| 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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High hydrostatic pressure inhibits the biosynthesis of eukaryotic elongation factor-2.
- 2005
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Ingår i: Journal of Cellular Biochemistry. - : John Wiley & Sons. - 0730-2312 .- 1097-4644. ; 94:3, s. 497-507
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Tidskriftsartikel (refereegranskat)abstract
- High continuous hydrostatic pressure is known to inhibit the total cellular protein synthesis. In this study, our goal was to identify pressure-regulated proteins by using two dimensional gel electrophoresis and mass spectrometry. This analysis showed that under 30 MPa continuous hydrostatic pressure the biosynthesis of eukaryotic elongation factor-2 (eEF-2) was inhibited both in HeLa carcinoma and T/C28a4 chondrocytic cell lines. Western blot analysis of HeLa cells revealed that the cellular protein level of eEF-2 decreased by 40%-50% within 12 h of the pressure treatment. However, the steady-state mRNA level of eEF-2 was not affected by the pressure. Cycloheximide addition after 4 h-pressure treatment suggested that the half-life of eEF-2 protein was shorter in pressurized cells. eEF-2 is responsible for the translocation of ribosome along the specific mRNA during translation, and its phosphorylation prevents the ribosomal translocation. Therefore, increased phosphorylation of eEF-2 was considered as one mechanism that could explain the reduced level of protein synthesis in pressurized HeLa cell cultures. However, Western blot analysis with an antibody recognizing the Thr56-phosphorylated form of eEF-2 showed that phosphorylation of eEF-2 was not elevated in pressurized samples. In conclusion, the inhibition of protein synthesis under high pressure occurs independent of the phosphorylation of eEF-2. However, this inhibition may result from the decrease of cellular eEF-2 protein.
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| 4. |
- Elo, Mika, et al.
(författare)
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Hsp90 inhibitor geldanamycin increases hsp70 mRNA stabilisation but fails to activate HSF1 in cells exposed to hydrostatic pressure.
- 2005
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier. - 0006-3002 .- 1878-2434. ; 1743:1-2, s. 115-119
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Tidskriftsartikel (refereegranskat)abstract
- High hydrostatic pressure (HP) increases Hsp70 protein and mRNA levels by increasing the mRNA half-life without activation of HSF1 transcription factor. We investigated whether this change in gene expression requires Hsp90, previously shown to regulate hsp70 genes via HSF1. In HeLa cells, both HP and Hsp90 inhibitor geldanamycin (GA) up-regulated Hsp70 expression through mRNA stabilisation. GA, unlike HP, increased HSF1 activation. However, when exposures were used together a marked Hsp70 response was observed with mRNA stabilisation without coincidence of HSF1 activation. Our data suggests that Hsp90 is involved in hsp70 mRNA stabilisation and the HSF1 activation can be suppressed by high HP.
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| 5. |
- 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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| 6. |
- 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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| 7. |
- Haapala, Jussi, et al.
(författare)
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Coordinated regulation of hyaluronan and aggrecan content in the articular cartilage of immobilized and exercised dogs.
- 1996
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Ingår i: Journal of Rheumatology. - : Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 23:9, s. 1586-1593
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the influence of joint loading and immobilization on articular cartilage hyaluronan concentration and histological distribution in the knee joints of young dogs subjected to 11 weeks' immobilization by splinting, and 15 weeks' running exercise at a rate of 40 km/day.METHODS: The amount of hyaluronan in articular cartilage was determined by a competitive binding assay using a biotinylated hyaluronan binding complex (HABC) of aggrecan and link protein. Histologic sections were stained for the localization of hyaluronan with the HABC probe. Extracted proteoglycans were characterized by sodium dodecyl sulfate agarose gel electrophoresis.RESULTS: Immobilization significantly reduced the concentration of hyaluronan in all sites studied (tibial and femoral condyles, patellar surface of femur). The proportion of hyaluronan to total uronic acid (mainly from aggrecan) remained unchanged because of a concurrent decrease in aggrecan. The ratio of hyaluronan and aggrecan remained constant also in runners. The staining pattern of free hyaluronan in the tissue sections and the electrophoretic mobility of the extracted proteoglycans were not affected by the different loading regimes.CONCLUSION: Reduced joint loading due to splint immobilization significantly decreases both hyaluronan and aggrecan in the articular cartilage. The remarkably parallel changes in aggrecan and hyaluronan content suggest that joint loading exerts a coordinated influence on their metabolism.
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| 8. |
- Haapala, Jussi, et al.
(författare)
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Remobilization does not fully restore immobilization induced articular cartilage atrophy.
- 1999
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Ingår i: Clinical Orthopaedics and Related Research. - : Lippincott Williams & Wilkins. - 0009-921X .- 1528-1132. ; :362, s. 218-229
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Tidskriftsartikel (refereegranskat)abstract
- The recovery of articular cartilage from immobilization induced atrophy was studied. The right hind limbs of 29-week-old beagle dogs were immobilized for 11 weeks and then remobilized for 50 weeks. Cartilage from the immobilized knee was compared with tissue from age matched control animals. After the immobilization period, uncalcified articular cartilage glycosaminoglycan concentration was reduced by 20% to 23%, the reduction being largest (44%) in the superficial zone. The collagen fibril network showed no significant changes, but the amount of collagen crosslinks was reduced (13.5%) during immobilization. After remobilization, glycosaminoglycan concentration was restored at most sites, except for in the upper parts of uncalcified cartilage in the medial femoral and tibial condyles (9% to 17% less glycosaminoglycans than in controls). The incorporation of 35SO4 was not changed, and remobilization also did not alter the birefringence of collagen fibrils. Remobilization restored the proportion of collagen crosslinks to the control level. The changes induced by joint unloading were reversible at most sites investigated, but full restoration of articular cartilage glycosaminoglycan concentration was not obtained in all sites, even after remobilization for 50 weeks. This suggests that lengthy immobilization of a joint can cause long lasting articular cartilage proteoglycan alterations at the same time as collagen organization remains largely unchanged. Because proteoglycans exert strong influence on the biomechanical properties of cartilage, lengthy immobilization may jeopardize the well being of articular cartilage.
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| 9. |
- Helminen, Heikki, et al.
(författare)
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Kuormituksen vaikutus nivelrustoon [The effects of loading on articular cartilage].
- 1992
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Ingår i: Duodecim. - : Duodecim. - 0012-7183 .- 2242-3281. ; 108:12, s. 1097-1107
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Forskningsöversikt (refereegranskat)abstract
- Nivelen kuormitus on tärkeimpiä nivelruston aineenvaihduntaan ja rakenteeseen vaikuttavia fysiologisia tekijöitä. Kohtuullinen rytminen kuormitus lisää nuoren ihmisen nivelruston proteoglykaanipitoisuutta. Tämän vaikutuksesta rusto jäykistyy ja kasvaa paksuutta. Hyvin voimakas kuormitus ei aiheuta tällaista positiivista vastetta. Toisaalta nivelkuormituksen puuttuminen pienentää ruston proteoglykaanipitoisuutta ja heikentää kimmo-ominaisuuksia. Nämä surkastumismuutokset ovat suurimmaksi osaksi–elleivät kokonaan–korjautuvia. Kohtuullisella nivelkuormituksella voidaan siis ylläpitää ja parantaa nivelruston ominaisuuksia. Pitkäaikaisen liikkumattomuuden jälkeen nivelrusto on heikompi kuin normaalisti ja voi vaurioitua niveltä voimakkaasti kuormitettaessa. Siksi nivelen kuormitusta pitää lisätä toipumisvaiheessa vähitellen.
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| 10. |
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