| 1. |
- Arokoski, Jari, et al.
(författare)
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Nivelrikon etiopatogeneesi [Etiopathogenesis of osteoarthritis].
- 2001
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Ingår i: Duodecim. - : Duodecim. - 0012-7183 .- 2242-3281. ; 117:16, s. 1617-1626
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Tidskriftsartikel (refereegranskat)abstract
- Nivelrikon patofysiologia tunnetaan huonosti. Nykykäsityksen mukaan artroosissa ei olekyse nivelruston passiivisesta kulumisesta vaan biokemiallisesta tapahtumasarjasta, jossasoluväliaineen tuhoutuminen saa ylivallan rustoa korjaavista prosesseista. Nivelrikon alkuvaiheessarustosoluissa eli kondrosyyteissä aktivoituvat sekä ruston aineosien synteesitoimintaettä rustoa hajottavien entsyymien ilmentyminen ja niitä koodaavien geenientoiminta. Nivelrikko on koko nivelen sairaus, joka aiheuttaa muutoksia niin nivelrustossa,luussa kuin pehmytosissakin. Vallitsevan käsityksen mukaan nivelrikko käynnistyynivelruston pinnallisesta vyöhykkeestä. On myös esitetty, että nivelalueen altistuminenliialliselle kuormitukselle aiheuttaisi ensin rustonalaisen luun paksunemisen ja jäykkenemisen,mikä puolestaan altistaisi nivelruston suuremmille kuormittaville voimille. Riskitekijöistätärkeimpiä ovat ikääntyminen, liikapaino, niveleen kohdistuvat vammat ja ruumiillisentyön aiheuttama liikarasitus. Perinnöllisten tekijöiden osuus on myös merkittävä.Ruston kollageenien rakennevirheiden tiedetään altistavan nivelrikolle.
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| 2. |
- Elo, Mika, et al.
(författare)
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Differential regulation of stress proteins by high hydrostatic pressure, heat shock, and unbalanced calcium homeostasis in chondrocytic cells.
- 2000
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Ingår i: Journal of Cellular Biochemistry. - : John Wiley & Sons. - 0730-2312 .- 1097-4644. ; 79:4, s. 610-619
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Tidskriftsartikel (refereegranskat)abstract
- High hydrostatic pressure (HP) has recently been shown to increase cellular heat shock protein 70 (Hsp70) level in a specific way that does not involve transcriptional activation of the gene, but rather the stabilisation of the mRNA for Hsp70. In this study, we investigated whether there are other observable changes caused by HP stress, and compared them with those induced by certain other forms of stressors. A chondrocytic cell line T/C28a4 was exposed to 30 MPa continuous HP, heat shock at 43 degrees C, and increased cytosolic calcium concentration by the addition of sarco-endoplasmic reticulum Ca(2+) ATPase inhibitor thapsigargin (25 nM) or calcium ionophore A23187 (1 microM) in the cultures. The protein synthesis was studied by in vitro metabolic labelling followed by one- and two-dimensional polyacrylamide gel electrophoresis, and mass spectrometry was utilized to confirm the identity of the protein spots on two-dimensional gels. Continuous 30 MPa HP increased remarkably the relative labelling of Hsp70. Labelling of Hsp90 was also increased by 15-20%, although no clear change was evident at the protein level in Western blots. Elevated intracellular Ca(2+) concentration induced by thapsigargin and calcium ionophore A23187 increased mainly the synthesis of glucose-regulated protein 78 (Grp78/BiP), whereas Hsp70 and Hsp90 were decreased by the treatment. Heat shock was the strongest inducer of Hsp70 and Hsp90. This study further confirmed the induction of Hsp70 in chondrocytic cells exposed to high HP, but it also showed that calcium-mediated responses are unlikely to cause the stress response observed in the hydrostatically pressurized cells.
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| 3. |
- Elo, Mika, et al.
(författare)
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Specific induction of heat shock protein 90beta by high hydrostatic pressure.
- 2003
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Ingår i: Biorheology. - : IOS Press. - 0006-355X .- 1878-5034. ; 40:1-3, s. 141-146
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Tidskriftsartikel (refereegranskat)abstract
- In chondrocytes, a low-amplitude intermittent hydrostatic pressure induces production of extracellular matrix molecules, while high hydrostatic pressure inhibits it. High pressure increases cellular heat shock protein 70 level in a number of cell types on account of increased stabilisation of the heat shock protein 70 mRNA. In our experiments, only bovine primary chondrocytes, but not an immortalized chondrocytic cell line, could resist the induction of the stress response in the presence of continuous 30 MPa hydrostatic pressure. We have recently shown that protein synthesis is required for the stabilization. According to two-dimensional gel electrophoresis the synthesis of heat shock protein 90 was also increased in a chondrocytic cell line and in HeLa cells, and mass spectrometric analysis suggested that the induction was rather due to increase in heat shock protein 90beta than in heat shock protein 90alpha. The stress response was rather intense in HeLa cells, therefore, we investigated the effect of continuous 30 MPa hydrostatic pressure on the expression of the two heat shock protein 90 genes in HeLa cells using Northern and Western blot analyses. Heat shock protein 90beta mRNA level increased within 6 hours of exposure to 30 MPa hydrostatic pressure, while hsp90alpha level remained stable. At protein level there was a clear increase in the heat shock protein 90beta/heat shock protein 90alpha ratio, too. These results show a specific regulation of stress proteins in cells exposed to high hydrostatic pressure.
