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

Correro-Shahgaldian, Maria Rita; Colombo, Vera; Spencer, Nicholas D.; Weber, Franz E.; Imfeld, T; Gallo, Luigi M.

doi:10.1016/j.jbiomech.2011.06.021

Cited by 9 publications

(5 citation statements)

References 45 publications

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“…23,31 We performed a multiple regression analysis in order to determine what mechanical parameters influenced the gene expression. As found in previous studies, we found an increase in collagen type II and aggrecan expression with dynamic loading, 12,29 suggesting an attempt by the chondrocytes to adapt the ECM in response to the dynamic loading conditions. Fibronectin was the only gene that showed a significant correlation with multiple parameters; 66% of the fibronectin regulation in our model was correlated with strain (extrinsic) and the initial effective modulus (intrinsic).…”

Section: Discussionsupporting

confidence: 87%

A Model to Study Articular Cartilage Mechanical and Biological Responses to Sliding Loads

2015

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In physiological conditions, joint function involves continuously moving contact areas over the tissue surface. Such moving contacts play an important role for the durability of the tissue. It is known that in pathological joints these motion paths and contact mechanics change. Nevertheless, limited information exists on the impact of such physiological and pathophysiological dynamic loads on cartilage mechanics and its subsequent biological response. We designed and validated a mechanical device capable of applying simultaneous compression and sliding forces onto cartilage explants to simulate moving joint contact. Tests with varying axial loads (1 – 4 kg) and sliding speeds (1 – 20 mm/s) were performed on mature viable bovine femoral condyles to investigate cartilage mechanobiological responses. High loads and slow sliding speeds resulted in highest cartilage deformations. Contact stress and effective cartilage moduli increased with increasing load and increasing speed. In a pilot study, changes in gene expression of extracellular matrix proteins were correlated with strain, contact stress and dynamic effective modulus. This study describes a mechanical test system to study the cartilage response to reciprocating sliding motion and will be helpful in identifying mechanical and biological mechanisms leading to the initiation and development of cartilage degeneration.

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Section: Discussionsupporting

confidence: 87%

A Model to Study Articular Cartilage Mechanical and Biological Responses to Sliding Loads

2015

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“…That mechanical stimulus can have such an effect has been demonstrated by several studies. 47 , 48 Similarly, the expression of degradative enzymes was increased by pro-inflammatory cytokines, which further confirms that the culture conditions created for this study were similar to those found in OA. An increase of MMPs gene expression in bovine chondrocytes was also shown by Lv et al .…”

Section: Discussionsupporting

confidence: 82%

Biotribological Tests of Osteochondral Grafts after Treatment with Pro-Inflammatory Cytokines

et al. 2021

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Objective During osteoarthritis progression, cartilage degrades in a manner that influences its biomechanical and biotribological properties, while chondrocytes reduce the synthesis of extracellular matrix components and become apoptotic. This study investigates the effects of inflammation on cartilage under biomechanical stress using biotribological tests. Methods Bovine osteochondral grafts from five animals were punched out from the medial condyle and treated with or without pro-inflammatory cytokines (interleukin-1β [IL-1β], tumor necrosis factor-α [TNF-α], IL-6) for 2 weeks. After incubation, biotribological tests were performed for 2 hours (alternating 10 minutes test and pause respectively at 39°C, 180 N, 1 Hz, and 2 mm stroke). Before and after testing, the cartilage surface was imaged with a 3-dimensional microscope. During testing, the coefficient of friction (COF) was measured, while gene expression analysis and investigation of metabolic activity of chondrocytes were carried out after testing. Histological sections of the tissue and wear debris from the test fluid were also analyzed. Results After biotribological tests, surface cracks were found in both treated and untreated osteochondral grafts. In treated grafts, the COF increased, and the proteoglycan content in the cartilage tissue decreased, leading to structural changes. Chondrocytes from treated grafts showed increased expression of genes encoding for degradative enzymes, while cartilage-specific gene expression and metabolic activity exhibited no significant differences between treated and untreated groups. No measurable difference in the wear debris in the test fluid was found. Conclusions Treatment of osteochondral grafts with cytokines results in a significantly increased COF, while also leading to significant changes in cartilage proteoglycan content and cartilage matrix compression during biotribological tests.

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“…A previous study from our laboratory found that increasing tractional forces, induced by sliding and plowing, induced catabolic changes within the cartilage. 18 …”

Section: Introductionmentioning

confidence: 99%

Mechanical Loading of Cartilage Explants with Compression and Sliding Motion Modulates Gene Expression of Lubricin and Catabolic Enzymes

et al. 2015

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ObjectiveTranslation of the contact zone in articulating joints is an important component of joint kinematics, yet rarely investigated in a biological context. This study was designed to investigate how sliding contact areas affect cartilage mechanobiology. We hypothesized that higher sliding speeds would lead to increased extracellular matrix mechanical stress and the expression of catabolic genes.DesignA cylindrical Teflon indenter was used to apply 50 or 100 N normal forces at 10, 40, or 70 mm/s sliding speed. Mechanical parameters were correlated with gene expressions using a multiple linear regression model.ResultsIn both loading groups there was no significant effect of sliding speed on any of the mechanical parameters (strain, stress, modulus, tangential force). However, an increase in vertical force (from 50 to 100 N) led to a significant increase in extracellular matrix strain and stress. For 100 N, significant correlations between gene expression and mechanical parameters were found for TIMP-3 (r2 = 0.89), ADAMTS-5 (r2 = 0.73), and lubricin (r2 = 0.73).ConclusionsThe sliding speeds applied do not have an effect on the mechanical response of the cartilage, this could be explained by a partial attainment of the “elastic limit” at and above a sliding speed of 10 mm/s. Nevertheless, we still found a relationship between sliding speed and gene expression when the tissue was loaded with 100 N normal force. Thus despite the absence of speed-dependent mechanical changes (strain, stress, modulus, tangential force), the sliding speed had an influence on gene expression.

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

Cited by 9 publications

References 45 publications

A Model to Study Articular Cartilage Mechanical and Biological Responses to Sliding Loads

A Model to Study Articular Cartilage Mechanical and Biological Responses to Sliding Loads

Biotribological Tests of Osteochondral Grafts after Treatment with Pro-Inflammatory Cytokines

Mechanical Loading of Cartilage Explants with Compression and Sliding Motion Modulates Gene Expression of Lubricin and Catabolic Enzymes

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