scholarly journals Synergist ablation induces rapid tendon growth through the synthesis of a neotendon matrix

2014 ◽  
Vol 117 (11) ◽  
pp. 1287-1291 ◽  
Author(s):  
Jonathan P. Gumucio ◽  
Anthony C. Phan ◽  
David G. Ruehlmann ◽  
Andrew C. Noah ◽  
Christopher L. Mendias
Keyword(s):  
Mechanical Loading ◽  
Type I Collagen ◽  
Fluorescent Microscopy ◽  
Type I ◽  
Fibroblast Cells ◽  
Cellular Mechanisms ◽  
Fast Green ◽  
Cross Sectional ◽  
Plantaris Tendon ◽  
Insight Into

Mechanical loading can increase tendon cross-sectional area (CSA), but the mechanisms by which this occurs are largely unknown. To gain a greater understanding of the cellular mechanisms of adult tendon growth in response to mechanical loading, we used a synergist ablation model whereby a tenectomy of the Achilles tendon was performed to induce growth of the synergist plantaris tendon. We hypothesized that after synergist ablation progenitor cells in the epitenon would proliferate and increase the size of the existing tendon matrix. Adult male mice were subjected to a bilateral Achilles tenectomy, and plantaris tendons were isolated from mice at 0, 2, 7, 14, and 28 days after surgery. Tendons were sectioned stained with either fast green and hematoxylin, prepared for fluorescent microscopy, or prepared for gene expression of scleraxis and type I collagen. After overload, there was a dramatic increase in total CSA of tendons, whereas the size of the original tendon matrix was not changed. Growth primarily occurred through the formation of a neotendon matrix between the original tendon and the epitenon, and contained cells that were proliferative and scleraxis positive. Additionally, an initial expansion of fibroblast cells occurred before the synthesis of new extracellular matrix. Fibroblasts in the original tendon did not re-enter the cell cycle. The results from this study provide new insight into the mechanisms of tendon growth, indicate tendon consists mostly of postmitotic cells, and that growth of tendon primarily occurs from the most superficial layers outward.

scholarly journals Musculoskeletal Outcomes from Chronic High-Speed, High-Impulse Resistance Exercise

2018 ◽  
Vol 39 (10) ◽  
pp. 791-801 ◽  
Author(s):  
John Caruso ◽  
Michael Voor ◽  
Jason Jaggers ◽  
T. Symons ◽  
Jeremy Stith ◽  
...  
Keyword(s):  
Mechanical Loading ◽  
High Speed ◽  
Type I Collagen ◽  
Training Session ◽  
Knee Extension ◽  
Type I ◽  
Before And After ◽  
Force Peak ◽  
Blood Marker ◽  
Hip Extension

AbstractWhile bones and muscles adapt to mechanical loading, it appears that very specific types of stimuli must be applied to achieve osteogenesis. Our study assessed musculoskeletal outcomes to 30 training sessions on an Inertial Exercise Trainer (Newnan, GA). Subjects (n=13) performed workouts with their left leg, while their right served as an untreated control. Workouts entailed three 60-s sets each of knee extension, hip extension and calf press exercises, separated by 90-s rests. Before and after the 30 training sessions, subjects underwent strength tests (knee and ankle extensors of both legs), DEXA scans (hip, knee and ankles of both legs), and blood draws. After 30 training sessions 2×2 ANOVAs showed left leg peak torques rose significantly. 2×2 ANCOVAs, with bone scan area as a covariate, showed significant left leg calcaneal bone mineral content (+29%) and density (+33%) increases after 30 training sessions. A significant decline in C-terminal telopeptides of type I collagen, a blood marker of bone resorption, also occurred after 30 training sessions. The Inertial Exercise Trainer’s large volume of training session repetitions elicited high peak force, peak acceleration and impulses that likely provided a mechanical loading stimulus that evoked calcaneal accretion.

Osteogenesis imperfecta in Three Dogs from a Single Litter

2000 ◽  
Vol 13 (01) ◽  
pp. 23-27
Author(s):  
J. J. deHaan ◽  
J. N. Peck ◽  
Bonnie Campbell ◽  
Pamela Ginn ◽  
Lynette Phillips ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Type I ◽  
Fibroblast Cells ◽  
Pathological Fractures ◽  
Presumptive Diagnosis ◽  
Cultured Skin ◽  
Pathologic Features ◽  
History Of ◽  
Collagen Analysis

SummaryThree American Cream puppies from a litter of six were admitted for evaluation and treatment of lameness caused by multiple pathological fractures. Because of a poor prognosis, all three of the affected dogs were ultimately euthanatized. Based on the histopathological findings of the bones and a collagen analysis from cultured skin fibroblast cells which confirmed the presence of abnormal type I collagen, the presumptive diagnosis was osteogenesis imperfecta. In humans, more than 90% of the cases of osteogenesis imperfecta are caused by defects in type I collagen (11). Osteogenesis imperfecta has rarely been described in animals and none of the previous reports document the disease in more than one dog from a single litter.Three American Cream puppies from a litter of six developed multiple pathologic features without a history of trauma. A diagnosis of osteogenesis imperfecta was made based on histopathology and results of type I collagen analysis from cultured skin fibroblasts.

