Exercise-dependent IGF-I, IGFBPs, and type I collagen changes in human peritendinous connective tissue determined by microdialysis

2007 ◽  
Vol 102 (1) ◽  
pp. 214-220 ◽  
Author(s):  
Jens L. Olesen ◽  
Katja M. Heinemeier ◽  
Carsten Gemmer ◽  
Michael Kjær ◽  
Allan Flyvbjerg ◽  
...  
Keyword(s):  
Mechanical Loading ◽  
Collagen Synthesis ◽  
Acute Exercise ◽  
Type I Collagen ◽  
Exercise Group ◽  
Control Group ◽  
Local Concentration ◽  
Type I ◽  
Collagen Production ◽  
Igf I

Microdialysis studies indicate that mechanical loading of human tendon during exercise elevates type I collagen production in tendon. However, the possibility that the insertion of microdialysis fibers per se may increase the local collagen production due to trauma has not been explored. Insulin-like growth factor I (IGF-I) and its binding proteins (IGFBPs), which are known to stimulate collagen production in animal tendons, may regulate the translation of mechanical loading to collagen synthesis. Systemic and tissue levels of IGF-I, IGFBP, and type I collagen metabolism markers [procollagen I COOH-terminal propeptide (PICP) and COOH-terminal telopeptide of type I collagen] were measured by microdialysis in peritendinous tissue of the human Achilles tendon in an exercise group (performing a 36-km run, n = 6) and a control group (no intervention, n = 6). An increase in local PICP concentration was seen in both groups after 72 h and stayed elevated in the exercise group at 96 h ( P < 0.05). IGFBP-1 in both serum and dialysate increased in the exercise group immediately after exercise ( P < 0.05), whereas IGFBP-3 decreased systemically ( P < 0.05). Elevation of local IGFBP-4 was observed in both the control and exercise groups after 48 h ( P < 0.05). Total IGF-I did not change in locally or systemically in either group. Our results indicate an increased local production of PICP in human peritendinous tissue in response to prolonged mechanical loading with part of the increase due to trauma from the sampling technique. Care must therefore be emphasized to minimize the numbers of insertions with microdialysis. We demonstrated an elevation of IGFBP-1 both systemically and peritendinously in response to prolonged acute exercise. The local increased collagen synthesis was preceded by an elevation of local concentration of IGFBP-4, suggesting that IGFBP-4 may have a key role in the IGF-axis effect on the human collagen synthesis in vivo.

Effects of transdermal estrogen on collagen turnover at rest and in response to exercise in postmenopausal women

2012 ◽  
Vol 113 (7) ◽  
pp. 1040-1047 ◽  
Author(s):  
J. Pingel ◽  
H. Langberg ◽  
D. Skovgård ◽  
S. Koskinen ◽  
A. Flyvbjerg ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Postmenopausal Women ◽  
Acute Exercise ◽  
Type I Collagen ◽  
Control Period ◽  
Vastus Lateralis Muscle ◽  
Type I ◽  
Relative Role ◽  
Igf I ◽  
Transdermal Estrogen

Menopause is associated with loss of collagen content in the skin and tendon as well as accumulation of noncontractile tissue in skeletal muscle. The relative role of hormones and physical activity on these changes is not known. Accordingly, in a randomized, controlled, crossover study we investigated effects of transdermal estrogen replacement therapy (ERT) on type I collagen synthesis in tendon and skeletal muscle in 11 postmenopausal women. Patches with estrogen (Evorel) were placed on the skin above the patellar tendons and compared with no patch (control period). On day 2 all subjects performed one-legged exercise, and thereafter the exercised leg (EX leg) was compared with the nonexercised leg (Rest leg). Microdialysis catheters were placed in front of the patellar tendons and in the vastus lateralis muscle of both legs at days 3 and 5. The collected dialysate was analyzed for procollagen type I NH2-terminal propeptide (PINP), insulin-like growth factor I (IGF-I), and interleukin-6 (IL-6). Neither loading (Rest leg vs. EX leg) nor treatment (control vs. ERT) influenced peritendinous PINP, whereas combined exercise and ERT enhanced muscle PINP after 72 h (interaction between loading and treatment P = 0.008). In neither skeletal muscle nor peritendinous fluid were IGF-I and IL-6 influenced by treatment or exercise. In conclusion, ERT was associated with enhanced synthesis of type I collagen in the skeletal muscle in response to acute exercise. In perspective, this indicates that the availability of estrogen in postmenopausal women is important for repair of muscle damage or remodeling of the connective tissue within the skeletal muscle after exercise.

