Sequential extracts of human bone show differing collagen synthetic rates

2002 ◽  
Vol 30 (2) ◽  
pp. 61-65 ◽  
Author(s):  
J. Babraj ◽  
D.J. Cuthbertson ◽  
P. Rickhuss ◽  
W. Meier-Augenstein ◽  
K. Smith ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Human Bone ◽  
Bone Collagen ◽  
Type I ◽  
Human Beings ◽  
Collagen Turnover ◽  
Bone Collagen Synthesis

Type I collagen is the major bone protein. Little is known quantitatively about human bone collagen synthesis in vivo, despite its importance for the understanding of bone formation and turnover. Our aim was to develop a method that could be used for the physiological and pathophysiological investigation of human bone collagen synthesis. We have carried out preliminary studies in patients undergoing hip replacement and in pigs to validate the use of the flooding dose method using 13C- or 15N-labelled proline and we have now refined our techniques to allow them to be used in a normal clinical or physiological setting. The results show that the application of a flooding dose causes bone free-proline labelling to equilibrate with that of blood in pigs and human beings, so that only 150 mg of bone will provide enough sample to prepare and measure the labelling of three fractions of bone collagen (dissolved in NaCl, acetic acid and pepsin/acetic acid) which have the same relative labelling (1.0:0.43:0.1) as measured by GC-combustion-isotope ratio MS. The rates of incorporation were substantially faster than in skeletal muscle samples taken at the same time. The results suggest that different fractions of human bone collagen turnover at markedly higher rates than had been previously considered. This approach should allow us to discover how growth and development, food, activity and drugs affect bone collagen turnover and to measure the effects on it of ageing and bone disease.

Melatonin stimulates proliferation and type I collagen synthesis in human bone cells in vitro

1999 ◽  
Vol 27 (2) ◽  
pp. 106-110 ◽  
Author(s):  
Osamu Nakade ◽  
Hiroki Koyama ◽  
Hirohiko Ariji ◽  
Akihiro Yajima ◽  
Tohru Kaku
Keyword(s):  
Collagen Synthesis ◽  
Type I Collagen ◽  
Bone Cells ◽  
Human Bone ◽  
Type I

Interleukin-6: a growth factor stimulating collagen synthesis in human tendon

2011 ◽  
Vol 110 (6) ◽  
pp. 1549-1554 ◽  
Author(s):  
Mette Bisgaard Andersen ◽  
Jessica Pingel ◽  
Michael Kjær ◽  
Henning Langberg
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Achilles Tendon ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Type I ◽  
Collagen Turnover ◽  
Potential Growth ◽  
Human Tendon ◽  
Turnover Markers

Human connective tissue, e.g., tendon, responds dynamically to physical activity, with collagen synthesis being increased after both acute and prolonged exercise or training. Markers of collagen synthesis and degradation as well as concentration of several potential growth factors have been shown to increase markedly in the peritendinous tissue around the human Achilles tendon following exercise. Of these potential growth factors interleukin-6 (IL-6) showed the largest fold increase, suggesting that IL-6 may be involved in transforming mechanical loading into collagen synthesis in human tendon tissue. In the present study the tissue levels of type I collagen turnover markers [procollagen type I NH2-terminal propeptide (PINP) and C-OOH terminal telopeptide of type I collagen (ICTP)] were measured by the use of microdialysis in peritendinous tissue of the Achilles tendon in 14 male volunteers, who had recombinant human IL-6 (rhIL-6) infused into the peritendinous tissue of the Achilles' tendon in one leg, with the other leg serving as control. Subjects were randomly assigned to either a resting group or an exercise group performing a 1-h treadmill run (12 km/h, 2% uphill) before infusion. In addition to IL-6, serum concentrations of collagen turnover markers PINP, ICTP, and COOH-terminal telopeptide of type I collagen (ICTX) were measured. The peritendinous concentration of PINP rose markedly in response to rhIL-6 infusion in both the exercise and the rest group, demonstrating that infusion of IL-6 significantly stimulates collagen synthesis in the peritendinous tissue in humans. Exercise alone did not result in an increased collagen synthesis. This indicates that IL-6 is involved in the collagen synthesis and supports the hypothesis that IL-6 is an important growth factor of the connective tissue in healthy human tendons.

