| 1. |
- Arokoski, Jari, et al.
(author)
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Nivelrikon etiopatogeneesi [Etiopathogenesis of osteoarthritis].
- 2001
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In: Duodecim. - : Duodecim. - 0012-7183 .- 2242-3281. ; 117:16, s. 1617-1626
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Journal article (peer-reviewed)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. |
- Haapala, Jussi, et al.
(author)
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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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In: Journal of Rheumatology. - : Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 23:9, s. 1586-1593
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Journal article (peer-reviewed)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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| 3. |
- Helminen, Heikki, et al.
(author)
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Kuormituksen vaikutus nivelrustoon [The effects of loading on articular cartilage].
- 1992
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In: Duodecim. - : Duodecim. - 0012-7183 .- 2242-3281. ; 108:12, s. 1097-1107
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Research review (peer-reviewed)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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| 4. |
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| 5. |
- Hyttinen, Mika, et al.
(author)
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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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In: Osteoarthritis and Cartilage. - : Saunders Elsevier. - 1063-4584 .- 1522-9653. ; 9:8, s. 694-701
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Journal article (peer-reviewed)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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| 6. |
- Jortikka, Matti, et al.
(author)
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A high sensitivity dot-blot assay for proteoglycans by cuprolinic blue precipitation.
- 1993
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In: Connective Tissue Research. - : Informa Healthcare. - 0300-8207 .- 1607-8438. ; 29:4, s. 263-272
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Journal article (peer-reviewed)abstract
- A highly sensitive blot-assay was developed for glycosaminoglycans (GAGs) and proteoglycans (PGs) utilizing a precipitation reaction by a cationic dye Cuprolinic Blue. The precipitates were deposited into 1-2 mm2 spots on nitrocellulose membrane by using a 96-well filtration apparatus. The dried sheet was digitized by a flat bed scanner and the intensity of the dots was quantitated by an image analysis software. The working range for chondroitin sulfate was 10-300 ng. The response of various GAGs differed according to the number of anionic groups, both sulphate and carboxyl groups being able to bind the dye. The sensitivity of the assay was decreased by high concentrations of GuC, CsC and protein, but not by nonionic detergents, common buffers and 8 M urea. Contact exposure to autoradiography film enabled quantitation of 25-250 DPM, and 1-10 DPM, of 35SO4-radioactivity in precipitated PGs after overnight and 14 days' exposures, respectively.
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| 7. |
- Jortikka, Matti, et al.
(author)
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Immobilisation causes longlasting matrix changes both in the immobilised and contralateral joint cartilage.
- 1997
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 56:4, s. 255-261
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The capacity of articular cartilage matrix to recover during 50 weeks of remobilisation after an atrophy caused by 11 weeks of immobilisation of the knee (stifle) joint in 90 degrees flexion starting at the age of 29 weeks, was studied in young beagle dogs.METHODS: Proteoglycan concentration (uronic acid) and synthesis ([35S]sulphate incorporation) were determined in six and three knee joint surface locations, respectively. Proteoglycans extracted from the cartilages were characterised by chemical determinations, gel filtration, and western blotting for chondroitin sulphate epitope 3B3.RESULTS: The proteoglycan concentrations that were reduced in all sample sites immediately after the immobilisation, remained 14-28% lower than controls after 50 weeks of remobilisation in the patella, the summit of medial femoral condyle, and the superior femoropatellar surface. In the contralateral joint, there was a 49% increase of proteoglycans in the inferior femoropatellar surface after remobilisation, while a 34% decrease was simultaneously noticed on the summit of the medial femoral condyle. Total proteoglycan synthesis was not significantly changed after immobilisation or 50 weeks' remobilisation in the treated or contralateral joint, compared with age matched controls. The chondroitin 6- to 4- sulphate ratio was reduced by immobilisation both in the radioactively labelled and the total tissue proteoglycans. In the remobilised joint, this ratio was restored in femur, while in tibia it remained at a level lower than controls. Neither immobilisation nor remobilisation induced epitopes recognised by the monoclonal antibody 3B3 on native (undigested) proteoglycans.CONCLUSION: These results show that the depletion of proteoglycans observed after 11 weeks of immobilisation was not completely restored in certain surface sites after 50 weeks of remobilisation. The significant changes that developed in the contralateral joint during the remobilisation period give further support to the idea that a permanent alteration of matrix metabolism results even from a temporary modification of loading pattern in immature joints.
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| 8. |
- Jortikka, Matti, et al.
(author)
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The role of microtubules in the regulation of proteoglycan synthesis in chondrocytes under hydrostatic pressure.
