| 1. |
- Arvidson, K., et al.
(författare)
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Bone regeneration and stem cells
- 2011
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Ingår i: Journal of Cellular and Molecular Medicine (Print). - : Wiley-Blackwell. - 1582-1838 .- 1582-4934. ; 15:4, s. 718-746
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Forskningsöversikt (refereegranskat)abstract
- Introduction Bone fracture healing and healing problems Biomaterial scaffolds and tissue engineering in bone formation Bone tissue engineering Biomaterial scaffolds Synthetic scaffolds Micro- and nanostructural properties of scaffolds Conclusion Mesenchymal stem cells and osteogenesis Bone tissue Origin of osteoblasts Isolation and characterization of bone marrow derived MSC In vitro differentiation of MSC into osteoblast lineage cells In vivo differentiation of MSC into bone Factors and pathways controlling osteoblast differentiation of hMSC Defining the relationship between osteoblast and adipocyte differentiation from MSC MSC and sex hormones Effect of aging on osteoblastogenesis Conclusion Embryonic, foetal and adult stem cells in osteogenesis Cell-based therapies for bone Specific features of bone cells needed to be advantageous for clinical use Development of therapeutic biological agents Clinical application concerns Conclusion Platelet-rich plasma (PRP), growth factors and osteogenesis PRP effects in vitro on the cells involved in bone repair PRP effects on osteoblasts PRP effects on osteoclasts PRP effects on endothelial cells PRP effects in vivo on experimental animals The clinical use of PRP for bone repair Non-union Distraction osteogenesis Spinal fusion Foot and ankle surgery Total knee arthroplasty Odontostomatology and maxillofacial surgery Conclusion Molecular control of osteogenesis TGF-beta signalling FGF signalling IGF signalling PDGF signalling MAPK signalling pathway Wnt signalling pathway Hedgehog signalling Notch signalling Ephrin signalling Transcription factors regulating osteoblast differentiation Conclusion Summary This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed.
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| 2. |
- Kouri, V. P., et al.
(författare)
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Neutrophils produce interleukin-17B in rheumatoid synovial tissue
- 2014
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 53:1, s. 39-47
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Tidskriftsartikel (refereegranskat)abstract
- Objective: T helper 17 (Th17) and mast cells produce IL-17A in RA and critically contribute to the pathogenesis of RA. However, the complete IL-17 cytokine profile in RA is unknown. The aim of the study was to systematically study the expression of IL-17 family cytokines in RA. Methods: The expression of all IL-17 cytokines in RA synovium and pannus as well as in the synovium of OA was determined using quantitative RT-PCR (qRT-PCR). IL-17A and IL-17B were immunostained. Peripheral blood neutrophils were analysed for IL-17B. The effect of IL-17B alone or in combination with TNF-α was tested in vitro on fibroblasts and endothelial cells. Results: In all tissues IL-17B was the most expressed IL-17 family cytokine, found in lining but most strongly expressed in human neutrophil elastase containing polymorphonuclear cells. This pattern was distinct from that of IL-17A, which was found in mast cell tryptase immunoreactive cells. Circulating neutrophils contained IL-17B, verifying the in vivo results. Fibroblasts up-regulated the expression of IL-17RB, a putative receptor of IL-17B, after TNF-α stimulation. IL-17B significantly enhanced TNF-α-induced production of G-CSF and IL-6 in fibroblasts. Conclusion: IL-17B, which is present in synovium, may contribute to the pathogenesis of RA. IL-17B can enhance the effects of TNF-α on the production of cytokines and chemokines that control immune cell trafficking and neutrophil homeostasis in the inflamed tissues. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
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| 3. |
- van Osch, G. J., et al.
(författare)
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Cartilage repair: past and future--lessons for regenerative medicine
- 2009
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Ingår i: Journal of Cellular and Molecular Medicine. - 1582-4934. ; 13:5, s. 792-810
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Tidskriftsartikel (refereegranskat)abstract
- Since the first cell therapeutic study to repair articular cartilage defects in the knee in 1994, several clinical studies have been reported. An overview of the results of clinical studies did not conclusively show improvement over conventional methods, mainly because few studies reach level I of evidence for effects on middle or long term. However, these explorative trials have provided valuable information about study design, mechanisms of repair and clinical outcome and have revealed that much is still unknown and further improvements are required. Furthermore, cellular and molecular studies using new technologies such as cell tracking, gene arrays and proteomics have provided more insight in the cell biology and mechanisms of joint surface regeneration. Besides articular cartilage, cartilage of other anatomical locations as well as progenitor cells are now considered as alternative cell sources. Growth Factor research has revealed some information on optimal conditions to support cartilage repair. Thus, there is hope for improvement. In order to obtain more robust and reproducible results, more detailed information is needed on many aspects including the fate of the cells, choice of cell type and culture parameters. As for the clinical aspects, it becomes clear that careful selection of patient groups is an important input parameter that should be optimized for each application. In addition, the study outcome parameters should be improved. Although reduced pain and improved function are, from the patient's perspective, the most important outcomes, there is a need for more structure/tissue-related outcome measures. Ideally, criteria and/or markers to identify patients at risk and responders to treatment are the ultimate goal for these more sophisticated regenerative approaches in joint surface repair in particular, and regenerative medicine in general.
