Dataset Information

Simvastatin and atorvastatin reduce the mechanical properties of tendon constructs in vitro and introduce catabolic changes in the gene expression pattern.

ABSTRACT: Treatment with lipid-lowering drugs, statins, is common all over the world. Lately, the occurrence of spontaneous tendon ruptures or tendinosis have suggested a negative influence of statins upon tendon tissue. But how statins might influence tendons is not clear. In the present study, we investigated the effect of statin treatment on mechanical strength, cell proliferation, collagen content and gene expression pattern in a tendon-like tissue made from human tenocytes in vitro. Human tendon fibroblasts were grown in a 3D tissue culture model (tendon constructs), and treated with either simvastatin or atorvastatin, low or high dose, respectively, for up to seven days. After seven days of treatment, mechanical testing of the constructs was performed. Collagen content and cell proliferation were also determined. mRNA levels of several target genes were measured after one or seven days. The maximum force and stiffness were reduced by both statins after 7 days (p<0.05), while the cross sectional area was unaffected. Further, the collagen content was reduced by atorvastatin (p = 0.01) and the cell proliferation rate was decreased by both types of statins (p<0.05). Statin treatment also introduced increased mRNA levels of MMP-1, MMP-3, MMP-13, TIMP-1 and decreased levels of collagen type 1 and 3. In conclusion, statin treatment appears to have a negative effect on tendon matrix quality as seen by a reduced strength of the tendon constructs. Further, activated catabolic changes in the gene expression pattern and a reduced collagen content indicated a disturbed balance in matrix production of tendon due to statin administration.

SUBMITTER: Eliasson P

PROVIDER: S-EPMC5339395 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Simvastatin and atorvastatin reduce the mechanical properties of tendon constructs in vitro and introduce catabolic changes in the gene expression pattern.

Eliasson Pernilla P Svensson Rene B RB Giannopoulos Antonis A Eismark Christian C Kjær Michael M Schjerling Peter P Heinemeier Katja M KM

PloS one 20170306 3

Treatment with lipid-lowering drugs, statins, is common all over the world. Lately, the occurrence of spontaneous tendon ruptures or tendinosis have suggested a negative influence of statins upon tendon tissue. But how statins might influence tendons is not clear. In the present study, we investigated the effect of statin treatment on mechanical strength, cell proliferation, collagen content and gene expression pattern in a tendon-like tissue made from human tenocytes in vitro. Human tendon fibr ...[more]

PMID: 28264197

Similar Datasets

Project description:Pancreatic ductal adenocarcinoma (PDAC) is almost universally fatal, in large part due to a protective fibrotic barrier generated by tumor-associated stromal (TAS) cells. This barrier is thought to promote cancer cell survival and confounds attempts to develop effective therapies. We present a 3D in vitro system that replicates the mechanical properties of the PDAC microenvironment, representing an invaluable tool for understanding the biology of the disease. Mesoscale indentation quantified viscoelastic metrics of resected malignant tumors, inflamed chronic pancreatitis regions, and histologically normal tissue. Both pancreatitis (2.15?±?0.41?kPa, Mean?±?SD) and tumors (5.46?±?3.18?kPa) exhibit higher Steady-State Modulus (SSM) than normal tissue (1.06?±?0.25?kPa; p?<?.005). The average viscosity of pancreatitis samples (63.2?±?26.7?kPa·s) is significantly lower than that of both normal tissue (252?±?134?kPa·s) and tumors (349?±?222?kPa·s; p?<?.005). To mimic this remodeling behavior, PDAC and TAS cells were isolated from human PDAC tumors. Conditioned medium from PDAC cells was used to culture TAS-embedded collagen hydrogels. After 7?days, TAS-embedded gels in control medium reached SSM (1.45?±?0.12?kPa) near normal pancreas, while gels maintained with conditioned medium achieved higher SSM (3.38?±?0.146?kPa) consistent with tumors. Taken together, we have demonstrated an in vitro system that recapitulates in vivo stiffening of PDAC tumors. In addition, our quantification of viscoelastic properties suggests that elastography algorithms incorporating viscosity may be able to more accurately distinguish between pancreatic cancer and pancreatitis. STATEMENT OF SIGNIFICANCE:Understanding tumor-stroma crosstalk in pancreatic ductal adenocarcinoma (PDAC) is challenged by a lack of stroma-mimicking model systems. To design appropriate models, pancreatic tissue must be characterized with a method capable of evaluating in vitro models as well. Our indentation-based characterization tool quantified the distinct viscoelastic signatures of inflamed resections from pancreatitis, tumors from PDAC, and otherwise normal tissue to inform development of mechanically appropriate engineered tissues and scaffolds. We also made progress toward a 3D in vitro system that recapitulates mechanical properties of tumors. Our in vitro model of stromal cells in collagen and complementary characterization system can be used to investigate mechanisms of cancer-stroma crosstalk in PDAC and to propose and test innovative therapies.

Project description:IntroductionThe effect of chronic patellar tendinopathy on tissue function and integrity is currently unclear and underinvestigated. The aim of this cohort comparison was to examine morphological, material, and mechanical properties of the patellar tendon and to extend earlier findings by measuring the ability to store and return elastic energy in symptomatic tendons.MethodsSeventeen patients with chronic (>3 months, VISA-P < 80), inferior pole patellar tendinopathy (24 ± 4 years; male = 12, female = 5) were carefully matched to controls (25 ± 3 years) for training status, pattern, and history of loading of the patellar tendon. Individual knee extension force, patellar tendon stiffness, stress, strain, Young's modulus, hysteresis, and energy storage capacity, were obtained with combined dynamometry, ultrasonography, magnetic resonance imaging, and electromyography.ResultsAnthropometric parameters did not differ between groups. VISA-P scores ranged from 28 to 78 points, and symptoms had lasted from 10 to 120 months before testing. Tendon proximal cross-sectional area was 61% larger in the patellar tendinopathy group than in the control group. There were no differences between groups in maximal voluntary isometric knee extension torque (p = 0.216; d < -0.31) nor in tensile tendon force produced during isometric ramp contractions (p = 0.185; d < -0.34). Similarly, tendon strain (p = 0.634; d < 0.12), hysteresis (p = 0.461; d < 0.18), and strain energy storage (p = 0.656; d < 0.36) did not differ between groups. However, patellar tendon stiffness (-19%; p = 0.007; d < -0.74), stress (-27%; p< 0.002; d < -0.90) and Young's modulus (-32%; p = 0.001; d < -0.94) were significantly lower in tendinopathic patients compared to healthy controls.DiscussionIn this study, we observed lower stiffness in affected tendons. However, despite the substantial structural and histological changes occurring with tendinopathy, the tendon capacity to store and dissipate energy did not differ significantly.

Dataset Information

Simvastatin and atorvastatin reduce the mechanical properties of tendon constructs in vitro and introduce catabolic changes in the gene expression pattern.

Publications

Simvastatin and atorvastatin reduce the mechanical properties of tendon constructs in vitro and introduce catabolic changes in the gene expression pattern.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets