients.


Asunto(s)
Adiponectina/sangre , Tejido Adiposo/fisiopatología , Leptina/sangre , Obesidad/sangre , Osteoartritis de la Rodilla/sangre , Resistina/sangre , Anciano , Antropometría , Índice de Masa Corporal , Peso Corporal , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Articulación de la Rodilla/fisiopatología , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Osteoartritis de la Rodilla/complicaciones , Osteoartritis de la Rodilla/fisiopatología
12.
Postepy Hig Med Dosw (Online) ; 71(0): 500-509, 2017 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-28665279

RESUMEN

INTRODUCTION: Human articular cartilage has a poor regenerative capacity. This often results in the serious joint disease- osteoarthritis (OA) that is characterized by cartilage degradation. An inability to self-repair provided extensive studies on AC regeneration. The cell-based cartilage tissue engineering is a promising approach for cartilage regeneration. So far, numerous cell types have been reported to show chondrogenic potential, among others human embryonic stem cells (hESCs). MATERIALS AND METHODS: However, the currently used methods for directed differentiation of human ESCs into chondrocyte-like cells via embryoid body (EB) formation, micromass culture (MC) and pellet culture (PC) are not highly efficient and require further improvement. In the present study, these three methods for hESCs differentiation into chondrocyte-like cells in the presence of chondrogenic medium supplemented with diverse combination of growth factors (GFs) were evaluated and modified. RESULTS: The protocols established here allow highly efficient, simple and inexpensive production of a large number of chondrocyte-like cells suitable for transplantation into the sites of cartilage injury. The most crucial issue is the selection of appropriate GFs in defined concentration. The obtained stem-derived cells reveal the presence of chondrogenic markers such as type II collagen, Sox6 and Sox9 as well as the lack or significantly lower level of pluripotency markers including Nanog and Oct3/4. DISCUSSION: The most efficient method is the differentiation throughout embryoid bodies. In turn, chondrogenic differentiation via pellet culture is the most promising method for implementation on clinical scale. The most useful GFs are TGF-ß1, -3 and BMP-2 that possess the most chondrogenic potential. These methods can also be used to obtain chondrocyte-like cells from differentiating induced pluripotent stem cells (iPSCs).


Asunto(s)
Diferenciación Celular , Condrocitos , Células Madre Embrionarias Humanas/fisiología , Células Madre Pluripotentes Inducidas/fisiología , Ingeniería de Tejidos/métodos , Cartílago Articular/fisiología , Humanos , Regeneración , Medicina Regenerativa/métodos
13.
J Hum Genet ; 61(5): 457-61, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26763883

RESUMEN

Brachydactyly refers to shortening of digits due to hypoplasia or aplasia of bones forming the hands and/or feet. Isolated brachydactyly type E (BDE), which is characterized by shortened metacarpals and/or metatarsals, results in a small proportion of patients from HOXD13 or PTHLH mutations, although in the majority of cases molecular lesion remains unknown. BDE, like other brachydactylies, shows clinical heterogeneity with highly variable intrafamilial and interindividual expressivity. In this study, we investigated two Polish cases (one familial and one sporadic) presenting with BDE and additional symptoms due to novel PTHLH mutations. Apart from BDE, the affected family showed short stature, mild craniofacial dysmorphism and delayed bone age. Sanger sequencing of PTHLH revealed a novel heterozygous frameshift mutation c.258delC(p.N87Tfs*18) in two affected individuals and one relative manifesting mild brachydactyly. The sporadic patient, in addition to BDE, presented with craniofacial dysmorphism, normal stature and bone age, and was demonstrated to carry a de novo heterozygous c.166C>T(p.R56*) mutation. Our paper reports on the two novel truncating PTHLH variants, resulting in variable combination of BDE and other symptoms. Data shown here expand the knowledge on the phenotypic presentation of PTHLH mutations, highlighting significant clinical variability and incomplete penetrance of the PTHLH-related symptoms.


