TY - JOUR
T1 - Compression-induced changes in the shape and volume of the chondrocyte nucleus
AU - Guilak, Farshid
N1 - Funding Information:
Chondrocyte volume is an important regulator of 1993).A lterations in cell and nnclear volume,p resumably metabolic activity (Urban et al., 1993).T he mechanisms through changesin extracellular osmolar~ty~m ay there-responsiblefo r the observed decreasein volume of the fore have an indirect regulatory influenceo n cell activity chondrocytesa nd the nuclei in responseto compression through changesin the intranuclear ionic ~nviro~rn~~t are not clear,b ut are most likely regulatedb y changesin (Vanden Broeck et al., 1992).A lternatively, mechanicaI the apparent composition and physicochemicapl roper-signalsm ay have a direct effect on intranuclear transcrip-ties of the pericellular region. The extracellular matrix of tion or translation processesF. or example, it bas been articular cartilage is composed primarily of water proposed that mechanical perturbations of nuclear (75-80% by weight) with a population of dissolveda n-matrix proteins may affect gene expressionb y altering ions and cations (e.g.f -H+,N a+, Ca”, Cl-). The remain-DNA conformation or by exposingo r ob$~uringm oiecin-ing solid fraction of matrix consistsp redominantly of lar binding sites during mRNA transcription (Ingber, a network of collagenf ibersw ithin which large,n egative-1993). ly charged proteoglycan aggregates are entangled The role of cell and nuclear deformation in regulating ~~a~o~da§, 1979). Compressived ilatation of the ex-cell metabolismi s still not clear. Significantc ircumstan-tracellular -matrix resultsi n exudation of the interstitial tial evidencee xists to implicate a physical connection fluid and an increasein the tissuef ixed-charge density, betweent he cytoskeletona nd the extracellu!ar matrix in increasing the Donnan osmotic pressure outside the the processo f mechanicals ignal transduction (Fienta chondrocytes( Lai et al., 1991;M aroudas, 1979).A s the and Coffey, 1992;I ngber, 1991;W ang et al., 1993).T he cell membranei s highly permeablet o water, an increase overall processo f cartilage adaptation and remodelingin of the extracellular osmolarity would be expected to responseto mechanicallo ading most likely involves in-causea decreasein chondrocyte volume (Gu et al., 1994; teractionsb etweenm ultiple signalingp athways.a nd it is Urban et ui., 19931c, onsistentw ith the presentf indings. important to note that there is substantiali nformation Alternatively, or in combination with osmotic effects, pointing to the involvement of the traditional second volume changesm ay be due to mechanically induced messengercsa scadesa s (Bourret and Rodan: 1976; exudation of intracellular water and solutes.H owever, Guilak et al., 1994a;S tockwell, 1987).Q ~ar~ti~6atioõ~f the finding that cytochalasin treatment did not have the relationshipb etweent he mechanicael nvironmento f a significant effect on the nuclear volume decreasew ith the extracellularm atrix and the b~omechanicãñ d bio-compressionis consistentw ith the hypothesis that nu-logical behavior of the chondroeytesi s a first step in clear volume changesr esultfrom osmoticp ressureg radi-understandingt he role that these phenomenap lay in ents in the extracellular matrix and cytoplasm, rather regulating cell activity and phenotypic expression, than from purely mechanicale ffects.Cell and nuclear volume changesm ay alsoo ccur through an active regula- tory processw hich is stimulatedb y mechanicapl erturba- tion Previous studiesh ave observedt hat chondrocytes compressewd ithin an agaroseg el exhibit greaterc hanges in cross-sectional area than would be predicted by a purely mechanicalo r osmotic responses, uggestinga n ponent of volume regulation (Freemane t al., 1994).T he overall responseo f the cell to swelling or shrinkagem ost likely involves the actin cytoskeleton as well (Mills et al,, 1994). The findings of the presents tudy confirm that mechan- ical deformations are transmitted acrosst he cell mem- brane and therefore could serve,i n effect, asi ntracellular ‘second messengersin’ transducing matrix loads. Al- though the specific mechanismso f signaling are not known, several potential pathways exist through which nuclear deformation may regulatec ell activity. Changes in nuclear shapeo r volume may alter the properties of the pare complexo f the nuclear membranew, hich regu- lates the transport of nucleic acids, proteins, and ions betweent he cytoplasma nd nucleus( Gerace,1 992).F eld- herr and Akin (1993)d emonstratedth at the rate of trans- port of nu$leo~lasm~~-moagteodld particles into the nu- cleus,a s well as tbe functional size of the nuclear pores, was greater in cells which had a more flattened shape. There is also evidencet hat the nuclear envelope,s imilar to the cell membrane,c ontainsi on channelsw hich regu- fate transport between the nucleus and cytoplasm in responseto osmotic changes( Innocenti and Mazzanti, Acknowledgements-This study was supported by a grant From the Whitaker Foundation and by the Virginia Flowers Baker Endowment. The author would like to thank Dr Henry 3. Donahue for many insightful discussions and Dr Tobias Meyer for use of his confocal microscope.
