| 1. |
- Backesjo, CM, et al.
(author)
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Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells
- 2009
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In: Cells, tissues, organs. - : S. Karger AG. - 1422-6421 .- 1422-6405. ; 189:1-4, s. 93-97
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Journal article (peer-reviewed)abstract
- Mesenchymal stem cells (MSC) can differentiate into osteoblasts, adipocytes, chondrocytes and myoblasts. It has been suggested that a reciprocal relationship exists between the differentiation of MSC into osteoblasts and adipocytes. Peroxisome proliferator-activated receptor γ2 (PPARγ2) is a key element for the differentiation into adipocytes. Activation of the nuclear protein deacetylase Sirt1 has recently been shown to decrease adipocyte development from preadipocytes via inhibition of PPARγ2. In vitro, MSC differentiate to osteoblasts when exposed to bone-inducing medium. However, adipocytes are also developed. In the present study we have targeted Sirt1 to control adipocyte development during differentiation of MSC into osteoblasts. The finding that resveratrol and isonicotinamide markedly inhibited adipocyte and promoted osteoblast differentiation demonstrates an interesting alternative to PPARγ antagonists. These results are important for the evolving field of cell-based tissue engineering, but may also be relevant in the search for new treatments of osteoporosis.
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| 2. |
- Barreto Henriksson, Helena, et al.
(author)
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Development and Regeneration Potential of the Mammalian Intervertebral Disc
- 2013
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In: Cells Tissues and Organs. - : S. Karger AG. - 1422-6405 .- 1422-6421. ; 197:1
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Research review (peer-reviewed)abstract
- At the present time, the normal cell proliferation rate and regeneration processes in the intervertebral disc (IVD) are not fully known. Historically, the IVD has been considered an organ with little or no regenerative capacity. However, several studies have identified the presence of cells expressing progenitor/stem cell markers in adult cartilage tissue and recent data suggest that adult mammalian IVDs have regenerative capacity, albeit slow. The aim of this review is to give an overview of the present knowledge regarding IVD development, regeneration and repair mechanisms in mammals, with a special focus on human discs. At a time when regenerative medicine is making progress and biological treatment options, such as stem cell therapy, are suggested for patients with degenerated discs causing chronic low back pain, basic knowledge about disc cells and their regenerative capacity form a useful basis for the exploration of new treatment options.
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| 3. |
- Bloecker, K., et al.
(author)
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Morphometric Differences between the Medial and Lateral Meniscus in Healthy Men - A Three-Dimensional Analysis Using Magnetic Resonance Imaging
- 2012
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In: Cells Tissues Organs. - : S. Karger AG. - 1422-6405 .- 1422-6421. ; 195:4, s. 353-364
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Journal article (peer-reviewed)abstract
- The objective of this work was to characterize tibial plateau coverage and morphometric differences of the medial (MM) and lateral meniscus (LM) in a male reference cohort using three-dimensional imaging. Coronal multiplanar reconstructions of a sagittal double-echo steady state with water excitation magnetic resonance sequence (slice thickness: 1.5 mm, and in-plane resolution: 0.37 x 0.70 mm) were analyzed in 47 male participants without symptoms, signs or risk factors of knee osteoarthritis of the reference cohort of the Osteoarthritis Initiative. The medial and lateral tibial (LT) plateau cartilage area and the tibial, femoral and external surfaces of the MM and LM were manually segmented throughout the entire knee. This process was assisted by parallel inspection of a coronal intermediately weighted turbo spin echo sequence. Measures of tibial coverage, meniscus size, and meniscus position were computed three-dimensionally for the total menisci, the body, and the anterior and the posterior horn. The LM was found to cover a significantly greater (p < 0.001) proportion of the LT plateau (59 +/- 6.8%) than the MM of the medial plateau (50 +/- 5.5%). Whereas the volume of both menisci was similar (2.444 vs. 2.438 ml; p = 0.92), the LM displayed larger tibial and femoral surface areas (p < 0.05) and a smaller maximal (7.2 +/- 1.0 vs. 7.7 +/- 1.1 mm; p < 0.01) and mean thickness (2.7 +/- 0.3 vs. 2.8 +/- 0.3 mm; p < 0.001) than the medial one. Also, the LM displayed less (physiological) extrusion than the medial one. These data may guide strategies for meniscal tissue engineering and transplantation aiming to restore normal joint conditions. Copyright 2011 (C) S. Karger AG, Basel
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| 4. |
- Brisby, Helena, 1965, et al.