Type I collagen gene regulation and the molecular pathogenesis of cirrhosis

1993 ◽  
Vol 264 (4) ◽  
pp. G589-G595 ◽  
Author(s):  
D. A. Brenner ◽  
J. Westwick ◽  
M. Breindl
Keyword(s):  
Protein Interactions ◽  
Type I Collagen ◽  
Collagen Type ◽  
Collagen Type I ◽  
Molecular Pathogenesis ◽  
Matrix Proteins ◽  
Type I ◽  
And Function ◽  
Collagen Genes ◽  
Insight Into

Cirrhosis is characterized by an increased deposition of extracellular matrix proteins, including type I collagen. Type I collagen is a product of two genes, alpha 1(I) and alpha 2(I), which are generally coordinately regulated. Since expression of type I collagen genes is increased during cirrhosis, understanding the structure and function of the regulatory components of the type I collagen genes should provide insight into the molecular pathogenesis of cirrhosis. This review will analyze the collagen alpha 1(I) gene with respect to chromatin structure, DNA methylation, regulation by agonists, and DNA-protein interactions.

Abstract 129: Human Mesenchymal Stem Cells Augment Contractile Function of Human Engineered Cardiac Tissues

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Timothy Cashman ◽  
Irene C Turnbull ◽  
Ioannis Karakikes ◽  
Jose Da Silva ◽  
Joshua M Hare ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Type I Collagen ◽  
High Efficiency ◽  
Contractile Function ◽  
Embryonic Stem ◽  
Type I ◽  
Cross Sectional ◽  
Cardiac Tissues ◽  
Twitch Force

Mesenchymal stem cells (MSC) have demonstrated efficacy for improving cardiomyocyte (CM) function in vitro, in vivo and in clinical trials, but the mechanism of this enhancement remains elusive. The objective of this study was to test the hypothesis that human engineered cardiac tissues (hECT) offer a viable model system to investigate the effects of human MSC on CM contractile function. Human CM (hCM) were produced from embryonic stem cells (hESC, H7 line) using a small-molecule based differentiation approach. Blebbistatin and BMP4 were added to hESC suspended in StemPro34 differentiation media for 24 h, followed by BMP4 and Activin A to day 4.5, followed by addition of IWR-1 Wnt inhibitor for at least 4 days. To create hECT, approximately 1 million hCM were mixed with 2.0 mg/ml bovine type I collagen and 0.9 mg/ml Matrigel, and pipetted into a mold fabricated from polydimethylsiloxane with integrated cantilever end-posts. To model hMSC cell therapy, two types of hECT were created: hCM-only control hECT, and hMSC-CM hybrid hECT containing hCM mixed with 5-10% of human bone marrow-derived MSC. Over several days in culture, the hECT self-assembled and started beating; end-post deflection was tracked in real time to compute twitch force using beam theory. Human CMs were produced with high efficiency (>70% cTnT+) with a predominantly ventricular phenotype (MLC2v+). Resulting hECTs exhibited spontaneous beating (1.3±0.4 Hz), cellular alignment, registered sarcomeres, and expression of cardiac specific genes cTnT, α-MHC, β-MHC and SERCA2a. After 11±2 days in culture, developed stress (force/area) was over 10-fold higher in hMSC-CM hybrid tissues (0.27±0.048 mN/mm 2 ) compared to hCM-only controls (0.02±0.006 mN/mm 2 ; p=0.04, n=5 per group). This reflected significantly greater twitch force (0.11±0.004 mN vs 0.033±0.016 mN, p=0.016) and smaller cross-sectional area (0.19±0.12 mm 2 vs 0.49±0.10 mm 2 ; p=0.003) in hMSC-CM hybrid vs hCM-only hECT. In conclusion, human ECT offer a novel system to study MSC-CM interactions. The findings suggest hMSC supplementation improves contractility compared to CM-only hECT. Investigating the mechanisms of hMSC-mediated enhancement of hECT function may yield insights into MSC-based therapies for cardiac regeneration.

scholarly journals Association between serum vitamin B6concentration and risk of osteoporosis in the middle-aged and older people in China: a cross-sectional study

BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e028129 ◽  
Author(s):  
Jing Wang ◽  
Lin Chen ◽  
Yan Zhang ◽  
Chen-guang Li ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Type I Collagen ◽  
Bone Turnover Marker ◽  
Serum Vitamin ◽  
Type I ◽  
Hormone Concentration ◽  
Mineral Density ◽  
Cross Sectional ◽  
25 Hydroxy Vitamin D