IGF-I and TGF-β1 have distinct effects on phenotype and proliferation of intestinal fibroblasts

2002 ◽  
Vol 283 (3) ◽  
pp. G809-G818 ◽  
Author(s):  
James G. Simmons ◽  
Jolanta B. Pucilowska ◽  
Temitope O. Keku ◽  
P. Kay Lund
Keyword(s):  
Smooth Muscle ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Smooth Muscle Actin ◽  
Fiber Formation ◽  
Type I ◽  
Muscle Actin ◽  
Stress Fiber Formation ◽  
Igf I ◽  
Tgf Β1

Insulin-like growth factor I (IGF-I) and transforming growth factor-β1 (TGF-β1) are upregulated in myofibroblasts at sites of fibrosis in experimental enterocolitis and in Crohn's disease (CD). We compared the sites of expression of IGF-I and TGF-β1 in a rat peptidoglycan-polysaccharide (PG-PS) model of chronic granulomatous enterocolitis and fibrosis. We used the human colonic CCD-18Co fibroblast/myofibroblast cell line to test the hypothesis that TGF-β1 and IGF-I interact to regulate proliferation, collagen synthesis, and activated phenotype typified by expression of α-smooth muscle actin and organization into stress fibers. IGF-I potently stimulated while TGF-β1 inhibited basal DNA synthesis. TGF-β1 and IGF-I each had similar but not additive effects to induce type I collagen. TGF-β1 but not IGF-I potently stimulated expression of α-smooth muscle actin and stress fiber formation. IGF-I in combination with TGF-β1 attenuated stress fiber formation without reducing α-smooth muscle actin expression. Stress fibers were not a prerequisite for increased collagen synthesis. TGF-β1 upregulated IGF-I mRNA, which led us to examine the effects of IGF-I in cells previously activated by TGF-β1 pretreatment. IGF-I potently stimulated proliferation of TGF-β1-activated myofibroblasts without reversing activated fibrogenic phenotype. We conclude that TGF-β1 and IGF-I both stimulate type I collagen synthesis but have differential effects on activated phenotype and proliferation. We propose that during intestinal inflammation, regulation of activated phenotype and proliferation may require sequential actions of TGF-β1 and IGF-I, but they may act in concert to increase collagen deposition.

Role of TGF-β1 in relation to exercise-induced type I collagen synthesis in human tendinous tissue

2003 ◽  
Vol 95 (6) ◽  
pp. 2390-2397 ◽  
Author(s):  
Katja Heinemeier ◽  
Henning Langberg ◽  
Jens L. Olesen ◽  
Michael Kjaer
Keyword(s):  
Mechanical Loading ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Plasma Concentrations ◽  
Treadmill Running ◽  
Blood Levels ◽  
Type I ◽  
Response To Exercise

Mechanical loading of tissue is known to influence local collagen synthesis, and microdialysis studies indicate that mechanical loading of human tendon during exercise elevates tendinous type I collagen production. Transforming growth factor-β1 (TGF-β1), a potent stimulator of type I collagen synthesis, is released from cultured tendon fibroblasts in response to mechanical loading. Thus TGF-β1 could link mechanical loading and collagen synthesis in tendon tissue in vivo. Tissue levels of TGF-β1 and type I collagen metabolism markers [procollagen I COOH-terminal propeptide (PICP) and COOH-terminal telopeptide of type I collagen (ICTP)] were measured by microdialysis in peritendinous tissue of the Achilles' tendon in six male volunteers before and after treadmill running (1 h, 12 km/h, 3% uphill). In addition, blood levels of TGF-β1, PICP, and ICTP were obtained. PICP levels increased 68 h after exercise ( P < 0.05). Dialysate levels of TGF-β1 changed from 303 ± 46 pg/ml (at rest) to 423 ± 86 pg/ml 3 h postexercise. This change was nonsignificant, but the decay of tissue TGF-β1 after catheter insertion was markedly delayed by exercise compared with the decay seen in resting subjects. Plasma concentrations of TGF-β1 rose 30% in response to exercise ( P < 0.05 vs. pre). Our observations indicate an increased local production of type I collagen in human peritendinous tissue in response to uphill running. Although not conclusive, changes in circulating and local TGF-β1, in response to exercise, suggest a role for TGF-β1 in mechanical regulation of local collagen type I synthesis in tendon-related connective tissue in vivo.

Effect of administration of oral contraceptives in vivo on collagen synthesis in tendon and muscle connective tissue in young women

2009 ◽  
Vol 106 (4) ◽  
pp. 1435-1443 ◽  
Author(s):  
M. Hansen ◽  
B. F. Miller ◽  
L. Holm ◽  
S. Doessing ◽  
S. G. Petersen ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Patellar Tendon ◽  
Oral Contraceptives ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Vastus Lateralis ◽  
Type I ◽  
High Concentration ◽  
Igf I

