Addition of Nitric Oxide Through Nitric Oxide-paracetamol Enhances Healing Rat Achilles Tendon

Murrell, George A. C.; Tang, Gong-yao; Appleyard, Richard; Soldato, Piero Del; Wang, Min Xia

doi:10.1007/s11999-008-0271-y

Cited by 20 publications

(17 citation statements)

References 22 publications

(30 reference statements)

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“…These genes are often coregulated to closely control the levels of NO (34). NO has been previously shown to be important during tendon healing by improving the organization of the collagen and regulating the inflammatory response (6,29,35,36,42,49,50).…”

Section: Discussionmentioning

confidence: 99%

Influence of a single loading episode on gene expression in healing rat Achilles tendons

Eliasson

Andersson

Aspenberg

2012

Journal of Applied Physiology

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Mechanical loading stimulates tendon healing via mechanisms that are largely unknown. Genes will be differently regulated in loaded healing tendons, compared with unloaded, just because of the fact that healing processes have been changed. To avoid such secondary effects and study the effect of loading per se, we therefore studied the gene expression response shortly after a single loading episode in otherwise unloaded healing tendons. The Achilles tendon was transected in 30 tail-suspended rats. The animals were let down from the suspension to load their tendons on a treadmill for 30 min once, 5 days after tendon transection. Gene expression was studied by Affymetrix microarray before and 3, 12, 24, and 48 h after loading. The strongest response in gene expression was seen 3 h after loading, when 150 genes were up- or downregulated (fold change ≥2, P ≤ 0.05). Twelve hours after loading, only three genes were upregulated, whereas 38 were downregulated. Fewer than seven genes were regulated after 24 and 48 h. Genes involved in the inflammatory response were strongly regulated at 3 and 12 h after loading; this included upregulation of iNOS, PGE synthase, and IL-1β. Also genes involved in wound healing/coagulation, angiogenesis, and production of reactive oxygen species were strongly regulated by loading. Microarray results were confirmed for 16 selected genes in a repeat experiment (N = 30 rats) using real-time PCR. It was also confirmed that a single loading episode on day 5 increased the strength of the healing tendon on day 12. In conclusion, the fact that there were hardly any regulated genes 24 h after loading suggests that optimal stimulation of healing requires a mechanical loading stimulus every day.

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Section: Discussionmentioning

confidence: 99%

Influence of a single loading episode on gene expression in healing rat Achilles tendons

Eliasson

Andersson

Aspenberg

2012

Journal of Applied Physiology

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“…Preliminary studies utilizing adalimumab (a tumor necrosis factor-alpha blocker), anakinra (an interleukin-1 antagonist) [ 146 ] or apronitin (a MMP-inhibitor) [ 147 ] or tropisetron (a 5-HT3 receptor antagonist with anti-inflammatory properties) have produced encouraging results [ 89 ]. Local NO delivery, by means of glycerol trinitrate patches, has been proven to be beneficial by some authors, with reduction of pain and increases in strength in subjects with tennis elbow, Achilles TP and supraspinatus tendinosis [ 148 ], but other studies have failed to support its efficacy in Achilles TP [ 149 , 150 ]. A variety of materials have also been used in the formation of scaffolds, including natural components, such as collagen [ 151 ], as well as copolymers [ 152 ].…”

Section: Therapeutic Perspectivesmentioning

confidence: 99%

Pathogenesis of tendinopathies: inflammation or degeneration?

et al. 2009

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The intrinsic pathogenetic mechanisms of tendinopathies are largely unknown and whether inflammation or degeneration has the prominent role is still a matter of debate. Assuming that there is a continuum from physiology to pathology, overuse may be considered as the initial disease factor; in this context, microruptures of tendon fibers occur and several molecules are expressed, some of which promote the healing process, while others, including inflammatory cytokines, act as disease mediators. Neural in-growth that accompanies the neovessels explains the occurrence of pain and triggers neurogenic-mediated inflammation. It is conceivable that inflammation and degeneration are not mutually exclusive, but work together in the pathogenesis of tendinopathies. IntroductionPrimary disorders of tendons are common and account for a high proportion of referrals to rheumatologists and orthopedic surgeons [1]. The most commonly involved tendons are the rotator cuff (particularly supraspinatus) and biceps brachii tendons in the shoulder, the forearm extensor and flexor tendons in the forearm, the patella tendon in the knee, the Achilles tendon in the lower leg, and the tibialis posterior tendon in the ankle and foot.Historically, the term tendinitis was used to describe chronic pain referring to a symptomatic tendon, thus implying inflammation as a central pathological process. However, traditional treatment modalities aimed at modulating inflammation have limited success [2] and histological studies of surgical specimens consistently show the presence of degenerative lesions, with either absent or minimal inflammation [3,4]. As will be clear in this review, we favor the hypothesis that inflammation and degenerative changes often coexist in the course of tendon disorders, and their relative contributions are difficult to dissect. Therefore, the definition of 'tendinitis' has been largely abandoned and the terms 'tendinosis' or, more generically, 'tendinopathy' (TP) are now currently preferred [5].In this review we summarize recent findings useful for understanding the pathogenesis of primary tendon diseases. First, suggestions coming from epidemiology, histopathology and clinics are reported, then we discuss new data on biochemical changes that occur in experimental and human TPs. Finally, we propose a unifying theory, drawn from both experimental and clinical data. Anatomy and physiologyThe tendons are made up of bundles of collagen fibrils (primary, secondary and tertiary fibers), each wrapped in endotenon, which in turn is enveloped by an epitenon, forming the actual tendon. A true synovial sheath is present only in some tendons, such as tibialis posterior, peroneal, and extensor and flexor tendons of the wrist and the hand; other

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“…Yuan et al found that daily and localized injection of NO-generating nitroflurbiprofen improved collagen organization and tendon stress in rats with injured Achilles tendons 10 d post-injury relative to controls [159]. Similarly, the effect of injecting nitroparacetamol (48 mg kg −1 per day) at wounded Achilles tendons in rats had no significant effect on the failure load of the tendons, but the treatment increased both collagen organization and content [160]. …”

Section: Nitric Oxide In Tendon Healingmentioning

confidence: 99%

Local delivery of nitric oxide: Targeted delivery of therapeutics to bone and connective tissues

Nichols

Storm

Koh

et al. 2012

Advanced Drug Delivery Reviews

117

105

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Non-invasive treatment of injuries and disorders affecting bones and connective tissue is a significant challenge facing the medical community. A treatment route that has recently been proposed is nitric oxide (NO) therapy. Nitric oxide plays several roles in physiology with many conditions lacking adequate levels of NO. As NO is a radical, localized delivery via NO donors is essential to promoting biological activity. Herein, we review current literature related to therapeutic NO delivery in the treatment of bone, skin and tendon repair.

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Addition of Nitric Oxide Through Nitric Oxide-paracetamol Enhances Healing Rat Achilles Tendon

Cited by 20 publications

References 22 publications

Influence of a single loading episode on gene expression in healing rat Achilles tendons

Influence of a single loading episode on gene expression in healing rat Achilles tendons

Pathogenesis of tendinopathies: inflammation or degeneration?

Local delivery of nitric oxide: Targeted delivery of therapeutics to bone and connective tissues

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