Modulation of tendon healing by nitric oxide

Murrell, George A. C.; Szabó, Csaba; Hannafin, Jo A.; Jang, Daniel; Dolan, Martin M.; Deng, Xiang‐Hua; Murrell, Dédée F.; Warren, Robert F.

doi:10.1007/s000110050027

Cited by 145 publications

(140 citation statements)

References 16 publications

(19 reference statements)

Supporting

Mentioning

116

Contrasting

Unclassified

Order By: Relevance

“…11,12 Our previous reports also confirmed that NOS is upregulated during tendon healing and inhibition of NOS resulted in a significant reduction in cross-section area and failure load of healing Achilles tendon constructs. [13][14][15] We have also noted in our recent clinical trials, that application of topical nitric oxide improved early pain with activity, late functional measures, and outcomes of patients with extensor tendinosis, tendinosis of the extensor mechanism in the elbow, the Achilles and the supraspinatus in the shoulder. [16][17][18] Most of the findings, however, are from the studies on cutaneous wound healing.…”

Section: Introductionmentioning

confidence: 78%

Nitric oxide enhances collagen synthesis in cultured human tendon cells

Xia

Szomor

Wang

et al. 2005

Journal Orthopaedic Research

View full text Add to dashboard Cite

Collagen deposition is an important process that occurs during wound healing. We and others have shown that nitric oxide (NO) is important in tendon healing. The mechanisms whereby healing is enhanced are, however, undetermined. The aim of this study was to investigate whether NO could enhance collagen synthesis in cultured human tendon cells via exogenous NO and via an adenovirus containing the gene for inducible nitric oxide synthase (Ad-iNOS). Tendon cells from the torn edge of the tendons of patients undergoing rotator cuff repair surgery were cultured following collagenase digestion, and stimulated with exogenous NO (SNAP), transfected with Ad-iNOS, and treated with the NOS inhibitor, L-NMMA. Total protein and collagen synthesis were evaluated by 3 H-proline and collagenase sensitive 3 H-proline incorporation in human tendon cells. High doses of exogenous NO (SNAP) inhibited collagen synthesis. Lower doses enhanced total protein and collagen synthesis of the tendon cells. Ad-iNOS successfully transfected active iNOS into human tendon cells in vitro and also enhanced total protein and collagen synthesis of the tendon cells. The NOS inhibitor, L-NMMA, inhibited the effects of iNOS on the cells. Our studies show for first time that nitric oxide can enhance collagen synthesis in human tendon cells in vitro. These results may explain, in part, at least, the beneficial effects of NO donors in animal models and during the treatment of tendonopathies in human clinical trials. ß

show abstract

Section: Introductionmentioning

confidence: 78%

Nitric oxide enhances collagen synthesis in cultured human tendon cells

Xia

Szomor

Wang

et al. 2005

Journal Orthopaedic Research

View full text Add to dashboard Cite

show abstract

“…48 The expression of growth factors and other potential modulators of tendon cell activity has been shown to increase in tendino pathy, including transforming growth factor β, platelet-derived growth factor receptor and neuro transmitters, such as glutamate and substance P. 42,47,[49][50][51] These changes might, however, be part of the healing response of the tissue and a requisite for tendon repair. 52,53 …”

Section: Molecular Pathology Of Tendinopathymentioning

confidence: 99%

Tendinopathy—from basic science to treatment

2008

View full text Add to dashboard Cite

“…5 We have shown that NO and the NOSs are important for the normal healing of rat Achilles tendon. 6 Transected Achilles tendons in rats in which NOS activity was inhibited [by means of oral administration of the NOS inhibitor N omeganitro-L-arginine methyl ester (L-NAME)] resulted in a significant reduction in cross-sectional area [30% at day 7 ( p < 0.01), and 50% at day 15 ( p < 0.001)] and failure load (24% at day 7, p < 0.01) of the healing tendon compared to untreated tendons. Rats fed L-NAMEs inactive enantiomer D-NAME healed normally.…”

Section: Introductionmentioning

confidence: 99%

Gene expression changes in SNAP-stimulated and iNOS-transfected tenocytes—expression of extracellular matrix genes and its implications for tendon-healing

Molloy¹,

Bock²,

Wang³

et al. 2006

J. Orthop. Res.

View full text Add to dashboard Cite

Nitric oxide (NO) has a variety of physiological roles, including acting as a key mediator in various phases of tendon healing, but its importance as a modulator of gene expression during tendon healing has not been well studied. The current study used microarray analysis to elucidate global gene expression after transfection with inducible nitric oxide synthase (iNOS) in tenocytes isolated from the injured rotator cuff tendons of human patients. We show that the expression of a wide range of genes is affected by NO, with many activated genes having known roles in healing. Of particular significance is that NOS overexpression stimulates the transcription and translation of a range of extracellular matrix genes important to the structure of connective tissues such as tendons, including collagen Ia1, collagen IIIa1, collagen IVa5, biglycan, decorin, laminin, and matrix metalloproteinase 10 (MMP10). These genes were also shown to respond to stimulation by the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) in a dose-dependant manner. We further show that varying levels of NO significantly affect cellular adhesion in tenocytes, a critical process during tendon repair. These findings will be of use when optimizing the dose of NO delivery in further work investigating NO as potential treatment of tendon injuries. ß

show abstract

Modulation of tendon healing by nitric oxide

Cited by 145 publications

References 16 publications

Nitric oxide enhances collagen synthesis in cultured human tendon cells

Nitric oxide enhances collagen synthesis in cultured human tendon cells

Tendinopathy—from basic science to treatment

Gene expression changes in SNAP-stimulated and iNOS-transfected tenocytes—expression of extracellular matrix genes and its implications for tendon-healing

Contact Info

Product

Resources

About