(author)
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Moderate Physical Exercise Results in Increased Cell Activity in Articular Cartilage of the Knee Joint in Rats.
- 2013
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In: Cells, tissues, organs. - : S. Karger AG. - 1422-6421 .- 1422-6405. ; 198:3, s. 237-248
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Journal article (peer-reviewed)abstract
- Background: Moderate exercise regimens have shown minor positive effects on matrix turnover in articular cartilage (AC), while effects at cellular level, e.g. proliferation, are scarcely described. Aim: The aim of this study was to investigate the effects of moderate exercise on cell proliferation and recruitment of cells possibly active in regeneration in different regions of cartilage in the rat knee joint. Methods: Eighteen rats were orally given 5-bromo-2-deoxyuridine (BrdU) for 14 days for in vivo DNA labeling. Nine rats underwent treadmill training for 50 min/day, 5 days/week (exercise group), and 9 rats served as controls (no exercise). Animals were sacrificed after 14, 56 and 105 days, and knee joints were harvested. BrdU+ cells were visualized immunohistochemically (IHC) and counted in AC, posterior stem cell niche (PN), potential migration route (PMR; area between PN and the AC border), potential migration area (PMA; region between PN and AC including PN) and epiphyseal cartilage plate (EP) of the tibia and femur. Results: Compared to controls, in the exercise group BrdU+ cells/mm(2) were increased on days 14 (p = 0.022) and 105 (p = 0.045) in AC of the tibia and on day 105 (p = 0.014) in AC of the femur. BrdU+ cell numbers were increased in the PMR region of the tibia on days 14 (p = 0.023) and 105 (p = 0.0018) and in the PMR region of the femur on day 105 (p = 0.0099) as well as in the PMA region of the tibia (p = 0.0008) and femur (p = 0.0080) on day 105. No significant differences in BrdU+ cells/mm(2) were seen in PN or EP between the groups at any time point. Regarding collagen 2A1 expression and proteoglycan accumulation, no significant differences between groups were detected. Conclusions: The results indicate increased cell activity in AC in response to physical exercise and may help to understand the complexity of AC regeneration in the normal mammal knee joint. © 2013 S. Karger AG, Basel.
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| 5. |
- Dare, Emma V., et al.
(author)
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Genipin Cross-Linked Fibrin Hydrogels for in vitro Human Articular Cartilage Tissue-Engineered Regeneration
- 2009
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In: Cells Tissues Organs. - : Karger. - 1422-6405 .- 1422-6421. ; 190:6, s. 313-325
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Journal article (peer-reviewed)abstract
- Our objective was to examine the potential of a genipin cross-linked human fibrin hydrogel system as a scaffold for articular cartilage tissue engineering. Human articular chondrocytes were incorporated into modified human fibrin gels and evaluated for mechanical properties, cell viability, gene expression, extracellular matrix production and subcutaneous biodegradation. Genipin, a naturally occurring compound used in the treatment of inflammation, was used as a cross-linker. Genipin cross-linking did not significantly affect cell viability, but significantly increased the dynamic compression and shear moduli of the hydrogel. The ratio of the change in collagen II versus collagen I expression increased more than 8-fold over 5 weeks as detected with real-time RT-PCR. Accumulation of collagen II and aggrecan in hydrogel extracellular matrix was observed after 5 weeks in cell culture. Overall, our results indicate that genipin appeared to inhibit the inflammatory reaction observed 3 weeks after subcutaneous implantation of the fibrin into rats. Therefore, genipin cross-linked fibrin hydrogels can be used as cell-compatible tissue engineering scaffolds for articular cartilage regeneration, for utility in autologous treatments that eliminate the risk of tissue rejection and viral infection.
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| 6. |
- Fossum, Magdalena, et al.
