Solujen käyttäytyminen kuormitettaessa nivelrikkoista rustoa: kokeellinen ja teoreettinen tarkastelu [Biomechanical Behaviour of Chondrocytes in Mechanically Loaded Osteoarthritic (OA) Cartilage: Experimental and Theoretical Analysis]

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URL: https://erepo.uef.fi/handle/123456789/10894

Abstract (Finnish)

Rustosolut vastaavat ruston aineenvaihdunnasta ja soluväliaineen muodostuksesta. Rustosolujen toiminta nivelrikon synnyn ja etenemisen aikana tulisi tuntea paremmin sairauden syntymekanismien selvittämiseksi. Solujen tilavuuden on havaittu kasvavan katkaistun eturistisiteen nivelrikkomallissa, kun rustoa on kuormitettu mekaanisesti.

Työn tarkoituksena oli selvittää onko solutilavuuden kasvu selitettävissä nivelrikossa tapahtuvien rustokudoksen ominaisuuksien muutosten avulla. Turpoavan säievahvisteisen mallin (FRPES) avulla tutkittiin rustosolua ympäröivän solun lähiympäristön (PCM) mekaanisten ominaisuuksien vaikutusta rustosolun tilavuuteen. Malliin implementoitiin kokeellisen aineiston mukaiset terveen ja nivelrikkoisen ruston soluväliaineen, solun lähiympäristön ja solun ominaisuudet. Kokeellisten mittausten perusteella nivelrikkomallin ruston soluväliaineen sidottua varaustiheyttä (FCD) ja kollageenijäykkyyttä laskettiin sekä nestepitoisuutta nostettiin. Mallien solutilavuuksia verrattiin kokeellisesti havaittuihin solutilavuuksiin, missä nivelrikon oli annettu kehittyä 4 ja 9 viikkoa.

Työssä havaittiin solun lähiympäristön sidotun varaustiheyden ja kollageenijäykkyyden pienenemisen kasvattavan solutilavuutta nivelrikkoa kuvaavassa mallissa. Tervettä rustoa kuvaavan mallin solutilavuus pieneni, mikä on konsistenssissa aiempien tutkimusten kanssa. Mallisimulaatiot olivat yhteneviä kokeellisesti havaittujen solutilavuuksien kanssa. Tulokset osoittavat, että kokeellisesti havaittu nivelrikossa tapahtuva solutilavuuden kasvu voidaan ainakin osittain selittää solun lähiympäristön ominaisuuksien muutoksilla. Kasvaneen solutilavuuden on todettu heikentävän rustosolun synteesiä, mikä voi aiheuttaa nivelrikon synnyn tai edesauttaa sen kehittymistä.

Abstract (English)

Cartilage cells i.e. chonrocytes are responsible for cartilage metabolism and control synthesis and assembly of an extracellular matrix (ECM). In order to investigate the mechanisms behind early osteoarthritis (OA) the function of chonrocytes should be known better during the development and progression of the OA. Earlier studies have observed a cell volume increase in mechanically loaded cartilage, obtained from an anterior cruciate ligament transected (ACLT) cartilage.

The aim of this study was to investigate, can the cell volume behaviour be explained with the experimentally detected changes in the ECM and pericellular matrix (PCM). Based on our experimental tests the compositional, structural and mechanical parameters of the ECM, PCM and cell for healthy and OA cartilage were obtained and implemented into the fibril-reinforced poroelastic model with swelling properties. Consistent with the experimental tests, fixed charge density (FCD) and collagen modulus were decreased and a fluid fraction was increased in OA model. Finite element simulations were compared with the experimentally detected cell volume changes in mechanically loaded rabbit cartilage, obtained from the anterior cruciate ligament transected (ACLT) rabbit knees harvested four and nine weeks after the operation.

We found that decrease in pericellular FCD and collagen modulus increased the cell volume in the OA model. Consistent with earlier studies cell volume decreased in healthy cartilage. Findings suggest that increase in cell volume in OA cartilage is, at least partially, explained by the integrity of the PCM. Earlier studies have been shown, that increase in cell volume has been shown to decrease cell synthesis and metabolism. Changes in the PCM composition, present in OA, may lead increased cell volume, thus decreasing cell synthesis and increasing the possibility in development or progression of the OA.

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