ObjectiveTo determine the relationship between serum vitamin B6(Vit B6) concentration and the status of bone mineral density and identify the relationship between serum Vit B6 and bone metabolism parameters in middle-aged and older people in China.DesignThe present study was a cross-sectional study within the framework of an ongoing prospective population-based cohort study.Setting and participantsA total of 1829 residents (men ≥50 years and women ≥45 years) from two subdistricts were recruited from July 2015 to February 2016 in Shanghai, China.MeasuresRecruited residents were grouped (control, osteopenia and osteoporosis) according to their lumbar spine bone mineral density, measured through dual-energy X-ray absorptiometry. Serum Vit B6concentrations, bone turnover marker concentrations and calcium and phosphorus metabolism parameters were assessed.ResultsNo significant linear trend between serum Vit B6concentrations and lumbar bone mass was observed in the men. In the women, the average osteoporosis risk was 61% higher at serum Vit B6concentrations of <19.2 μg/L than at those of >26.9 μg/L (OR 1.61, 95% CI 1.00 to 2.58). However, there was no significance after controlling of serum 25-hydroxy-vitamin D concentration and parathyroid hormone concentration, respectively. In the osteoporotic women, the serum Vit B6concentration was significantly negatively correlated to concentrations of bone turnover marker including N-terminal propeptide of type I collagen, β-C-terminal telopeptide of type I collagen and osteocalcin. It was also positively related to the serum 25-hydroxy-vitamin D concentration and inversely related to the serum parathyroid hormone concentration.ConclusionsA relatively low serum Vit B6concentration, even in the normal range, may be a risk factor for osteoporosis in postmenopausal women, which is dependent on serum 25-hydroxy-vitamin D concentration and parathyroid hormone concentration.Trial registration numberNCT02958020; Post-results.

Gallium nitrate increases type I collagen and fibronectin mRNA and collagen protein levels in bone and fibroblast cells

1993 ◽  
Vol 52 (4) ◽  
pp. 396-403 ◽  
Author(s):  
Richard S. Bockman ◽  
Peter T. Guidon ◽  
Lydia C. Pan ◽  
Roberto Salvatori ◽  
Alan Kawaguchi
Keyword(s):  
Type I Collagen ◽  
Gallium Nitrate ◽  
Type I ◽  
Fibroblast Cells ◽  
Protein Levels ◽  
Collagen Protein ◽  
Fibronectin Mrna

scholarly journals Influence of Demographic Factors and Sport Type on Growth Hormone-Responsive Markers in Elite Athletes

2006 ◽  
Vol 91 (11) ◽  
pp. 4424-4432 ◽  
Author(s):  
A. E. Nelson ◽  
C. J. Howe ◽  
T. V. Nguyen ◽  
K.-C. Leung ◽  
G. J. Trout ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Elite Athletes ◽  
Significant Negative Correlation ◽  
Type I ◽  
Cross Sectional ◽  
Age And Gender ◽  
Igf I ◽  
And Gender ◽  
Collagen Markers ◽  
Igfbp 3

Abstract Context: GH-responsive markers of the IGF system and of collagen turnover hold promise as the basis of a GH doping test. Objective: The purpose of this study was to determine the influence of age, gender, body mass index (BMI), ethnicity, and sporting type on GH-responsive serum markers in a large cohort of elite athletes from different ethnic backgrounds. Design: The study was designed as a cross-sectional study. Participants: A total of 1103 elite athletes (699 males, 404 females), aged 22.2 ± 5.2 yr, from 12 countries and 10 major sporting categories participated in this study. Main Outcome Measures: Serum IGF-I, IGF binding protein-3 (IGFBP-3), acid labile subunit (ALS), and collagen markers [N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (ICTP), N-terminal propeptide of type III procollagen (PIIINP)] were measured. Results: There was a significant negative correlation (r = −0.14 to −0.58, P &lt; 0.0005) between age and each of the GH-responsive markers. Serum IGF-I, IGFBP-3, and ALS were all lower (P &lt; 0.05), whereas the collagen markers PINP, ICTP, and PIIINP were higher (P &lt; 0.05) in men than in women. Multiple regression analysis indicated that age, gender, BMI, and ethnicity accounted for 23–54% of total between-subject variability of the markers. Age and gender cumulatively accounted for 91% of the attributable variation of IGF-I and more than 80% for PINP, ICTP, and PIIINP. Gender exerted the greatest effect on ALS (48%), and BMI accounted for less than 12% attributable variation for all markers. The influence of ethnicity was greatest for IGFBP-3 and ALS; however, for the other markers, it accounted for less than 6% attributable variation. Analysis of 995 athletes indicated that sporting type contributed 5–19% of attributable variation. Conclusions: Age and gender were major determinants of variability of GH-responsive markers except for IGFBP-3 and ALS. Ethnicity is unlikely to confound the validity of a GH doping test based on IGF-I and these collagen markers.

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