Women are at greater risk than men for certain kinds of diseases and injuries, which may at least partly be caused by sex hormonal differences. We aimed to test the influence of estradiol in vivo on collagen synthesis in tendon, bone, and muscle. Two groups of young, healthy women similar in age, body composition, and exercise-training status were included. The two groups were either habitual users of oral contraceptives exposed to a high concentration of synthetic estradiol and progestogens (OC, n = 11), or non-OC-users tested in the follicular phase of the menstrual cycle characterized by low concentrations of estradiol and progesterone (control, n = 12). Subjects performed 1 h of one-legged kicking exercise. The next day collagen fractional synthesis rates (FSR) in tendon and muscle connective tissue were measured after a flooding dose of [13C]proline followed by biopsies from the patellar tendon and vastus lateralis in both legs. Simultaneously, microdialysis catheters were inserted in vastus lateralis and in front of the patellar tendon for measurement of insulin-like growth factor I (IGF-I) and its binding proteins. Serum NH2-terminal propeptide of type I collagen (PINP) and urine COOH-terminal telopeptides of type-I collagen (CTX-I) were measured as markers for bone synthesis and breakdown, respectively. Tendon FSR and PINP were lower in OC compared with control. An increase in muscle collagen FSR postexercise was only observed in control ( P < 0.05). Furthermore, the results indicate a lower bioavailability of IGF-I in OC. In conclusion, synthetic female sex hormones administered as OC had an inhibiting effect on collagen synthesis in tendon, bone, and muscle connective tissue, which may be related to a lower bioavailability of IGF-I.

scholarly journals STAT3 controls COL1A2 enhancer activation cooperatively with JunB, regulates type I collagen synthesis posttranscriptionally, and is essential for lung myofibroblast differentiation

2018 ◽  
Vol 29 (2) ◽  
pp. 84-95 ◽  
Author(s):  
Ioannis Papaioannou ◽  
Shiwen Xu ◽  
Christopher P. Denton ◽  
David J. Abraham ◽  
Markella Ponticos
Keyword(s):  
Protein Level ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Type I ◽  
Myofibroblast Differentiation ◽  
Matrix Remodeling ◽  
Collagen Production

STAT3 binds the collagen 1α2 enhancer and cooperates with JunB to activate it. We also show that fibroblasts have high basal levels of STAT3 activation, so activation of the enhancer by STAT3 is not affected by IL6. However, IL6 results in protein-level changes. Inhibition of STAT3 blocks collagen production and matrix remodeling.

scholarly journals Autophagy facilitates type I collagen synthesis in periodontal ligament cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomomi Nakamura ◽  
Motozo Yamashita ◽  
Kuniko Ikegami ◽  
Mio Suzuki ◽  
Manabu Yanagita ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Periodontal Diseases ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Physiological Role ◽  
Type I ◽  
Periodontal Tissue ◽  
Pdl Cells

AbstractAutophagy is a lysosomal protein degradation system in which the cell self-digests its intracellular protein components and organelles. Defects in autophagy contribute to the pathogenesis of age-related chronic diseases, such as myocardial infarction and rheumatoid arthritis, through defects in the extracellular matrix (ECM). However, little is known about autophagy in periodontal diseases characterised by the breakdown of periodontal tissue. Tooth-supportive periodontal ligament (PDL) tissue contains PDL cells that produce various ECM proteins such as collagen to maintain homeostasis in periodontal tissue. In this study, we aimed to clarify the physiological role of autophagy in periodontal tissue. We found that autophagy regulated type I collagen synthesis by elimination of misfolded proteins in human PDL (HPDL) cells. Inhibition of autophagy by E-64d and pepstatin A (PSA) or siATG5 treatment suppressed collagen production in HPDL cells at mRNA and protein levels. Immunoelectron microscopy revealed collagen fragments in autolysosomes. Accumulation of misfolded collagen in HPDL cells was confirmed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. E-64d and PSA treatment suppressed and rapamycin treatment accelerated the hard tissue-forming ability of HPDL cells. Our findings suggest that autophagy is a crucial regulatory process that facilitates type I collagen synthesis and partly regulates osteoblastic differentiation of PDL cells.

scholarly journals Endothelial cell growth factor and heparin regulate collagen gene expression in keloid fibroblasts

1991 ◽  
Vol 278 (3) ◽  
pp. 863-869 ◽  
Author(s):  
E M L Tan ◽  
J Peltonen
Keyword(s):  
Gene Expression ◽  
Endothelial Cell ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Collagen Type ◽  
Collagen Type I ◽  
Type I ◽  
Collagen Gene ◽  
Endothelial Cell Growth Factor ◽  
Endothelial Cell Growth

Keloids are benign cutaneous tumours characterized by excess deposition of collagen, specifically type I collagen. We report here that collagen biosynthesis, as measured by hydroxyproline synthesis, was markedly inhibited by 65-80% by the combination of endothelial cell growth factor (ECGF) supplement and heparin in keloid fibroblast cultures. Fibroblast cultures that were incubated with ECGF alone also demonstrated a measurable decrease of approx. 50% in collagen synthesis compared with control cultures. The inhibition of collagen synthesis was related to the down-regulation of collagen gene expression. Quantitative measurements of mRNA-cDNA hybrids revealed that the gene expression of collagen type I was decreased by more than 80% by heparin and ECGF. Markedly diminished levels of mRNA encoding collagen type I were also observed in cultures incubated with ECGF alone. The results show that ECGF and heparin elicit a negative regulatory effect on collagen production, and that this inhibition is due largely to the down-regulation of the pro-alpha 1(I) of type I collagen gene. Furthermore, ECGF has a potent suppressive effect, and heparin provides an additive effect to this inhibitory phenomenon.

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