Altered Golgi apparatus in hydrostatically loaded articular cartilage chondrocytes.

Parkkinen, Jyrki; Lammi, Mikko J.; Pelttari, Alpo; Helminen, Heikki J.; Tammi, Markku; Virtanen, Ismo

doi:10.1136/ard.52.3.192

Cited by 66 publications

(31 citation statements)

References 24 publications

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“…Our results agree with those of previous studies (34,35,46), demonstrating that chondrocytes, like other cells, respond to mechanical loads in monolayer culture. In monolayer culture, calvarial bone cells release prostaglandin E2 in response to cyclic biaxial mechanical strains (4) and neonatal rat cardiac myocytes increase c-fos gene expression, total RNA levels, and phosphoinositide turnover (23) in response to stretching.…”

Section: Discussionsupporting

confidence: 96%

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In vitro stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure

Smith

Rusk

Ellison

et al. 1996

Journal Orthopaedic Research

242

133

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This study tested the effects of hydrostatic pressure (10 MPa) on adult articular chondrocyte mRNA and extracellular matrix synthesis in vitro. High density primary cultures of bovine chondrocytes were exposed to hydrostatic pressure applied intermittently at 1 Hz or constantly for 4 hours in serum-free medium or in medium containing 1% fetal bovine serum. mRNAs for aggrecan, types I and II collagen, and beta-actin were analyzed by Northern blots and quantified by slot blots. Proteoglycan synthesis was quantified by 35SO4 uptake into cetylpyridinium chloride-precipitable glycosaminoglycans, and cell-associated aggrecan and type-II collagen were detected by immunohistochemical techniques. In serum-free medium, intermittent pressure increased aggrecan mRNA signal by 14% and constant pressure decreased type-II collagen mRNA signal by 16% (p < 0.05). In the presence of 1% fetal bovine serum, intermittent pressure increased aggrecan and type-II collagen mRNA signals by 31% (p < 0.01) and 36% (p < 0.001), respectively, whereas constant pressure had no effect on either mRNA. Intermittent and constant pressure stimulated glycosaminoglycan synthesis 65% (p < 0.001) and 32% (p < 0.05), respectively. Immunohistochemical detection of cell-associated aggrecan and type-II collagen was increased in response to both intermittent and constant pressure. These data support the hypothesis that physiologic hydrostatic pressure directly influences the extracellular matrix metabolism of articular chondrocytes.

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Section: Discussionsupporting

confidence: 96%

“…At 30 MPa, continuous but not cyclic hydrostatic pressure alters chondrocyte Golgi apparatus and decreases proteoglycan synthesis (35).…”

Section: Figmentioning

confidence: 99%

In vitro stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure

Smith

Rusk

Ellison

et al. 1996

Journal Orthopaedic Research

242

133

View full text Add to dashboard Cite

show abstract

“…Earlier reports of the effects of HP have shown that continuous high HP leads to a reversible depolymerization of microtubules in vitro (50), a change from the normal stacked appearance of the Golgi apparatus to a tightly packed perinuclear clump (33), and an inhibition of total proteoglycan and protein synthesis in bovine chondrocytes (32,34). In line with our results, a 50-MPa HP treatment was recently shown to increase hsp70 mRNA levels in chondrocyte-like HCS-2͞8 cells (51).…”

Section: Discussionsupporting

confidence: 81%

“…High continuous hydrostatic pressure (HP) inhibits proteoglycan synthesis and secretion, reduces the steady-state level of aggrecan mRNA, alters the shape of the Golgi apparatus, and inhibits the stress fiber organization of microfilaments (32)(33)(34)(35). These findings prompted us to investigate whether such conditions would be adverse and induce stress response in the cells that synthesize cartilage-specific macromolecules.…”

mentioning

confidence: 99%

Hsp70 accumulation in chondrocytic cells exposed to high continuous hydrostatic pressure coincides with mRNA stabilization rather than transcriptional activation