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| 4. |
- Espanha, Maria, et al.
(författare)
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Extracellular matrix composition of full-thickness defect repair tissue is little influenced by exercise in rat articular cartilage.
- 2001
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Ingår i: Connective Tissue Research. - 0300-8207 .- 1607-8438. ; 42:2, s. 97-109
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Tidskriftsartikel (refereegranskat)abstract
- Full-thickness articular cartilage defects in the femoral condyles of adult rats were examined four and eight weeks after injury. Quantitative polarized light microscopic analysis showed that birefringence of the tissue in the central repair area increased more in rats exercised on a treadmill. Glycosaminoglycan content in the repair tissue was also higher than in the intermittent active motion group at four weeks after injury, but by eight weeks the levels were similar in both groups. No normal-looking articular cartilage was formed in the lesions, and only in one animal type II collagen was observed in the superficial zone of repair tissue. No 3B3(-) antigenicity of the proteoglycans was seen during repair. In conclusion, exercise minimally modified the repair of full-thickness articular cartilage defects in adult rats. The repair in the exercised group may occur slightly faster in the early stages but no difference was seen at the eight week time interval between the exercised and the intermittently active group.
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| 5. |
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| 6. |
- Hyttinen, Mika, et al.
(författare)
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Age matters : collagen birefringence of superficial articular cartilage is increased in young guinea-pigs but decreased in older animals after identical physiological type of joint loading.
- 2001
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Ingår i: Osteoarthritis and Cartilage. - : Saunders Elsevier. - 1063-4584 .- 1522-9653. ; 9:8, s. 694-701
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare responses of the collagen network and glycosaminoglycans (GAGs) of articular cartilage to physiological type of joint loading in young growing and adult mature guinea-pigs.DESIGN: 10- and 44-week-old guinea-pigs were accustomed to treadmill running for 3 weeks. Thereafter the animals ran 2500 m/day, 5 days a week, for 15 weeks. Articular cartilage specimens from knee joints were collected at 28 and 62 weeks. Osteoarthritis (OA) prevalence and severity was evaluated by aid of light microscopy. The degree of collagen fibril network organization and content was analyzed with quantitative polarized light microscopy. The local concentration of GAGs was determined from cartilage sections with digital densitometry after safranin-O staining.RESULTS: In the young guinea-pigs, running increased up to 24% the optical retardation of polarized light by collagen in the superficial articular cartilage of femur, indicating either a higher degree of fibril assembly and organization or increased amount of collagen, or both. In contrast, in the adult mature animals the optical retardation decreased almost 50% after joint loading (P< 0.01-0.001). Running did not increase cartilage fibrillation. Significant changes in GAG content of cartilage were not found either in the young or adult mature runners.CONCLUSIONS: Increased birefringence of the superficial articular cartilage after joint loading in young guinea-pigs can be interpreted to be a sign of improved and decreased birefringence in older animals a sign of worsened property of the collagen network. It can be suggested therefore that joint loading strengthened the collagen network in the young runners. It can be hypothesized further that with time the inferior property of the collagen network predisposes the older runners to earlier OA than in controls.
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| 7. |
- Kaarniranta, Kai, et al.
(författare)
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Neuronal cells show regulatory differences in the hsp70 gene response.
- 2002
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Ingår i: Brain Research. Molecular Brain Research. - : Elsevier. - 0169-328X .- 1872-6941. ; 101:1-2, s. 136-140
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis of heat shock proteins (Hsps), encoded by heat shock genes, is increased in response to various stress stimuli. Hsps function as molecular chaperones, they dissociate cytotoxic stress-induced protein aggregates within cells and ensure improved survival. Induction of heat shock genes is mainly regulated at the transcriptional level. The stress responsive transcription factor, heat shock factor 1 (HSF1), is involved in the transcriptional induction of the heat shock genes. Our objective was to examine how hsp70 genes are regulated in different transformed and primary neurons upon exposure to elevated temperature. Our findings reveal that the Hsp70 response is regulated at the translational level in Neuro-2a neuroblastoma cells, while the IMR-32 neuroblastoma cells respond to stress by the classical HSF1-driven transcriptional regulatory mechanism. Primary rat hippocampal neurons show a lack of HSF1 and induction of the hsp70 gene. These observations suggest that neuronal cells display different hsp70 gene expression patterns which range from undetected response to transcriptional and posttranscriptional regulation during heat stress.
