In Vitro Models for Investigation of the Effects of Acute Mechanical Injury on Cartilage

Patwari, Parth; Fay, Jakob; Cook, Michael N.; Badger, Alison M.; Kerin, Alex; Lark, Michael W.; Grodzinsky, Alan J.

doi:10.1097/00003086-200110001-00007

Cited by 45 publications

(39 citation statements)

References 37 publications

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“…Since injurious mechanical stress has been recognized as one of the causes of OA development, cartilage overloading has been the focus of a number of studies aimed at mimicking unfavorable mechanical conditions that cartilage could experience (Fitzgerald et al, 2006a;Kurz et al, 2005;Lin et al, 2004;Patwari et al, 2001;Torzilli et al, 2010). Although these studies provided insight into the biological response of cartilage to static and cyclic loading of different duration, normal force magnitude and frequency, their uni-axial design presents some limitations.…”

Section: Introductionmentioning

confidence: 99%

Coupling plowing of cartilage explants with gene expression in models for synovial joints

Correro-Shahgaldian

Colombo

Spencer

et al. 2011

Journal of Biomechanics

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Articular cartilage undergoes complex loading modalities generally including sliding, rolling and plowing (i.e. the compression by a condyle normally to the tissue surface under simultaneously tangential displacement, thus generating a tractional force due to tissue deformation). Although in in vivo studies it was shown that excessive plowing can lead to osteoarthritis, little quantitative experimental work on this loading modality and its mechanobiological effects is available in the literature. Therefore, a rolling/plowing explant test system has been developed to study the effect on pristine cartilage of plowing at different perpendicular forces. Cartilage strips harvested from bovine nasal septa of 12-months-old calves were subjected for 2h to a plowing-regime with indenter normal force of 50 or 100 N and a sliding speed of 10 mm s(-1). 50 N produced a tractional force of 1.2±0.3N, whereas 100 N generated a tractional force of 8.0±1.4N. Furthermore, quantitative-real-time polymerase chain reaction experiments showed that TIMP-1 was 2.5x up-regulated after 50 N plowing and 2x after 100 N plowing, indicating an ongoing remodeling process. The expression of collagen type-I was not affected after 50 N plowing but it was up-regulated (6.6x) after 100 N plowing, suggesting a possible progression to an injury stage of the cartilage, as previously reported in cartilage of osteoarthritic patients. We conclude that plowing as performed by our mimetic system at the chosen experimental parameters induces changes in gene expression depending on the tractional force, which, in turn, relates to the applied normal force. . 50 N produced a tractional force of 1.2 ± 0.3 N, whereas 100 N generated a tractional force of 8.0 ± 1.4 N. Furthermore, quantitativereal-time polymerase chain reaction experiments showed that TIMP-1 was 2.5x upregulated after 50 N plowing and 2x after 100 N plowing, indicating an ongoing remodeling process. The expression of Collagen type I was not affected after 50 N plowing but it was up-regulated (6.6x) after 100 N plowing, suggesting a possible progression to an injury stage of the cartilage, as previously reported in cartilage of osteoarthritic patients. We conclude that plowing as performed by our mimetic system at the chosen experimental parameters induces changes in gene expression depending on the tractional force, which, in turn, relates to the applied normal force.

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Section: Introductionmentioning

confidence: 99%

Coupling plowing of cartilage explants with gene expression in models for synovial joints

Correro-Shahgaldian

Colombo

Spencer

et al. 2011

Journal of Biomechanics

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“…To investigate these processes under defined conditions, in vitro models for injurious mechanical compression of the cartilage have been developed by a number of investigators [reviewed in Patwari et al (2001), Borrelli and Ricci (2004)]. These models may be useful for identifying the mechanical parameters of loading that are most responsible for damage to the cartilage matrix as well as for injury to the chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Relationship between Peak Stress and Proteoglycan Loss following Injurious Compression of Human Post-mortem Knee and Ankle Cartilage