Asunto(s)
Braquidactilia/genética , Anomalías Craneofaciales/genética , Enanismo/genética , Heterocigoto , Mutación , Proteína Relacionada con la Hormona Paratiroidea/genética , Fenotipo , Adolescente , Huesos/diagnóstico por imagen , Huesos/patología , Braquidactilia/diagnóstico , Niño , Preescolar , Anomalías Craneofaciales/diagnóstico , Análisis Mutacional de ADN , Enanismo/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linaje , Síndrome
14.
Int Orthop ; 40(3): 615-24, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26762517

RESUMEN

Over 20 years ago it was realized that the traditional methods of the treatment of injuries to joint components: cartilage, menisci and ligaments, did not give satisfactory results and so there is a need of employing novel, more effective therapeutic techniques. Recent advances in molecular biology, biotechnology and polymer science have led to both the experimental and clinical application of various cell types, adapting their culture conditions in order to ensure a directed differentiation of the cells into a desired cell type, and employing non-toxic and non-immunogenic biomaterial in the treatment of knee joint injuries. In the present review the current state of knowledge regarding novel cell sources, in vitro conditions of cell culture and major important biomaterials, both natural and synthetic, used in cartilage, meniscus and ligament repair by tissue engineering techniques are described, and the assets and drawbacks of their clinical application are critically evaluated.


Asunto(s)
Materiales Biocompatibles/uso terapéutico , Traumatismos de la Rodilla/terapia , Procedimientos Ortopédicos/métodos , Ingeniería de Tejidos/métodos , Cartílago/citología , Técnicas de Cultivo de Célula/métodos , Humanos , Articulación de la Rodilla/cirugía , Ligamentos , Procedimientos Ortopédicos/efectos adversos , Polímeros
15.
Int Orthop ; 39(5): 995-1003, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25512139

RESUMEN

PURPOSE: The use of stem cells in regenerative medicine offers hope to treat numerous orthopaedic disorders, including articular cartilage defects. Although much research has been carried out on chondrogenesis, this complicated process is still not well understood and much more research is needed. The present review provides an overview of the stages of chondrogenesis and describes the effects of various growth factors, which act during the multiple steps involved in stem cell-directed differentiation towards chondrocytes. METHODS: The current literature on stem cell-directed chondrogenesis, in particular the role of members of the transforming growth factor-ß (TGF-ß) superfamily-TGF-ßs, bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs)-is reviewed and discussed. RESULTS: Numerous studies have reported the chondrogenic potential of both adult- and embryonic-like stem cells and the role of growth factors in programming differentiation of these cells towards chondrocytes. Mesenchymal stem cells (MSCs) are adult multipotent stem cells, whereas induced pluripotent stem cells (iPSC) are reprogrammed pluripotent cells. Although better understanding of the processes involved in the development of cartilage tissues is necessary, both cell types may be of value in the clinical treatment of cartilage injuries or osteoarthritic cartilage lesions. CONCLUSIONS: MSCs and iPSCs both present unique characteristics. However, at present, it is still unclear which cell type is most suitable in the treatment of cartilage injuries.


Asunto(s)
Cartílago Articular/lesiones , Cartílago Articular/fisiología , Condrogénesis , Células Madre Pluripotentes Inducidas/fisiología , Péptidos y Proteínas de Señalización Intercelular/fisiología , Regeneración/fisiología , Proteínas Morfogenéticas Óseas/farmacología , Cartílago Articular/metabolismo , Diferenciación Celular/fisiología , Condrocitos/metabolismo , Condrogénesis/fisiología , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Células Madre Mesenquimatosas/fisiología , Transducción de Señal/fisiología , Factor de Crecimiento Transformador beta/farmacología
16.
Int Orthop ; 39(6): 1211-7, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25716111

RESUMEN

Osteoarthritis (OA) is one of the most common causes of musculoskeletal disability in the world. Traditionally, it has been thought that obesity contributes to the development and progression of OA by increased mechanical load of the joint structures. Nevertheless, studies have shown that adipose tissue-derived cytokines (adipocytokines) are a possible link between obesity and OA. Furthermore, according to recent findings, not only articular cartilage may be the main target of these cytokines but also the synovial membrane, subchondral bone and infrapatellar fat pad may be encompassed in the process of degradation. This review presents the most recent reports on the contribution of adipocytokines to the knee joint cartilage degradation, osteophyte formation, infrapatellar fat pad alterations and synovitis.


