The effect of running, strength, and vibration strength training on the mechanical, morphological, and biochemical properties of the Achilles tendon in rats

Compared with muscle or bone, there is a lack of information about the relationship between tendon adaptation and the applied loading characteristic. The purpose of the present study was to analyze the effect of different exercise modes characterized by very distinct loading patterns on the mechanical, morphological, and biochemical properties of the Achilles tendon. Sixty-four female Sprague-Dawley rats were divided into five groups: nonactive age-matched control (AMC; n = 20), voluntary wheel running (RT; n = 20), vibration strength-trained (LVST; n = 12), high-vibration strength-trained (HVST; n = 6), and high strength-trained (HST; n = 6) group. After a 12-wk-long experimental period, the Achilles tendon was tested mechanically and the cross-sectional area, the soleus and gastrocnemius muscle mass, and mRNA concentration of collagen I, collagen III, tissue inhibitor of metalloproteinase-1 (TIMP-1), transforming growth factor-β, connective tissue growth factor, and matrix metalloproteinase-2 was determined. Neither in the LVST nor in the HVST group could any adaptation of the Achilles tendon be detected, although the training had an effect on the gastrocnemius muscle mass in the LVST group ( P < 0.05). In the HST group, the highest creep was found, but the effect was more pronounced compared with the LVST group ( P < 0.05) than with the AMC group. That indicates that this was rather induced by the low muscle mass rather than by training. However, the RT group had a higher TIMP-1 mRNA concentration in the Achilles tendon in contrast to AMC group ( P < 0.05), which suggests that this exercise mode may have an influence on tendon adaptation.

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Uphill running improves rat Achilles tendon tissue mechanical properties and alters gene expression without inducing pathological changes

Journal of Applied Physiology ◽

10.1152/japplphysiol.00401.2012 ◽

2012 ◽

Vol 113 (5) ◽

pp. 827-836 ◽

Cited By ~ 39

Author(s):

K. M. Heinemeier ◽

D. Skovgaard ◽

M. L. Bayer ◽

K. Qvortrup ◽

A. Kjaer ◽

...

Keyword(s):

Gene Expression ◽

Mechanical Properties ◽

Growth Factor ◽

Achilles Tendon ◽

Glucose Uptake ◽

Transforming Growth Factor ◽

Achilles Tendinopathy ◽

Tissue Growth ◽

Tendon Tissue ◽

Collagen Iii

Overuse Achilles tendinopathy is a common and challenging problem in sports medicine. Little is known about the etiology of this disorder, and the development of a good animal model for overuse tendinopathy is essential for advancing insight into the disease mechanisms. Our aim was to test a previously proposed rat model for Achilles tendon overuse. Ten adult male Sprague-Dawley rats ran on a treadmill with 10° incline, 1 h/day, 5 days/wk (17–20 m/min) for 12 wk and were compared with 12 control rats. Histological, mechanical, and gene-expression changes were measured on the Achilles tendons after the intervention, and local tendon glucose-uptake was measured before and after the intervention with positron emission tomography. No differences were detected between runners and controls in tissue histology or in glucose uptake, indicating that tendon pathology was not induced. Greater tendon tissue modulus ( P < 0.005) and failure stress/body weight ( P < 0.02) in runners compared with controls further supported that tendons successfully adapted to uphill running. Several genes of interest were regulated after 12 wk of running. Expression of collagen III and insulin-like growth factor I was increased, while collagen I was unchanged, and decreases were seen in noncollagen matrix components (fibromodulin and biglycan), matrix degrading enzymes, transforming growth factor-β1, and connective tissue growth factor. In conclusion, the tested model could not be validated as a model for Achilles tendinopathy, as the rats were able to adapt to 12 wk of uphill running without any signs of tendinopathy. Improved mechanical properties were observed, as well as changes in gene-expression that were distinctly different from what is seen in tendinopathy and in response to short-term tendon loading.