Patwari

Cheng

Cole

et al. 2006

Biomech Model Mechanobiol

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While traumatic joint injuries are known to increase the risk of osteoarthritis (OA), the mechanism is not known. Models for injurious compression of cartilage may identify predictors of injury that suggest a clinical mechanism. We investigated the relationship between peak stress during compression and glycosaminoglycan (GAG) loss after injury for knee and ankle cartilages. Human cartilage explant disks were harvested post-mortem from the knee and ankle of three organ donors with no history of OA and subjected to injurious compression to 65% strain in uniaxial unconfined compression at 2 mm/s (400%/s). The GAG content of the conditioned medium was measured 3 days after injury. After injury of knee cartilage disks, damage was visible in 18 of 39 disks (36%). Three days after injury, the increase in GAG loss to the medium (GAG loss from injured disks minus GAG loss from location-matched uncompressed controls) was 1.5+/-0.3 microg/disk (mean +/- SEM). With final strain and compression velocity held constant, we observed that increasing peak stress during injury was associated with less GAG loss after injury (P<0.001). In contrast, ankle cartilage appeared damaged after injury in only 1 of 16 disks (6%), there was no increase in GAG loss (0.0+/-0.3 microg/disk), and no relationship between peak stress and increase in GAG loss was detected (P=0.51). By itself, increasing peak stress did not appear to be an important cause of GAG loss from human cartilage in our injurious compression model. However, we observed further evidence for differences in the response of knee and ankle cartilages to injury.

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“…Proteoglycans within the ECM of articular cartilage are the first macromolecules to respond to impact trauma. Changes in proteoglycan and collagen degradation are altered within days o f injury and remain like that for a substantial time (Patwari et al, 2001). A decrease in proteoglycan concentration faster than replenishment by new synthesis is thought to be the point at which this form of injury cannot be repaired and further impact will result in extra strain on other components of the ECM such as the collagen fibrils, resulting in degeneration of the articular cartilage (Buckwalter, 2002).…”

Section: Cell and Matrix Injuriesmentioning

confidence: 99%

“…The severity of this injury will be dependent on the size of the lesion, but invariably due to the avascular nature of the cartilage, no fibrin clot will be formed in a 6 0 Chapter 1 repair response and any attempt by local chondrocytes to up-regulate matrix synthesis will only be short term and will not result in filling of the defect (Beris et al, 2005;Buckwalter, 2002). Injury to cartilage alone is sufficient to cause OA and such injuries can result in progressive degeneration of the joint (Buckwalter et al, 1994;Patwari et al, 2001). …”

Section: Chondral Injuriesmentioning

confidence: 99%

Novel strategies for enhancing tissue integration in cartilage repair

Davies

Caterson

Duance

2004

Int J Experimental Path

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Introduction Articular cartilage is unable to initiate a spontaneous repair response when injured due to its avascular and aneural properties. Within adult cartilage, chondrocytes are entrapped within an extensive extracellular matrix and are unable to migrate to sights of injury to regulate tissue repair. Injury to this tissue therefore inevitably leads to degeneration of the cartilage and the development of degenerative diseases such as osteoarthritis. The surgical technique of autologous chondrocyte transplantation (ACT) was developed for the treatment of full‐thickness cartilage defects (Brittberg et al. 1994). Implantation of chondrocytes into the defect site repairs the injury site with a mixture of fibrocartilaginous and hyaline‐like tissue that poorly integrates with the existing cartilage and frequently degenerates with time. In this current study, we have developed an in vitro model to investigate methods for enhancing this integration and the development of a more biomechanically stable repair tissue. Materials and methods Bovine articular cartilage explants from the metacarpalphalangeal joint were experimentally injured using a stainless steel trephine and cultured for a period of 28 days. Autologous chondrocytes in an agarose suspension were injected into the interface region at the injury site. Media was collected and analysed for proteoglycan and collagen content using the DMMB and hydroxyproline assays, respectively. Matrix metalloproteinase (MMP) expression was also analysed using zymography and an adapted collagen fibril assay. Results Morphological analyses indicate attempts at repair and integration within both control and experimental treatment groups, although the presence of autologous chondrocytes appeared to amplify this repair response. Although not statistically significant, considerable differences in proteoglycan release between injured explants and the intact control group were seen. Collagen release into the media was only seen at day 28 within experimental cultures. An up‐regulation of MMP‐2 and MMP‐9 was seen within the experimental cultures compared to the controls. Preliminary data also suggest up‐regulation of collagenases in the experimental group when compared to controls. Discussion As seen with clinical ACT treatment, the presence of autologous chondrocytes appears to enhance repair and integration attempts; however, morphologically, this repair tissue appears to be fibrocartilaginous. Further analysis will establish whether the repair tissue is true hyaline cartilage and monitor the synthesis and turnover of macromolecules within the established culture system.

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In Vitro Models for Investigation of the Effects of Acute Mechanical Injury on Cartilage

Cited by 45 publications

References 37 publications

Coupling plowing of cartilage explants with gene expression in models for synovial joints

Coupling plowing of cartilage explants with gene expression in models for synovial joints

Analysis of the Relationship between Peak Stress and Proteoglycan Loss following Injurious Compression of Human Post-mortem Knee and Ankle Cartilage

Novel strategies for enhancing tissue integration in cartilage repair

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