Asunto(s)
Adipoquinas/fisiología , Osteoartritis de la Rodilla/fisiopatología , Adipoquinas/metabolismo , Huesos/patología , Cartílago Articular/patología , Citocinas/metabolismo , Progresión de la Enfermedad , Humanos , Articulación de la Rodilla/patología , Obesidad/epidemiología , Osteoartritis de la Rodilla/epidemiología , Osteoartritis de la Rodilla/metabolismo , Osteoartritis de la Rodilla/patología , Osteofito/patología , Factores de Riesgo , Membrana Sinovial/patología , Sinovitis/metabolismo
17.
Curr Genomics ; 15(6): 481-4, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25598697

RESUMEN

Multiple mechanisms are implicated in the development of primary osteoarthritis (OA), in which genetic and epigenetic factors appear to interact with environmental factors and age to initiate the disease and stimulate its progression. Changes in expression of microRNAs (miRs) contribute to development of osteoarthritis. Numerous miRs are involved in cartilage development, homeostasis and degradation through targeting genes expressed in this tissue. An important regulator of gene expression in human cartilage is miR-140, which directly targets a gene coding aggrecanase ADAMTS-5, that cleaves aggrecan in cartilage. This miR is considered a biological marker for cartilage and its level significantly decreases in OA cartilage. On the other hand, increased expression of miR-146a in early OA inhibits two other cartilage-degrading enzymes: MMP13 and ADAMTS4, and may provide a useful tool in developing treatments for OA. The COL2A1 gene, encoding collagen type II, which is the most abundant structural protein of the cartilage, is silenced by miR-34a and activated by miR-675. Every year, new targets of cartilage miRs are validated experimentally and this opens new possibilities for new therapies that control joint destruction and stimulate cartilage repair. At the same time development of next-generation sequencing technologies allows to identify new miRs involved in cartilage biology.

18.
BMC Med Genet ; 14: 13, 2013 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-23342975

RESUMEN

BACKGROUND: A partial duplication of the distal long arm of chromosome 5 (5q35-->qter) is known to be associated with a distinct phenotype referred to as Hunter-McAlpine syndrome. Clinical spectrum of this disorder mainly consists of mental retardation, microcephaly, short stature, skeletal anomalies, and craniofacial dysmorphism featuring flat facies, micrognathia, large, low-set dysplastic ears, hypertelorism, almond-shaped, down-slanted palpebral fissures, epicanthal folds, small nose, long philtrum, small mouth, and thin upper lip. Less frequent remarkable findings include craniosynostosis, heart defect, hypoplastic phalanges, preaxial polydactyly, hypospadias, cryptorchidism, and inguinal hernia. In most patients with a partial duplication of 5q the aberration occurred due to an inherited unbalanced translocation, therefore the phenotype was not reflective of pure trisomy 5q. CASE PRESENTATION: We report on a 9.5-year-old boy with some feature of Hunter-McAlpine syndrome including short stature, complex heart defect (dextrocardia, dextroversion, PFO), bilateral cryptorchidism, hypothyroidism, and craniofacial dysmorphism. Additionally, bilateral radial agenesis with complete absence of Ist digital rays, ulnar hypoplasia with bowing, choroidal and retinal coloboma, abnormal biliary vesicle were identified, which have never been noted in 5q trisomy patients. Karyotype analysis, sequencing and MLPA for TBX5 and SALL4 genes were unremarkable. Array comparative genomic hybridization detected a duplication on 5q35.2-5q35.3, resulting from a de novo chromosomal rearrangement. Our proband carried the smallest of all previously reported pure distal 5q trisomies encompassing terminal 5.4-5.6 Mb and presented with the most severe limb malformation attributed to the increased number of distal 5q copies. CONCLUSIONS: We postulate that a terminal distal trisomy of 5q35.2-5q35.3, which maps 1.1 Mb telomeric to the MSX2 gene is causative for both radial agenesis and complex heart defect in our proband. A potential candidate gene causative for limb malformation in our proband could be FGFR4, which maps relatively in the closest position to the chromosomal breakage site (about 1.3 Mb) from all known 5q duplications. Since the limb malformation as well as the underlying genetic defect are distinct from other 5q trisomy patient we propose that a position effect resulting in altered long-range regulation of the FGFR4 (alternatively MSX2) may be responsible for the limb malformation in our proband.