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Decorin Interacts with Connective Tissue Growth Factor (CTGF)/CCN2 by LRR12 Inhibiting Its Biological Activity

Journal of Biological Chemistry ◽

10.1074/jbc.m110.189365 ◽

2011 ◽

Vol 286 (27) ◽

pp. 24242-24252 ◽

Cited By ~ 72

Author(s):

Cecilia Vial ◽

Jaime Gutiérrez ◽

Cristian Santander ◽

Daniel Cabrera ◽

Enrique Brandan

Keyword(s):

Biological Activity ◽

Growth Factor ◽

Connective Tissue ◽

Connective Tissue Growth Factor ◽

Core Protein ◽

Tissue Growth ◽

Collagen Iii ◽

Fibrotic Disorders ◽

Leucine Rich Repeats

Fibrotic disorders are the end point of many chronic diseases in different tissues, where an accumulation of the extracellular matrix occurs, mainly because of the action of the connective tissue growth factor (CTGF/CCN2). Little is known about how this growth factor activity is regulated. We found that decorin null myoblasts are more sensitive to CTGF than wild type myoblasts, as evaluated by the accumulation of fibronectin or collagen III. Decorin added exogenously negatively regulated CTGF pro-fibrotic activity and the induction of actin stress fibers. Using co-immunoprecipitation and in vitro interaction assays, decorin and CTGF were shown to interact in a saturable manner with a Kd of 4.4 nm. This interaction requires the core protein of decorin. Experiments using the deletion mutant decorin indicated that the leucine-rich repeats (LRR) 10–12 are important for the interaction with CTGF and the negative regulation of the cytokine activity, moreover, a peptide derived from the LRR12 was able to inhibit CTGF-decorin complex formation and CTGF activity. Finally, we showed that CTGF specifically induced the synthesis of decorin, suggesting a mechanism of autoregulation. These results suggest that decorin interacts with CTGF and regulates its biological activity.

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No effect of aging on skeletal muscle insulin-like growth factor mRNAs

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.269.5.r1183 ◽

1995 ◽

Vol 269 (5) ◽

pp. R1183-R1188 ◽

Cited By ~ 3

Author(s):

M. T. Hamilton ◽

D. R. Marsh ◽

D. S. Criswell ◽

W. Lou ◽

F. W. Booth

Keyword(s):

Skeletal Muscle ◽

Growth Factor ◽

Gastrocnemius Muscle ◽

Muscle Size ◽

Total Protein Content ◽

Ribonuclease Protection Assay ◽

Insulin Like Growth Factor ◽

Mrna Concentration ◽

Igf I ◽

Old Rats

This study examined the hypothesis that during aging insulin-like growth factor (IGF) mRNAs are reduced in skeletal muscle. IGF-I, IGF-II, and IGF-binding protein-5 (IGFBP-5) mRNAs were measured with a ribonuclease protection assay in the gastrocnemius of specific pathogen-free Fischer-344 rats. We hypothesized that IGF-I, IGF-II, and IGFBP-5 mRNA concentration (normalized to 18S RNA) in the gastrocnemius muscle of growing animals (3 mo) would be downregulated in a coordinated manner with muscle size during aging-associated atrophy. As indicated by muscle wet weight and total protein content, the gastrocnemius muscle was growing in the 3-mo group (P < 0.01 smaller compared with 12 mo), fully developed at 12 mo, and was atrophied at 24 mo of age (P < 0.05 compared with 12 mo). IGF-I mRNA concentration in the gastrocnemius of 12- and 24-mo-old rats was 39-49% less than in 3-mo-old rats (P < 0.05). Contrary to our hypothesis, there was not a significant skeletal muscle IGF-I mRNA difference between middle age (12 mo) and senescence (24 mo). Thus IGF-I mRNA changed during maturation (3-12 mo) but not during aging (12-24 mo). Skeletal muscle IGF-II mRNA concentration was not different among 3-, 12-, and 24-mo-old animals. Furthermore, animal age did not have an effect on IGFBP-5 mRNA concentration. We conclude that the aging-associated atrophy of skeletal muscle is not caused by altered pretranslational regulation of IGF-I, IGF-II, or IGFBP-5 in skeletal muscle.