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| 4. |
- Vasara, Anna I, et al.
(författare)
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Subchondral bone reaction associated with chondral defect and attempted cartilage repair in goats.
- 2004
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 74:1, s. 107-14
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Tidskriftsartikel (refereegranskat)abstract
- Repair of cartilage damage with autologous chondrocyte transplantation (ACT) has become popular in clinical use during the past few years. Although clinical results have mostly been successful, several unanswered questions remain regarding the biological mechanism of the repair process. The aim of this study was to develop a goat model for ACT. The repair was not successful due to the graft delamination, but we characterize the subchondral changes seen after the procedure. A chondral lesion was created in 14 goat knees, operated on 1 month later with ACT, and covered with periosteum or a bioabsorbable poly-L/D-lactide scaffold. After 3 months, only two of the five lesions repaired with ACT showed partly hyaline-like repair tissue, and all lesions (n = 4) with the scaffold failed. Even though the lesions did not extend through the calcified cartilage, the bone volume and collagen organization of bone structure were decreased when assessed by quantitative polarized light microscopy. There was a significant loss of bone matrix and distortion of the trabecular structure of subchondral bone, which extended several millimeters into the bone. The subchondral bone demonstrated strong hyaluronan staining in the bone marrow and cartilaginous areas with signs of endochondral ossification, suggesting structural remodeling of the bone. The goat model used here proved not to be an optimal model for ACT. The changes in subchondral bone may alter the biomechanical properties of the subchondral plate and thus the long-term survival of the repair tissue after ACT.
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| 5. |
- Virtanen, Ismo, et al.
(författare)
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Blood vessels of human islets of Langerhans are surrounded by a double basement membrane
- 2008
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:7, s. 1181-91
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Based on mouse study findings, pancreatic islet cells are supposed to lack basement membrane (BM) and interact directly with vascular endothelial BM. Until now, the BM composition of human islets has remained elusive. METHODS: Immunohistochemistry with specific monoclonal and polyclonal antibodies as well as electron microscopy were used to study BM organisation and composition in human adult islets. Isolated islet cells and function-blocking monoclonal antibodies and recombinant soluble Lutheran peptide were further used to study islet cell adhesion to laminin (Lm)-511. Short-term cultures of islets were used to study Lutheran and integrin distribution. RESULTS: Immunohistochemistry revealed a unique organisation for human Lm-511/521 as a peri-islet BM, which co-invaginated into islets with vessels, forming an outer endocrine BM of the intra-islet vascular channels, and was distinct from the vascular BM that additionally contained Lm-411/421. These findings were verified by electron microscopy. Lutheran glycoprotein, a receptor for the Lm alpha5 chain, was found prominently on endocrine cells, as identified by immunohistochemistry and RT-PCR, whereas alpha(3) and beta(1) integrins were more diffusely distributed. High Lutheran content was also found on endocrine cell membranes in short-term culture of human islets. The adhesion of dispersed beta cells to Lm-511 was inhibited equally effectively by antibodies to integrin and alpha(3) and beta(1) subunits, and by soluble Lutheran peptide. CONCLUSIONS/INTERPRETATION: The present results disclose a hitherto unrecognised BM organisation and adhesion mechanisms in human pancreatic islets as distinct from mouse islets.
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| 7. |
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| 8. |
- Mackiewicz, Z, et al.
(författare)
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Receptor activator of nuclear factor kappa B ligand in an experimental intervertebral disc degeneration.