Kaarniranta

Elo

Sironen

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

140

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In response to various stress stimuli, heat shock genes are induced to express heat shock proteins (Hsps). Previous studies have revealed that expression of heat shock genes is regulated both at transcriptional and posttranscriptional level, and the rapid transcriptional induction of heat shock genes involves activation of the specific transcription factor, heat shock factor 1 (HSF1). Furthermore, the transcriptional induction can vary in intensity and kinetics in a signal-and cell-type-dependent manner. In this study, we demonstrate that mechanical loading in the form of hydrostatic pressure increases heat shock gene expression in human chondrocyte-like cells. The response to continuous high hydrostatic pressure was characterized by elevated mRNA and protein levels of Hsp70, without activation of HSF1 and transcriptional induction of hsp70 gene. The increased expression of Hsp70 was mediated through stabilization of hsp70 mRNA molecules. Interestingly, in contrast to static pressurization, cyclic hydrostatic loading did not result in the induction of heat shock genes. Our findings show that hsp70 gene expression is regulated posttranscriptionally without transcriptional induction in chondrocyte-like cells upon exposure to high continuous hydrostatic pressure. We suggest that the posttranscriptional regulation in the form of hsp70 mRNA stabilization provides an additional mode of heat shock gene regulation that is likely to be of significant importance in certain forms of stress.

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“…In addition, loading may affect the apparatus for transcription and translation differently. Studies (37) have shown that high pressure can cause changes in cell morphology and disorganization of the Golgi and microtubules in chondrocytes. Compression of cartilage explants also reduces cell volume and the volumes of several intracellular organelles; however, the volume of the Golgi remains unaffected by static compression of up to 50% strain (38).…”

Section: Discussionmentioning

confidence: 99%

Mechanical Compression of Cartilage Explants Induces Multiple Time-dependent Gene Expression Patterns and Involves Intracellular Calcium and Cyclic AMP

Fitzgerald

Jin

Dean

et al. 2004

Journal of Biological Chemistry

224

184

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Chondrocytes are influenced by mechanical forces to remodel cartilage extracellular matrix. Previous studies have demonstrated the effects of mechanical forces on changes in biosynthesis and mRNA levels of particular extracellular matrix molecules, and have identified certain signaling pathways that may be involved. However, the broad extent and kinetics of mechano-regulation of gene transcription has not been studied in depth. We applied static compressive strains to bovine cartilage explants for periods between 1 and 24 h and measured the response of 28 genes using real time PCR. Compression time courses were also performed in the presence of an intracellular calcium chelator or an inhibitor of cyclic AMP-activated protein kinase A. Cluster analysis of the data revealed four main expression patterns: two groups containing either transiently up-regulated or duration-enhanced expression profiles could each be subdivided into genes that did or did not require intracellular calcium release and cyclic AMP-activated protein kinase A for their mechano-regulation. Transcription levels for aggrecan, type II collagen, and link protein were up-regulated ϳ2-3-fold during the first 8 h of 50% compression and subsequently down-regulated to levels below that of free-swelling controls by 24 h. Transcription levels of matrix metalloproteinases-3, -9, and -13, aggrecanase-1, and the matrix protease regulator cyclooxygenase-2 increased with the duration of 50% compression 2-16-fold by 24 h. Thus, transcription of proteins involved in matrix remodeling and catabolism dominated over anabolic matrix proteins as the duration of static compression increased. Immediate early genes c-fos and c-jun were dramatically up-regulated 6 -30-fold, respectively, during the first 8 h of 50% compression and remained up-regulated after 24 h. Articular cartilage is responsible for the smooth articulation of synovial joints during locomotion. Chondrocytes within cartilage constantly remodel the extracellular matrix (ECM) 1 of the tissue throughout life. The major load-bearing constituents of the ECM are type II collagen and aggregates of the proteoglycan, aggrecan, which provide the tensile and compressive stiffness of the tissue, respectively. Also present in the ECM are families of matrix proteinases, tissue inhibitors of matrix metalloproteinases (TIMPs), growth factors, and cytokines that together regulate ECM remodeling and turnover in health and disease (1). It is known that mechanical exercise of the knee joint in vivo increases the density of aggrecan in cartilage (2), whereas knee joint inactivity results in decreased aggrecan deposition (3, 4). Traumatic injury to cartilage diminishes mechanical strength and leads to excessive catabolism of the ECM, increasing the risk of osteoarthritis later in life (5).A number of model systems have been developed to simulate various aspects of the mechanical loading forces experienced by articular cartilage in vivo. Compressive and shear forces have been applied to cartilage explants and chondrocyte cul...

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Altered Golgi apparatus in hydrostatically loaded articular cartilage chondrocytes.

Abstract: Objectives Articular cartilage proteo-

Cited by 66 publications

References 24 publications

In vitro stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure

In vitro stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure

Hsp70 accumulation in chondrocytic cells exposed to high continuous hydrostatic pressure coincides with mRNA stabilization rather than transcriptional activation

Mechanical Compression of Cartilage Explants Induces Multiple Time-dependent Gene Expression Patterns and Involves Intracellular Calcium and Cyclic AMP

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