Asunto(s)
Síndrome del Maullido del Gato/genética , Cara/anomalías , Cardiopatías Congénitas/genética , Radio (Anatomía)/anomalías , Pulgar/anomalías , Trisomía/genética , Anomalías Múltiples/genética , Niño , Cromosomas Humanos Par 5/genética , Enanismo/genética , Humanos , Masculino
19.
Arch Orthop Trauma Surg ; 133(4): 541-9, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23371398

RESUMEN

BACKGROUND: Surgery of meniscus tear results in limitation of function. The aim of study was functional assessment of knee 1 year after surgery with two techniques in cases of the medial meniscus tear followed by the same supervised rehabilitation. MATERIALS AND METHODS: A total of 30 patients with good KOSS scores constituted two equal groups after partial meniscectomy or meniscus suture. Measurements of knee extensors and flexors muscles peak torques were performed with angular velocities 60, 180, 240 and 300 s(-1) using Biodex IV system. One-leg-hop and one-leg-rising tests ascertained the function of operated knee. Results of examinations were compared with reference to healthy volunteers. Results of biomechanical and clinical studies were correlated to create complex and objective method evaluating treatment. RESULTS: Extensors peak torque values at 60 s(-1) angular velocity and H/Q coefficient were decreased after meniscectomy more than meniscus suture in comparison to healthy volunteers (P ≤ 0.001; P ≤ 0.05). Analysis of functional tests revealed that patients after meniscectomy showed difference between operated and non-operated knee (P ≤ 0.01) while patients with meniscus suture differed the least to controls (P ≤ 0.05). Extensors peak torque values at 60 s(-1) angular velocity correlated with results of one-leg-rising test. CONCLUSION: Results suggest worse functional effects when meniscectomy is applied which implies modification of the rehabilitative methods in a postoperative period.


Asunto(s)
Traumatismos de la Rodilla/cirugía , Articulación de la Rodilla/cirugía , Meniscos Tibiales/cirugía , Técnicas de Sutura , Adulto , Fenómenos Biomecánicos , Femenino , Humanos , Traumatismos de la Rodilla/fisiopatología , Traumatismos de la Rodilla/rehabilitación , Articulación de la Rodilla/fisiopatología , Masculino , Meniscos Tibiales/fisiopatología , Recuperación de la Función , Reoperación , Suturas , Lesiones de Menisco Tibial , Adulto Joven
20.
Stem Cell Rev Rep ; 19(5): 1185-1213, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36790694

RESUMEN

BACKGROUND: The approaches currently used in osteoarthritis (OA) are mainly short-term solutions with unsatisfactory outcomes. Cell-based therapies are still controversial (in terms of the sources of cells and the results) and require strict culture protocol, quality control, and may have side-effects. A distinct population of stromal cells has an interesting secretome composition that is underrated and commonly ends up as biological waste. Their unique properties could be used to improve the existing techniques due to protective and anti-ageing properties. SCOPE OF REVIEW: In this review, we seek to outline the advantages of the use of conditioned media (CM) and exosomes, which render them superior to other cell-based methods, and to summarise current information on the composition of CM and their effect on chondrocytes. MAJOR CONCLUSIONS: CM are obtainable from a variety of mesenchymal stromal cell (MSC) sources, such as adipose tissue, bone marrow and umbilical cord, which is significant to their composition. The components present in CMs include proteins, cytokines, growth factors, chemokines, lipids and ncRNA with a variety of functions. In most in vitro and in vivo studies CM from MSCs had a beneficial effect in enhance processes associated with chondrocyte OA pathomechanism. GENERAL SIGNIFICANCE: This review summarises the information available in the literature on the function of components most commonly detected in MSC-conditioned media, as well as the effect of CM on OA chondrocytes in in vitro culture. It also highlights the need to standardise protocols for obtaining CM, and to conduct clinical trials to transfer the effects obtained in vitro to human subjects.


Asunto(s)
Células Madre Mesenquimatosas , Osteoartritis , Humanos , Medios de Cultivo Condicionados/farmacología , Medios de Cultivo Condicionados/metabolismo , Osteoartritis/terapia , Condrocitos , Citocinas/metabolismo
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