- 2009
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Ingår i: Clinical and experimental rheumatology. - 0392-856X. ; 27:2, s. 299-306
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Tidskriftsartikel (refereegranskat)abstract
- This study was designed to clarify the role of the receptor activator of nuclear factor kappa B ligand (RANKL) in the process of discus degeneration and spondylarthrosis. It was hypothesized that experimental discus lesion would initiate not only local bone remodelling but also increased osteoclast formation on a location remote to the injury site due to altered spinal biomechanics. It was speculated that these changes in vertebral bone remodelling could be reflected in an increased RANKL expression.
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| 9. |
- Pöllänen, E., et al.
(författare)
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Differential influence of peripheral and systemic sex steroids on skeletal muscle quality in pre- and postmenopausal women
- 2011
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Ingår i: Aging Cell. - : Wiley. - 1474-9718. ; 10:4, s. 650-660
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Tidskriftsartikel (refereegranskat)abstract
- Aging is associated with gradual decline of skeletal muscle strength and mass often leading to diminished muscle quality. This phenomenon is known as sarcopenia and affects about 30% of the over 60-year-old population. Androgens act as anabolic agents regulating muscle mass and improving muscle performance. The role of female sex steroids as well as the ability of skeletal muscle tissue to locally produce sex steroids has been less extensively studied. We show that despite the extensive systemic deficit of sex steroid hormones in postmenopausal compared to premenopausal women, the hormone content of skeletal muscle does not follow the same trend. In contrast to the systemic levels, muscle tissue of post- and premenopausal women had similar concentrations of dehydroepiandrosterone and androstenedione, while the concentrations of estradiol and testosterone were significantly higher in muscle of the postmenopausal women. The presence of steroidogenetic enzymes in muscle tissue indicates that the elevated postmenopausal steroid levels in skeletal muscle are because of local steroidogenesis. The circulating sex steroids were associated with better muscle quality while the muscle concentrations reflected the amount of infiltrated fat within muscle tissue. We conclude that systemically delivered and peripherally produced sex steroids have distinct roles in the regulation of neuromuscular characteristics during aging.
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| 10. |
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| 11. |
- Trokovic, N., et al.
(författare)
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Exosomal secretion of death bullets: a new way of apoptotic escape?
- 2012
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Ingår i: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 303:8
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Tidskriftsartikel (refereegranskat)abstract
- Trokovic N, Pollanen R, Porola P, Stegaev V, Hetzel U, Tivesten A, Engdahl C, Carlsten H, Forsblad-D'Elia H, Fagman JB, Lagerquist M, Konttinen YT. Exosomal secretion of death bullets: a new way of apoptotic escape? Am J Physiol Endocrinol Metab 303: E1015-E1024, 2012. First published August 12, 2012; doi: 10.1152/ajpendo.00139.2012.-Ovariectomy/estrogen deficiency causes selective apoptosis of the serous epithelial cells of the submandibular glands (SMG) in female mice. Because such apoptosis does not occur in healthy, estrogen-deficient male mice, it was hypothesized that dihydrotestosterone (DHT) protects epithelial SMG cells against apoptosis. The antiapoptotic effect of DHT on human epithelial HSG cells exposed to tumor necrosis factor-alpha and cycloheximide was studied. Correspondingly, the proapoptotic effect of androgen deficiency was studied in orchiectomized (ORX) androgen-knockout (ARKO) and wild-type (WT) mice. The health state of the SMG cells was studied with Alcian blue-periodic acid Schiff (AB-PAS) and amylase staining and transmission electron microscopy (TEM). The eventual protective antiapoptotic effect of dehydroepiandrosterone (DHEA) treatment was tested in this model. Apoptosis was assessed using immunohistochemisty of cleaved effector caspase-3 and its activator caspase-8 and the TUNEL assay. To test for the bioavailability, intracrine metabolism and sex steroid effects of DHEA, cystein-rich secretory protein-3 (CRISP-3), and leucine-isoleucine-valine transport system 1 (LIV-1) were used as androgen-and estrogen-regulated biomarkers, respectively. DHT protected HSG cells against induced apoptosis. In mice, androgen deficiency resulted in extensive activation of apoptotic caspase-8/3 cascade in serous epithelial cells. However, in salivary glands, active caspases were not translocated to nuclei but secreted to salivary ducts in exosome-like particles, which are associated with weak AB-PAS and amylase staining of the androgen-deprived cells and reduced number of intracellular secretory granules. DHEA treatment suppressed induction of proapoptotic caspases and almost normalized mucins and amylase and ultramophology of the serous epithelial cells in WT ORX but not ARKO ORX mice. According to the CRISP-3 and LIV-1 markers, DHEA probably exerted its effects via intracrine conversion to DHT.
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