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| 8. |
- Kaarniranta, Kai, et al.
(författare)
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Primary chondrocytes resist hydrostatic pressure-induced stress while primary synovial cells and fibroblasts show modified Hsp70 response.
- 2001
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Ingår i: Osteoarthritis and Cartilage. - : Saunders Elsevier. - 1063-4584 .- 1522-9653. ; 9:1, s. 7-13
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: During joint loading, chondrocytes in the articular cartilage are subjected to gradients of high compressive hydrostatic pressure (HP). In response to diverse chemical or physical stresses, heat shock genes are induced to express heat shock proteins (Hsps). This study sought to examine the role of Hsps in baroresistance in primary bovine chondrocytes and synovial cells, as well as in primary human fibroblasts.METHODS: Northern blotting was used to analyze the steady-state levels of hsp70 mRNA in the primary cells exposed to HP or heat stress. Hsp70 protein accumulation was analyzed by Western blotting, and the DNA-binding activity was examined by gel mobility shift assay.RESULTS: Primary bovine chondrocytes which have been adapted to live under pressurized conditions showed negligible Hsp70 response upon HP loading, whereas primary bovine synovial cells and human fibroblasts accumulated hsp70 mRNA and protein when subjected to HP. The response was initiated without activation of the heat shock transcription factor 1. Interestingly, pre-conditioning of the barosensitive fibroblasts with HP or heat shock reduced the Hsp70 response, indicating induction of baroresistance.CONCLUSION: This study suggests that Hsp70 can play an important role in the early stages of adaptation of cells to HP. Thus, the Hsp70 gene expression upon HP loading may serve as one indicator of the chondrocytic phenotype of the cells. This can be of use in the treatment of cartilage lesions.
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| 9. |
- Kaarniranta, Kai, et al.
(författare)
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Protein synthesis is required for stabilization of hsp70 mRNA upon exposure to both hydrostatic pressurization and elevated temperature.
- 2000
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Ingår i: FEBS Letters. - : Elsevier. - 0014-5793 .- 1873-3468. ; 475:3, s. 283-286
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Tidskriftsartikel (refereegranskat)abstract
- We have recently described that in chondrocytic cells high hydrostatic pressure (HP) causes a heat shock response via mRNA stabilization without a transcriptional activation of the hsp70 gene. In this study, we investigated whether this exceptional regulatory mechanism occurs more generally in different types of cells. Indeed, hsp70 mRNA and protein accumulated in HeLa, HaCat and MG-63 cells under 30 MPa HP, without DNA-binding of heat shock transcription factor 1 (HSF1) to the heat shock element of the hsp70 gene or formation of nuclear HSF1 granules, revealing a lack of transcriptional activation. Moreover, we observed that protein synthesis is needed for mRNA stabilization. Thus, high HP offers a model to study the mechanisms of hsp70 mRNA stabilization without HSF1-mediated induction of the heat shock gene response.
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| 10. |
- Kaarniranta, Kai, et al.
(författare)
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Solustressin tutkimuksesta kliinisiin läpimurtoihin? [From research of cellular stress to various clinical break through innovations?]
- 2001
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Ingår i: Duodecim. - : Duodecim. - 0012-7183 .- 2242-3281. ; 117:22, s. 2266-2272
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Forskningsöversikt (refereegranskat)abstract
- Fysikaalisen tai kemiallisen stressin seurauksena useiden geenien aktiivisuus vähenee,kun taas lämpösokki- eli stressigeenien induktio lisääntyy. Stressigeenit koodaavat lämpösokkiproteiineja(Hsp), jotka toimivat soluissa kaperoneina, »avustajina», auttaensolujen proteiineja laskostumaan oikein translaatiossa, kalvon läpi kuljetuksessa tai esimerkiksikorkean lämpötilan aiheuttaman vaurion jälkeen. Viime vuosina lämpösokkiproteiinienkliininen merkitys useiden sairauksien patogeneesissä, diagnostiikassa ja ennusteenmäärittämisessä on alkanut selvitä. Merkittävimmät kliiniset löydökset liittyvätiskeemisiin prosesseihin, kuten sydän- ja aivoinfarkteihin, useisiin neoplasioihin ja ikääntymiseen.Tässä katsauksessa käsittelemme stressigeenien säätelyä, Hsp70-stressiproteiinienkliinisiä yhteyksiä ja niiden mahdollisia hoitosovelluksia iskeemisissä, neoplastisissaja degeneratiivisissa prosesseissa.
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