Adaptation of bone and tendon to prolonged hindlimb suspension in rats

Vailas, A. C.; DeLuna, D.; Lewis, L.; Curwin, Sandra; Roy, Roland R.; Alford, Elward K.

doi:10.1152/jappl.1988.65.1.373

Cited by 54 publications

(30 citation statements)

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“…Our values for hydroxyproline content in control rats are in agreement with previous results published for tendons and other similar connective tissues (Takacs and Verzar, 1968;Vailas et al, 1985Vailas et al, , 1988. Although long term monitoring for hydroxyproline content during tendon degeneration and regeneration has never been clearly reported, we showed that the rapid loss of hydroxyproline coincides with the accumulation of PMNs and Ms, which supports the hypothesis that leukocytes phagocytose and digest collagen during the inflammatory phase.…”

Section: Effects Of Diclofenac On Tendon Inflammation and Regenerationsupporting

confidence: 92%

Nonsteroidal Anti-Inflammatory Drug Reduces Neutrophil and Macrophage Accumulation but Does Not Improve Tendon Regeneration

Marsolais

Côté

Frenette

2003

Laboratory Investigation

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SUMMARY:Whether nonsteroidal anti-inflammatory drugs have a beneficial effect on tendon regeneration is still a matter of debate. Given that inflammatory cells are thought to induce nonspecific damage following an injury, we tested the hypothesis that a 3-day treatment with diclofenac would protect tendons from inflammatory cell injury and would promote healing. Neutrophil and ED1 ϩ macrophage concentrations were determined in the paratenon and the core of the rat Achilles tendon following collagenase-induced injury. Hydroxyproline content, edema, and mechanical properties were also evaluated at 1, 3, 7, 14, and 28 days post-trauma. Collagenase injections induced a 70% decrease in the ultimate rupture point at Day 3. Diclofenac treatments (1 mg/kg bid) selectively decreased the accumulation of neutrophils and ED1 ϩ macrophages by 59% and 35%, respectively, in the paratenon, where blood vessels are numerous, but did not reduce the accumulation of neutrophils and ED1 ϩ macrophages in the core of the tendon. Edema was significantly reduced on Day 3 but persisted during the remodeling phase in the diclofenac-treated group only. The inhibition of leukocyte accumulation by diclofenac did not translate into a reduction of tissue damage or a promotion of tissue healing, because the mechanical properties of injured Achilles tendons were identical in placebo and diclofenac-treated groups. These results indicate that diclofenac reduced both edema and the accumulation of inflammatory cells within the paratenon but provided no biochemical or functional benefits for the Achilles tendon. (Lab Invest 2003, 83:991-999).

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Section: Effects Of Diclofenac On Tendon Inflammation and Regenerationsupporting

confidence: 92%

Nonsteroidal Anti-Inflammatory Drug Reduces Neutrophil and Macrophage Accumulation but Does Not Improve Tendon Regeneration

Marsolais

Côté

Frenette

2003

Laboratory Investigation

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“…The estimation of the ligament cell density was achieved by determining the amount of DNA using a modified method of Bonting and Jones (5) and as previously performed by our laboratory (9,38). A stock solution of 0.1 mg NaDNA (type I; Sigma-Aldrich) per 1 ml distilled H 2O was prepared and used as a standard.…”

Section: Biochemistrymentioning

confidence: 99%

Temporal extracellular matrix adaptations in ligament during wound healing and hindlimb unloading