(author)
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Long-term culture of human urothelial cells : a qualitative analysis
- 2005
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In: Cells Tissues Organs. - : S. Karger AG. - 1422-6405 .- 1422-6421. ; 181:1, s. 11-22
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Journal article (peer-reviewed)abstract
- Today, in vitro culturing of autologous cells is an established method in the field of tissue reconstruction. It can be applied to urothelial cells and could have many clinical implications in urological reconstructive surgery. This development calls for quality controls concerning cells used for clinical treatment when cells are autotransplanted back to the patient. We have studied cultured cells in order to detect whether genetic or morphologic changes occur. Urothelial cells isolated from bladder lavage were cultured according to different protocols based on the presence or absence of feeder cells. Genetic studies were performed by means of karyotyping with standard G-banding and interphase fluorescent in situ hybridization (FISH) analyses. The morphology of these epithelial cells was judged as well as immunostaining for epithelial cell markers. In addition, to minimize the risk of feeder cell contamination, proliferation studies were performed on cultures including feeder cells that had been pretreated with different doses of mitomycin or radiation. In initial studies, when using feeder cells in each passage according to standard protocols, urothelial cells proliferated unfavourably after the fourth passage with increasing numbers of mouse cells as well as urothelial tetraploid cells. We could also show that urothelial cells from bladder lavage need feeder cells in order to establish primary cultures. Further propagation up to 14 passages was performed without feeder cells and the urothelial cells retained normal karyotypes. We also found that mitomycin treatment had its main effect on feeder cells during the first 2 h. When feeder cells were irradiated, 20 Gy was effective and no feeder cell contamination was seen. In conclusion, we found that a high standard of quality in urothelial cell culturing can be achieved with a careful culturing technique.
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| 7. |
- Gaida, James Edmund, et al.
(author)
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Evidence of the TNF-α system in the human Achilles tendon : expression of TNF-α and TNF receptor at both protein and mRNA levels in the tenocytes
- 2012
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In: Cells Tissues Organs. - : S. Karger. - 1422-6405 .- 1422-6421. ; 196:4, s. 339-352
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Journal article (peer-reviewed)abstract
- Understanding adaption to load is essential for prevention and treatment of tendinopathy/tendinosis. Cytokine release in response to load is one mechanism involved in mechanotransduction. The cytokine tumor necrosis factor alpha (TNF-α) is implicated in tendinosis and can induce apoptotic effects via tumor necrosis factor receptor 1 (TNFR1). The complete absence of information concerning the TNF-α system in Achilles tendon is a limitation as mid-portion Achilles tendinosis is very frequent. Purpose: To examine expression patterns of TNF-α and its two receptors (TNFR1 and TNFR2) in human Achilles tendinosis and control tissue and to biochemically confirm the presence of TNF-α in tendinosis tissue. Methods: TNF-α and TNFR1 mRNA were detected via in situ hybridization. TNF-α, TNFR1, and TNFR2 were demonstrated immunohistochemically. Apoptosis markers were utilized. ELISA was used to detect TNF-α. Results: TNF-α and TNFR1 mRNA was detected in tenocytes of both tendinosis and control tendons. Tenocytes from both groups displayed specific immunoreactions for TNF-α, TNFR1, and TNFR2. The widened/rounded tenocytes of tendinosis samples exhibited the most intense immunoreactions. Apoptosis was detected in only a subpopulation of the tenocytes in tendinosis tissue. TNF-α was measurable in tendinosis tissue. Inflammatory cells were not seen. Conclusion: This is the first evidence of the existence of the TNF-α system in the human Achilles tendon. Findings are confirmed at mRNA and protein levels as well as biochemically. The TNF-α system was in principle confined to the tenocytes. The connection between tenocyte morphology and the expression pattern of TNF-α, TNFR1, and TNFR2 suggests that the TNF-α system may be involved in tenocyte activation in Achilles tendinosis.
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| 8. |
- Gormus, U, et al.
(author)
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Comparative Proteome Analyses of Ureteropelvic Junction Obstruction and Surrounding Ureteral Tissue
- 2020
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In: Cells, tissues, organs. - : S. Karger AG. - 1422-6421 .- 1422-6405. ; 209:1, s. 2-12
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Journal article (peer-reviewed)abstract
- Ureteropelvic junction (UPJ) obstruction is a common problem in children, but its etiology remains unclear. In this study, the proteome profiles of the obstructed segment and its surrounding distal and proximal parts were comparatively evaluated. Twelve children younger than 2 years of age with unilateral intrinsic UPJ obstruction were included. The excised operational tissue was divided into three parts immediately after resection: the obstructed part (Obst), the distal normal ureteral part (Dist), and the proximal part of the obstructed segment (Prox). Proteins extracted from the tissue samples were subjected to two-dimensional gel electrophoresis analysis to identify differentially regulated proteins. Spot analysis revealed that four proteins, namely tropomyosin beta and alpha-1 chains, actin and desmin, were upregulated in Obst in comparison to Dist. A similar analysis between Obst and Prox showed that heat shock protein beta-1 and carbonic anhydrase-1 were upregulated in Obst, while tropomyosin alpha 3 chain and ATP synthase beta were upregulated in Prox. The last comparative analysis between Dist and Prox revealed upregulation of annexin-A5 and annexin-A1 in Dist and vimentin, mitochondrial ATP synthase subunit-beta, peroxiredoxin-2, and apolipoprotein-A1 in Prox. Bioinformatics analysis using the STRING server indicated that the differentially regulated proteins, altogether, point to the changes occurring in muscle filament sliding pathway. When regulations occurring in each group were mutually compared, a change in lipase inhibition activity was detected by STRING. This is the first study scrutinizing changes occurring in protein profiles in UPJ.