PY - 1995/12
Y1 - 1995/12
N2 - Changes in cell shape and volume are believed to play a role in the process of mechanical signal transduction by chondrocytes in articular cartilage. One proposed pathway through which chondrocyte deformation may be transduced to an intracellular signal is through cytoskeletally mediated deformation of intracellular organelles, and more specifically, of the cell nucleus. In this study, confocal scanning laser microscopy was used to perform in situ three-dimensional morphometric analyses of the nuclei of viable condrocytes during controlled compression of articular cartilage explants from the canine patellofemoral groove. Unconfined compression of the tissue to a 15% surface-to-surface strain resulted in a significant decrease of chondrocyte height and volume by 14.7 ± 6.4 and 11.4 ± 8.4%, respectively, and of nuclear height and volume by 8.8 ± 6.2% and 9.8 ± 8.8%, respectively. Disruption of the actin cytoskeleton using cytochalasin D altered the relationship between matrix deformation and changes in nuclear height and shape, but not volume. The morphology and deformation behavior of the chondrocytes were not affected by cytochalasin treatment. These results suggest that the actin cytoskeleton plays an important role in the link between compression of the extracellular matrix and deformation of the chondrocyte nuclei and imply that chondrocytes and their nuclei undergo significant changes in shape and volume in vivo.
AB - Changes in cell shape and volume are believed to play a role in the process of mechanical signal transduction by chondrocytes in articular cartilage. One proposed pathway through which chondrocyte deformation may be transduced to an intracellular signal is through cytoskeletally mediated deformation of intracellular organelles, and more specifically, of the cell nucleus. In this study, confocal scanning laser microscopy was used to perform in situ three-dimensional morphometric analyses of the nuclei of viable condrocytes during controlled compression of articular cartilage explants from the canine patellofemoral groove. Unconfined compression of the tissue to a 15% surface-to-surface strain resulted in a significant decrease of chondrocyte height and volume by 14.7 ± 6.4 and 11.4 ± 8.4%, respectively, and of nuclear height and volume by 8.8 ± 6.2% and 9.8 ± 8.8%, respectively. Disruption of the actin cytoskeleton using cytochalasin D altered the relationship between matrix deformation and changes in nuclear height and shape, but not volume. The morphology and deformation behavior of the chondrocytes were not affected by cytochalasin treatment. These results suggest that the actin cytoskeleton plays an important role in the link between compression of the extracellular matrix and deformation of the chondrocyte nuclei and imply that chondrocytes and their nuclei undergo significant changes in shape and volume in vivo.
KW - Actin micro-filament
KW - Articular cartilage
KW - Confocal microscopy
KW - Cytochalasin D
KW - Cytoskeleton
KW - Mechanical signal transduction
UR - http://www.scopus.com/inward/record.url?scp=0029584101&partnerID=8YFLogxK
U2 - 10.1016/0021-9290(95)00100-X
DO - 10.1016/0021-9290(95)00100-X
M3 - Article
C2 - 8666592
AN - SCOPUS:0029584101
SN - 0021-9290
VL - 28
SP - 1529
EP - 1541
JO - Journal of Biomechanics
JF - Journal of Biomechanics
IS - 12
ER -