- 2000
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In: Archives of Biochemistry and Biophysics. - : Elsevier. - 0003-9861 .- 1096-0384. ; 374:2, s. 172-180
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Journal article (peer-reviewed)abstract
- Chondrocytes of the articular cartilage sense mechanical factors associated with joint loading, such as hydrostatic pressure, and maintain the homeostasis of the extracellular matrix by regulating the metabolism of proteoglycans (PGs) and collagens. Intermittent hydrostatic pressure stimulates, while continuous high hydrostatic pressure inhibits, the biosynthesis of PGs. High continuous hydrostatic pressure also changes the structure of cytoskeleton and Golgi complex in cultured chondrocytes. Using microtubule (MT)-affecting drugs nocodazole and taxol as tools we examined whether MTs are involved in the regulation of PG synthesis in pressurized primary chondrocyte monolayer cultures. Disruption of the microtubular array by nocodazole inhibited [(35)S]sulfate incorporation by 39-48%, while MT stabilization by taxol caused maximally a 17% inhibition. Continuous hydrostatic pressure further decreased the synthesis by 34-42% in nocodazole-treated cultures. This suggests that high pressure exerts its inhibitory effect through mechanisms independent of MTs. On the other hand, nocodazole and taxol both prevented the stimulation of PG synthesis by cyclic 0. 5 Hz, 5 MPa hydrostatic pressure. The drugs did not affect the structural and functional properties of the PGs, and none of the treatments significantly affected cell viability, as indicated by the high level of PG synthesis 24-48 h after the release of drugs and/or high hydrostatic pressure. Our data on two-dimensional chondrocyte cultures indicate that inhibition of PG synthesis by continuous high hydrostatic pressure does not interfere with the MT-dependent vesicle traffic, while the stimulation of synthesis by cyclic pressure does not occur if the dynamic nature of MTs is disturbed by nocodazole. Similar phenomena may operate in cartilage matrix embedded chondrocytes.
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| 9. |
- Kiviranta, Ilkka, et al.
(author)
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Effects of mechanical loading and immobilization on the articular cartilage
- 1997
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In: Bailliere's Clinical Orthopaedics. - 1074-8814. ; 2:1, s. 109-122
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Research review (peer-reviewed)abstract
- Articular cartilage provides nearly frictionless surfaces for joint movemants and reduces contact pressures, protecting the underlying suchondral bone from excess stress. The unique properties of articular cartilage are based on the interaction of the main components of the extracellular matrix: proteoglycans (PGs), collagen and interstitial fluid. Animal experiments and in vitro studies demonstrate that one of the most important regulators of the extracellular matrix metabolism is mechanical loading acting on the joints. Unloading and immobilization leads to PG depletion and softening of articular cartilage, increasing the risk of permanent cartilage degeneration. Moderate running exercise and increased weight bearing increases cartilage thickness, PG concentration and improves biomechanical properties of articular cartilage. With further increase in training intensity this positive influence of exercise disappears and cartilage shows changes analogous to immobilization of the joint, i.e. PG depletion and softening of the tissue. In humans most epidemiological studies have failed to prove the connection between running training and cartilage degeneration, but there is evidence that sports activities exposing joints to impact loading might increase the risk of osteoarthrosis.
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| 10. |
- Lammi, Mikko, 1961-, et al.
(author)
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Adaptation of canine femoral head articular cartilage to long distance running exercise in young beagles.
- 1993
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In: Annals of the Rheumatic Diseases. - : British Medical Journal. - 0003-4967 .- 1468-2060. ; 52:5, s. 369-377
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To study the effects of long term (one year), long distance (up to 40 km/day) running on the metabolism of articular cartilage the biosynthesis of proteoglycans was examined by in vitro labelling of anterior (weight bearing) and posterior (less weight bearing) areas of the femoral head from young beagles.METHODS: Total sulphate incorporation rates were determined and distribution of the incorporated sulphate was localised by quantitative autoradiography. Concentration and extractability of the proteoglycans were determined, and proteoglycan structures were investigated by gel filtration chromatography, agarose gel electrophoresis, and chemical determinations.RESULTS: In the less weight bearing area the amount of extractable proteoglycans was decreased (p < or = 0.02), simultaneously with an increased concentration of residual glycosaminoglycans in the tissue after 4 M GuCl extraction (p < or = 0.05). In control animals proteoglycan synthesis was most active in the deep zone of the cartilage, whereas exercise increased synthesis in the intermediate zone. There was a tendency to a lower keratan: chondroitin sulphate ratio in the running dogs. No macroscopical or microscopical signs of articular degeneration or injury were visible in any of the animals.CONCLUSION: The articular cartilage of the femoral head showed a great capacity to adapt to the increased mechanical loading. The reduced proteoglycan extractability in the less weight bearing area changed it similar to the weight bearing area, suggesting that the low extractability of proteoglycans reflects the long term loading history of articular cartilage. The congruency of the femoral head with acetabulum seems to protect the cartilage from the untoward alterations that occur in the femoral condyles subjected to a similar running programme.
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