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| 9. |
- Gradin, P, et al.
(author)
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Transgenic overexpression of tartrate-resistant acid phosphatase is associated with induction of osteoblast gene expression and increased cortical bone mineral content and density
- 2012
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In: Cells, tissues, organs. - : S. Karger AG. - 1422-6421 .- 1422-6405. ; 196:1, s. 68-81
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Journal article (peer-reviewed)abstract
- Bone remodeling is a central event in the maintenance of skeletal tissue, and involves cycles of resorption followed by the formation of bone tissue. The activity of osteoclasts and osteoblasts during these cycles is tightly regulated by systemic and local factors coupling the action of these cells. Tartrate-resistant acid phosphatase (TRAP) is predominantly expressed in bone by osteoclasts but has also been detected in osteoblasts and osteocytes. Moreover, TRAP can stimulate the differentiation of mesenchymal lineage cells, i.e. progenitors of osteoblasts and adipocytes. In order to further explore the effects of TRAP on bone turnover, the structural and molecular phenotypes of osteoclasts and osteoblasts were assessed in TRAP-overexpressing transgenic mice. Transgenic mice of both sexes display increased cortical bone mineral content and density, which cannot be accounted for by decreased bone resorption since osteoclast numbers and resorptive activity do not differ from wild-type mice. Examination of the osteoblast phenotype revealed that markers of bone formation, i.e. procollagen type I N-terminal propeptides, and osteoblast lineage markers as well as the TRAP 1B mRNA transcript are increased in TRAP-overexpressing mice. Expression of the osteoclast-selective TRAP 1C mRNA is not increased in TRAP transgenic mice. Elevated expression of TRAP mRNA and protein were detected in osteoblasts, osteocytes and in the bone matrix of TRAP transgenic mice, suggesting that TRAP overexpression in osteoblast lineage cells is associated with increased cortical bone mineral content and density. The data presented here support the hypothesis that TRAP overexpression in the osteoblastic cell lineage stimulates the differentiation and/or activation of these cells.
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| 10. |
- Granberg, I, et al.
(author)
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Capillary supply in relation to myosin heavy chain fibre composition of human intrinsic tongue muscles
- 2010
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In: Cells Tissues Organs. - : S. Karger AG. - 1422-6405 .- 1422-6421. ; 192:5, s. 303-313
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Journal article (peer-reviewed)abstract
- The capillary supply and myosin heavy chain (MyHC) composition of three different intrinsic tongue muscles was analysed in the anterior and posterior regions of the human tongue with biochemical and immunohistochemical techniques. Mean capillary density for the whole tongue was 796 ± 82 cap/mm², without regional differences. The overall number of capillaries around each fibre (CAF) was higher in the posterior than in the anterior region (2.5 vs. 2.1, p = 0.009). However, correcting for regional differences in fibre size, CAF per fibre area was higher in the anterior region (4.3 vs. 3.0, p < 0.001). Muscle fibres containing fast MyHCs predominated in the anterior region (78.7%), consisting of MyHCIIa (58.5%), MyHCIIx (1.0%), MyHCIIa+MyHCIIx (11.3%) and MyHCI+MyHCIIa (7.9%). Fibres containing slow MyHC predominated in the posterior region (65.2%), consisting of MyHCI (45.5%) and MyHCI+MyHCIIa (19.7%). A minor fibre population (<2%) contained unusual MyHC isoforms, namely MyHC foetal, MyHC slow-tonic, MyHC α-cardiac or MyHC embryonic. The microvascularization of the human tongue was twice as high as in human limb muscles. Regional similarities in capillary supply, but differences in fibre phenotype composition, suggest that human tongue muscle fibres are fatigue resistant independently of MyHC content. High frequency of hybrid fibres, that is fibres co-expressing two or more MyHC isoforms, indicates a wider spectrum of fibre contractile properties than in limb muscles. In conclusion, human intrinsic tongue muscles showed internal specialization in distribution of MyHC isoforms and capillary supply, but not in the expression of unusual MyHCs.
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