scholarly journals Human Stem Cell Derived Osteocytes in Bone-on-Chip

MRS Advances ◽  
2018 ◽  
Vol 3 (26) ◽  
pp. 1443-1455
Author(s):  
E. Budyn ◽  
N. Gaci ◽  
S. Sanders ◽  
M. Bensidhoum ◽  
E. Schmidt ◽  
...  
Keyword(s):  
Stem Cell ◽  
Type I Collagen ◽  
Mechanical Load ◽  
Human Bone ◽  
Type I ◽  
Native Bone ◽  
On Chip

ABSTRACTHuman mesenchymal stem cells were reseeded in decellularized human bone subject to a controlled mechanical loading to create a bone-on-chip that was cultured for over 26 months. The cell morphology and their secretome were characterized using immunohistochemistry and in situ immunofluorescence under confocal microscopy. The presence of stem cell derived osteocytes was confirmed at 547 days. Different cell populations were identified. Some cells were connected by long processes and formed a network. Comparison of the MSCs in vitro reorganization and calcium response to in situ mechanical stimulation were compared to MLOY4 cells reseeded on human bone. The bone-on-chip produced an ECM of which the strength was nearly a quarter of native bone after 109 days and that contained calcium minerals at 39 days and type I collagen at 256 days. The cytoplasmic calcium concentration variations seemed to adapt to the expected in vivo mechanical load at the successive stages of cell differentiation in agreement with studies using fluid shear flow stimulation. Some degree of bone-like formation over a long period of time with the formation of a newly formed matrix was observed.

scholarly journals Ageing and human bone collagen synthesis

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
John Babraj ◽  
Daniel Cuthbertson ◽  
Kenneth Smith ◽  
Peter Rickhus ◽  
Michael Rennie
Keyword(s):  
Collagen Synthesis ◽  
Human Bone ◽  
Bone Collagen ◽  
Bone Collagen Synthesis

Effects of long-term immobilization and recovery on human triceps surae and collagen turnover in the Achilles tendon in patients with healing ankle fracture

2008 ◽  
Vol 105 (2) ◽  
pp. 420-426 ◽  
Author(s):  
Britt Christensen ◽  
Eva Dyrberg ◽  
Per Aagaard ◽  
Susanne Enehjelm ◽  
Michael Krogsgaard ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Achilles Tendon ◽  
Ankle Fracture ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Calf Muscle ◽  
Triceps Surae ◽  
Type I ◽  
Collagen Turnover ◽  
Synthesis And Degradation

The aim of the present study was to analyze how human tendon connective tissue responds to an ∼7-wk period of immobilization and a remobilization period of a similar length, in patients with unilateral ankle fracture, which is currently unknown. Calf muscle cross-sectional area (CSA) decreased by 15% (5,316 to 4,517 mm2) and strength by 54% (239 to 110 N·m) in the immobilized leg after 7 wk. During the 7-wk remobilization, the CSA increased by 9% (to 4,943 mm2) and strength by 37% (to 176 Nm). Achilles tendon CSA did not change significantly during either immobilization or remobilization. Local collagen turnover was measured as the peritendinous concentrations of NH2-terminal propeptide of type I collagen (PINP) and COOH-terminal telopeptide region of type I collagen (ICTP), markers thought to be indexes of type I collagen synthesis and degradation, respectively. Both markers were increased (PINP: 257 vs. 56 ng/ml; ICTP: 9.8 vs. 2.1 μg/l) in the immobilized leg compared with the control leg after the 7 wk of immobilization, and levels decreased again in the immobilized leg during the recovery period (PINP: 103 vs. 44 ng/ml; ICTP: 4.2 vs. 1.9 μg/l). A significant reduction in calf muscle CSA and strength was found in relation to 7 wk of immobilization. Immobilization increased both collagen synthesis and degradation in tendon near tissue. However, it cannot be excluded that the facture of the ankle in close proximity could have affected these data. Remobilization increased muscle size and strength and tendon synthesis and degradation decreased to baseline levels. These dynamic changes in tendon connective tissue turnover were not associated with macroscopic changes in tendon size.

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.

Dexamethasone suppresses in vivo levels of bone collagen synthesis in neonatal mice

Bone ◽  
1997 ◽  
Vol 20 (1) ◽  
pp. 41-46 ◽  
Author(s):  
S. Advani ◽  
D. LaFrancis ◽  
E. Bogdanovic ◽  
P. Taxel ◽  
L.G. Raisz ◽  
...  
Keyword(s):  
Collagen Synthesis ◽  
Bone Collagen ◽  
Neonatal Mice ◽  
Bone Collagen Synthesis

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.

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