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Adaptation of mechanical, morphological and biochemical properties of the rat achilles tendon to running, strength and vibration strength training

Journal of Biomechanics ◽

10.1016/s0021-9290(06)83114-3 ◽

2006 ◽

Vol 39 ◽

pp. S58

Author(s):

K. Legerlotz ◽

P. Schjerling ◽

H. Langberg ◽

G.-P. Brüggemann ◽

A. Niehoff

Keyword(s):

Strength Training ◽

Achilles Tendon ◽

Biochemical Properties ◽

Vibration Strength

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Ocular surface cytokine profile in chronic Stevens-Johnson syndrome and its response to mucous membrane grafting for lid margin keratinisation

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2017-310373 ◽

2017 ◽

Vol 102 (2) ◽

pp. 169-176 ◽

Cited By ~ 12

Author(s):

Srividya Gurumurthy ◽

Geetha Iyer ◽

Bhaskar Srinivasan ◽

Shweta Agarwal ◽

Narayanasamy Angayarkanni

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Mucous Membrane ◽

Ocular Surface ◽

Transforming Growth Factor ◽

Tissue Growth ◽

Stevens Johnson Syndrome ◽

Gm Csf ◽

Johnson Syndrome ◽

Collagen Iii

BackgroundTo study the tear cytokine and the conjunctival and oral mucosal marker profile in chronic ocular Stevens-Johnson syndrome (SJS) and their alteration following mucous membrane grafting (MMG) for lid margin keratinisation (LMK).MethodsIn a 1-year prospective study, SJS cases (n=25) and age-matched/sex-matched healthy controls (n=25) were recruited. Tear specimen (Schirmer’s strip), conjunctival and oral mucosal imprints were collected from controls and SJS cases pre-MMG and post-MMG (at first follow-up, n=17). Tear cytokines were profiled using 27-bioplex array. Transforming growth factor-beta (TGF-β)-mediated extracellular matrix changes in conjunctival and oral mucosal cells were analysed by gene expression studies. 30ResultsTear cytokine profiling of chronic SJS cases at pre-MMG stage revealed significant upregulation of cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, IL-1β, monocyte chemoattractant protein-1, IL-15, IL-2, IL-17A and basic fibroblast growth factor (bFGF) with downregulation of IP-10 (interferon gamma-induced protein 10), tumour necrosis factor-α, interferon-γ, IL-10, vascular endothelial growth factor, regulated upon activation normal T-cell expressed and secreted (RANTES), IL-7, IL-12p70 and IL-13, with maximal increase in GM-CSF and maximal downregulation of IP-10, respectively. Of these, IL-2, IL-15, bFGF and IL-17A showed significant correlation with disease severity, pre-MMG. Conjunctival cells pre-MMG showed increase in TGF-β1, TGF-βRII, connective tissue growth factor and collagen-III gene expression by 10, 67, 173 and 184 folds, respectively, which dropped to 1.3, 11, 13.5 and 19 folds correspondingly, post-MMG. However, their expressions in oral mucosa were negligible.ConclusionA proinflammatory, profibrotic, antiapoptotic ocular surface milieu characterises chronic ocular SJS. IP-10, an antifibrotic cytokine was noted to be maximally downregulated, unlike in other forms of chronic dry eye disease. The alterations in the ocular surface are seen to reverse largely with MMG for LMK.

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Growth Factor-Reinforced ECM Fabricated from Chemically Hypoxic MSC Sheet with Improved In Vivo Wound Repair Activity

BioMed Research International ◽

10.1155/2017/2578017 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Hui-Cong Du ◽

Lin Jiang ◽

Wen-Xin Geng ◽

Jing Li ◽

Rui Zhang ◽

...

