Proteoglycan metabolism and viability of articular cartilage explants as modulated by the frequency of intermittent loading

Sauerland, K.; Raiss, R.; Steinmeyer, Jürgen

doi:10.1016/s1063-4584(03)00007-4

Cited by 75 publications

(86 citation statements)

References 38 publications

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“…Generally, the lack of differences in GAG release in intact versus damage surfaces is contrary to multiple published hypotheses, according to which, collagen network damage causes increased fluid flow and fluid loss, leading to increased GAG loss and further matrix degradation before progressing to the ultimate development of OA. 7,20,41 It was expected that GAG release for damaged samples would be higher because the integrity of the superficial zone was compromised. Also, once the new articulating surface of the damaged samples became the middle zone, differences in composition, mechanical properties, collagen fiber orientation, and gene expression patterns of the superficial zone and middle zone 42 were expected to add to the increased wear.…”

Section: Discussionmentioning

confidence: 99%

“…6 To that end, effective in vitro models should provide controlled mechanical conditions to evaluate the temporal relationship between injury and response. 7 When developing studies to understand this relationship, models should account for the idea that 2 different insult types may lead to PTOA: (1) single, acute stress events and (2) chronic stress abnormalities accumulated over time from small mechanical insults. 5 For acute events, most cartilage injury models apply a single supraphysiologic impact to create the initial insult.…”

Section: Introductionmentioning

confidence: 99%

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Development of a Cartilage Shear-Damage Model to Investigate the Impact of Surface Injury on Chondrocytes and Extracellular Matrix Wear

et al. 2016

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Background. Many in vitro damage models investigate progression of cartilage degradation after a supraphysiologic, compressive impact at the surface and do not model shear-induced damage processes. Models also neglect the response to uninterrupted tribological stress after damage. It was hypothesized that shear-induced removal of the superficial zone would accelerate matrix degradation when damage was followed by continued load and articulation. Methods. Bovine cartilage underwent a 5-day test. Shear-damaged samples experienced 2 days of damage induction with articulation against polyethylene and then continued articulation against cartilage (CoC), articulation against metal (MoC), or rest as freeswelling control (FSC). Surface-intact samples were randomized to CoC, MoC, or FSC for the entire 5-day test. Samples were evaluated for chondrocyte viability, GAG (glycosaminoglycan) release (matrix wear surrogate), and histological integrity. Results. Shear induction wore away the superficial zone. Damaged samples began continued articulation with collagen matrix disruption and increased cell death compared to intact samples. In spite of the damaged surface, these samples did not exhibit higher GAG release than intact samples articulating against the same counterface (P = 0.782), contrary to our hypothesis. Differences in GAG release were found to be due to tribological testing against metal (P = 0.003). Conclusion. Shear-induced damage lowers chondrocyte viability and affects extracellular matrix integrity. Continued motion of either cartilage or metal against damaged surfaces did not increase wear compared with intact samples. We conjecture that favorable reorganization of the surface collagen fibers during articulation protected the underlying matrix. This finding suggests a potential window for clinical interventions to slow matrix degradation after traumatic incidents.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of a Cartilage Shear-Damage Model to Investigate the Impact of Surface Injury on Chondrocytes and Extracellular Matrix Wear

et al. 2016

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“…However, quantitative autoradiography showed that dynamic compression increased proteoglycan synthesis by chondrocytes located mainly near the explant periphery (10) in the region of maximal fluid flow, whereas the stimulatory effects of dynamic shear were observed throughout the explant (12), consistent with the more spatially uniform cyclic shear strain. Studies applying hydrostatic pressure to isolated bovine articular chondrocytes showed that moderate cyclic hydrostatic pressurization (0.5-5 megapascal, 0.1-1 Hz) increased biosynthesis (14,15), whereas high continuous hydrostatic pressure (Ͼ15 megapascal) decreases biosynthesis (14).…”

mentioning

confidence: 99%

Shear and Compression Differentially Regulate Clusters of Functionally Related Temporal Transcription Patterns in Cartilage Tissue

Fitzgerald

Jin

Grodzinsky

2006

Journal of Biological Chemistry

102

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Chondrocytes are subjected to a variety of biophysical forces and flows during physiological joint loading, including mechanical deformation, fluid flow, hydrostatic pressure, and streaming potentials; however, the role of these physical stimuli in regulating chondrocyte behavior is still being elucidated. To isolate the effects of these forces, we subjected intact cartilage explants to 1-24 h of continuous dynamic compression or dynamic shear loading at 0.1 Hz. We then measured the transcription levels of 25 genes known to be involved in cartilage homeostasis using real-time PCR and compared the gene expression profiles obtained from dynamic compression, dynamic shear, and our recent results on static compression amplitude and duration. Using clustering analysis, we determined that transcripts for proteins with similar function had correlated responses to loading. However, the temporal expression patterns were strongly dependent on the type of loading applied. Most matrix proteins were up-regulated by 24 h of dynamic compression or dynamic shear, but down-regulated by 24 h of 50% static compression, suggesting that cyclic matrix deformation is a key stimulator of matrix protein expression. Most matrix proteases were up-regulated by 24 h under all loading types. Transcription factors c-Fos and c-Jun maximally responded within 1 h to all loading types. Pre-incubating cartilage explants with either a chelator of intracellular calcium or an inhibitor of the cyclic AMP pathway demonstrated the involvement of both pathways in transcription induced by dynamic loading.Mechanical forces within synovial joints are known to influence the metabolic behavior of chondrocytes, the sole cell type of cartilage (1-3). Chondrocytes are responsible for the maintenance and turnover of the cartilage extracellular matrix, in particular the biosynthesis of type II collagen and proteoglycan (aggrecan), which in combination provide the tensile, shear, and compressive stiffness of cartilage. Cartilage thickness and proteoglycan content were found to be enhanced in load-bearing areas in vivo (4). Joint inactivity (1, 2) and injury (5) have been found to promote degradation of the extracellular matrix and to reduce cartilage load bearing capacity. The exact mechanisms by which mechanical forces influence the biological activity of chondrocytes are under intense study. In addition, the precise component(s) of the physical stimuli that induce such biological changes following joint movement are not known.The effects of mechanical loading on cartilage in vivo have been studied using intact human and animal cartilage explants in vitro to determine the precise biophysical forces and physicochemical changes that result (for reviews, see Refs. 6 and 7

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“…These studies invariably show an increase in matrix production during the withdrawal phase (Sah et al, 1989;Kim et al, 1994;Burton-Wurster et al, 1993;Neu et al, 2007). Finally, there remain a number of publications in which protein and proteoglycan synthesis is detected/regulated when measurements are made during cyclic or static loading (Palmoski and Brandt, 1984;Gray et al, 1988;Gray et al 1989;Sah et al, 1989;Larsson et al, 1991;Kim et al, 1994;Steinmeyer and Knue, 1997;Wong et al, 1999;Sauerland et al, 2003). In these cases, it is not possible to rationalise why our data are at odds.…”

Section: Lomas Et Al Translational Arrest In Loaded Cartilagementioning

confidence: 86%

“…The concept that cyclic mechanical stimulation of articular cartilage promotes synthesis of matrix proteins (Korver et al, 1992;van Kampen et al, 1994;Lee et al, 2003) and static stimulation leads to suppression of these molecules (Gray et al, 1988;Burton-Wurster et al, 1993) does not always hold true (Gray et al, 1989;Steinmeyer and Knue, 1997;Fehrenbacher et al, 2003;Ackermann and Steinmeyer, 2005). It is apparent, from close scrutiny of these papers, that control of anabolic cell processes C Lomas et al Translational arrest in loaded cartilage is dependent upon other complex variables such as the frequency of cyclic load (Larsson et al, 1991;Kim et al, 1994;Parkkinen et al, 1992;Parkkinen et al, 1993;Valhmu et al, 1998;Buschmann et al, 1999;Sauerland et al, 2003;Sah et al, 1989), the amplitude and duration of the load Bachrach et al, 1995), the nature of the force i.e. compressive versus shear (Fitzgerald et al, 2006;Neu et al, 2007) and, probably, the age and derivation of tissue in which the experiment is performed.…”

Section: Introductionmentioning

confidence: 99%

Cyclic mechanical load causes global translational arrest in articular chondrocytes: a process which is partially dependent upon PKR phosphorylation

Lomas¹,

Tang²,

Chanalaris³

et al. 2011

eCM

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The cellular mechanisms by which articular cartilage responds to load are poorly understood, but such responses may involve regulation at the level of protein translation rather than synthesis of mRNA. We investigated the role of translational control in cyclically (0.5 Hz, 0.1 Hz and 0.05 Hz) and statically loaded porcine articular cartilage explants. Messenger RNA was extracted for real time polymerase chain reaction (RT-PCR) and newly synthesised proteins were measured by their incorporation of radiolabelled 35 S[methionine/cysteine] or 35 SO 4 . Some medium from loaded and unloaded explants was immunoblotted for type II collagen, CTGF and TIMP3. The pathways that control protein translation were investigated by immunoblotting explant lysates for PKR, PERK (PKR like endoplasmic reticulum kinase), eIF2a (eukaryotic initiation factor 2a), eEFs (eukaryotic elongation factors), and AMP-dependent kinase. Explants were also loaded in the presence of inhibitors of PKR, the fi broblast growth factor (FGF) receptor and PI3 kinase. Cyclic loading caused complete global translational arrest as evidenced by a total suppression of new protein synthesis whilst maintaining mRNA levels. Translational arrest did not occur following static loading and was partly dependent upon the load frequency. There was a rebound increase in protein synthesis when labelling was performed after load had been withdrawn. Phosphorylation of PKR occurred in explants following cyclic load and inhibition of PKR modestly reversed suppression of newly synthesised proteins suggesting that PKR, at least in part, was responsible for loading induced translational arrest. These results show that translational control provides a rapid and potentially important mechanism for controlling the synthetic responses of articular chondrocytes in response to different types of mechanical load.

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Proteoglycan metabolism and viability of articular cartilage explants as modulated by the frequency of intermittent loading

Cited by 75 publications

References 38 publications

Development of a Cartilage Shear-Damage Model to Investigate the Impact of Surface Injury on Chondrocytes and Extracellular Matrix Wear

Development of a Cartilage Shear-Damage Model to Investigate the Impact of Surface Injury on Chondrocytes and Extracellular Matrix Wear

Shear and Compression Differentially Regulate Clusters of Functionally Related Temporal Transcription Patterns in Cartilage Tissue

Cyclic mechanical load causes global translational arrest in articular chondrocytes: a process which is partially dependent upon PKR phosphorylation

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