Martinez¹,

Vailas²,

Vanderby³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Martinez DA, Vailas AC, Vanderby R Jr, Grindeland RE. Temporal extracellular matrix adaptations in ligament during wound healing and hindlimb unloading. Am J Physiol Regul Integr Comp Physiol 293: R1552-R1560, 2007. First published August 15, 2007 doi:10.1152/ajpregu.00423.2007.-Previous data from spaceflight studies indicate that injured muscle and bone heal slowly and abnormally compared with ground controls, strongly suggesting that ligaments or tendons may not repair optimally as well. Thus the objective of this study was to investigate the biochemical and molecular gene expression of the collagen extracellular matrix in response to medial collateral ligament (MCL) injury repair in hindlimb unloaded (HLU) rodents. Male rats were assigned to 3-and 7-wk treatment groups with three subgroups each: sham control, ambulatory healing (Amb-healing), and HLU-healing groups. Amb-and HLU-healing animals underwent bilateral surgical transection of their MCLs, whereas control animals were subjected to sham surgeries. All surgeries were performed under isoflurane anesthesia. After 3 wk or 7 wk of HLU, rats were euthanized and MCLs were surgically isolated and prepared for molecular or biochemical analyses. Hydroxyproline concentration and hydroxylysylpyridinoline collagen cross-link contents were measured by HPLC and showed a substantial decrement in surgical groups. MCL tissue cellularity, quantified by DNA content, remained significantly elevated in all HLU-healing groups vs. Amb-healing groups. MCL gene expression of collagen type I, collagen type III, collagen type V, fibronectin, decorin, biglycan, lysyl oxidase, matrix metalloproteinase-2, and tissue inhibitor of matrix metalloproteinase-1, measured by real-time quantitative PCR, demonstrated differential expression in the HLU-healing groups compared with Ambhealing groups at both the 3-and 7-wk time points. Together, these data suggest that HLU affects dense fibrous connective tissue wound healing and confirms previous morphological and biomechanical data that HLU inhibits the ligament repair processes.

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“…1 In developing countries where more individuals are involved in life-long physical labor and regular exercise, sinew ruptures remain relatively uncommon. With inactivity, sinews lose collagen, 2,3 and become brittle and stiff, 4 making them prone to injury. In contrast, exercise increases the rate of collagen turnover, 5 indicating that mechanical loading is of primary importance in the maintenance of sinew function.…”

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confidence: 99%

Optimizing an Intermittent Stretch Paradigm Using ERK1/2 Phosphorylation Results in Increased Collagen Synthesis in Engineered Ligaments

Paxton

Hagerty

Andrick

et al. 2012

Tissue Engineering Part A

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Dynamic mechanical input is believed to play a critical role in the development of functional musculoskeletal tissues. To study this phenomenon, cyclic uniaxial mechanical stretch was applied to engineered ligaments using a custom-built bioreactor and the effects of different stretch frequency, amplitude, and duration were determined. Stretch acutely increased the phosphorylation of p38 (3.5 -0.74-fold), S6K1 (3.9 -0.19-fold), and ERK1/2 (2.45 -0.32-fold). The phosphorylation of ERK1/2 was dependent on time, rather than on frequency or amplitude, within these constructs. ERK1/2 phosphorylation was similar following stretch at frequencies from 0.1 to 1 Hz and amplitudes from 2.5% to 15%, whereas phosphorylation reached maximal levels at 10 min of stretch and returned toward basal within 60 min of stretch. Following a single 10-min bout of cyclic stretch, the cells remained refractory to a second stretch for up to 6 h. Using the phosphorylation of ERK1/2 as a guide, the optimum stretch paradigm was hypothesized to be 10 min of stretch at 2.5% of resting length repeated every 6 h. Consistent with this hypothesis, 7 days of stretch using this optimized intermittent stretch program increased the collagen content of the grafts more than a continuous stretch program (CTL = 3.1% -0.44%; CONT = 4.8% -0.30%; and INT = 5.9% -0.56%). These results suggest that short infrequent bouts of loading are optimal for improving engineered tendon and ligament physiology.

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Adaptation of bone and tendon to prolonged hindlimb suspension in rats

Cited by 54 publications

References 0 publications

Nonsteroidal Anti-Inflammatory Drug Reduces Neutrophil and Macrophage Accumulation but Does Not Improve Tendon Regeneration

Nonsteroidal Anti-Inflammatory Drug Reduces Neutrophil and Macrophage Accumulation but Does Not Improve Tendon Regeneration

Temporal extracellular matrix adaptations in ligament during wound healing and hindlimb unloading

Optimizing an Intermittent Stretch Paradigm Using ERK1/2 Phosphorylation Results in Increased Collagen Synthesis in Engineered Ligaments

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