Keyword(s):

Wound Healing ◽

Growth Factor ◽

Wound Repair ◽

Cost Effective ◽

Tissue Growth ◽

Wound Management ◽

Skin Defect ◽

Therapeutic Benefits ◽

Collagen Iii

MSC treatment can promote cutaneous wound repair through multiple mechanisms, and paracrine mediators secreted by MSC are responsible for most of its therapeutic benefits. Recently, MSC sheet composed of live MSCs and their secreted ECMs was reported to promote wound healing; however, whether its ECM alone could accelerate wound closure remained unknown. In this study, Nc-ECM and Cc-ECM were prepared from nonconditioned and CoCl2-conditioned MSC sheets, respectively, and their wound healing properties were evaluated in a mouse model of full-thickness skin defect. Our results showed that Nc-ECM can significantly promote wound repair through early adipocyte recruitment, rapid reepithelialization, enhanced granulation tissue growth, and augmented angiogenesis. Moreover, conditioning of MSC sheet with CoCl2 dramatically enriched its ECM with collagen I, collagen III, TGF-β1, VEGF, and bFGF via activation of HIF-1α and hence remarkably improved its ECM’s in vivo wound healing potency. All the Cc-ECM-treated wounds completely healed on day 7, while Nc-ECM-treated wounds healed about 85.0%±8.6%, and no-treatment wounds only healed 69.8%±9.6% (p<0.05). Therefore, we believe that such growth factor-reinforced ECM fabricated from chemically hypoxic MSC sheet has the potential for clinical translation and will lead to a MSC-derived, cost-effective, bankable biomaterial for wound management.

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miR-29a is a Potential Protective Factor for Fibrogenesis in Gluteal Muscle Contracture

Physiological Research ◽

10.33549/physiolres.934295 ◽

2020 ◽

pp. 467-479

Author(s):

R ZHOU ◽

S REN ◽

C LI ◽

X ZHANG ◽

W ZHANG

Keyword(s):

Growth Factor ◽

Early Diagnosis ◽

Cell Viability ◽

Tissue Growth ◽

Gluteal Muscle ◽

Muscle Contracture ◽

Gluteal Muscle Contracture ◽

Potential Biomarker ◽

Collagen Iii ◽

Tgf Β1

Circulating miRNAs have been proposed as the effective diagnostic biomarkers for muscular fibrosis-associated diseases. However, circulating biomarkers for early diagnosis of contracture muscles are limited in gluteal muscle contracture (GMC) patients. Here we sought to explore the abnormally expressed miRNAs in plasma and contraction bands of GMC patients. The results showed miR-29a-3p expression in plasma and contraction bands tissue was significantly reduced in GMC patients compared with normal control. Cell viability and levels of proliferation-associated protein cyclin D1 and cyclin-dependent-kinase 2 (CDK2) were powerfully inhibited by miR-29a mimics and enhanced by miR-29a inhibitor compared with negative control. Furthermore, miR-29a mimics effectively impeded, while miR-29a inhibitor enhanced the expression of collagen I and collagen III, followed by the secretion of transforming growth factor β1 (TGF-β1), TGF-β3 and connective tissue growth factor (CTGF) in primary human contraction bands (CB) fibroblasts. The miR-29a-3p negatively regulated the expression of TGF-β1 through binding to the 3′ UTR region of SERPINH1 (encoding heat shock protein HSP47), but had no effect on Smad2 activity. The miR-29a-3p was inversely correlated with HSP47 in contraction bands tissue from GMC patients. Collectively, miR-29a was notably depressed and regulated cell viability and fibrosis by directly targeting HSP47 in GMC, which suggest that circulating miR-29a might be a potential biomarker for early diagnosis and provides a novel therapeutic target for GMC.

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