A collagenase gel/physical defect model for controlled induction of superficial digital flexor tendonitis

Watts, Ashlee E.; Nixon, Alan J.; Yeager, Amy E.; Mohammed, Hussni O.

doi:10.1111/j.2042-3306.2011.00471.x

Cited by 30 publications

(52 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Objectives: To assess the role of miR-29a in mediating col3 expression in an equine model of tendinopathy [2].…”

Section: Resultsmentioning

confidence: 99%

“…This mechanistic insight suggests that re-introduction of miR-29a may be a viable therapeutic option. Harper Adams University, Newport, Shropshire TF10 8NB; 2 School of Veterinary Science, University of Liverpool, Chester High Road, Neston, CH64 7TE, UK. Email: hmorrell@harper-adams.co.uk Reasons for performing study: Equine tendon injury is a major loss to the industry, consequently there is a growing body of published research seeking to improve tendon healing processes and outcomes.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Oral Sugar Test Responses with or Without Prior Fasting Helps Differentiate Previously Laminitic from Nonlaminitic Ponies

2016

Equine Veterinary Journal

View full text Add to dashboard Cite

Reasons for performing study: An oral sugar test (OST) is recommended for assessment of insulin dysregulation (ID) and is practically more convenient than the oral glucose test. OST results have not been specifically associated with a history of previous laminitis. Fasting prior to testing is advised but is impractical for solely pasture kept ponies.Objectives: To determine whether the OST can distinguish between ponies with a history of recurrent pasture-associated laminitis (PL) and nonlaminitic ponies (NL) when performed with or without prior fasting.Study design: Method evaluation study.Methods: Subjects: Adult native British ponies at spring pasture (PL n = 6, NL n = 4). Procedures: In each pony an OST was performed on 4 occasions, twice with and twice without prior fasting. Serum [insulin] was measured by radioimmunoassay. Differences in serum [insulin] response between NL and PL were assessed using mixed-effects models. An alternative cut-off and sampling times were extrapolated for use without fasting. >51 liu/ml at 30 or 60 min as a cutoff without fasting, 9/12 OSTs from PLs were positive, 7/8 OSTs from NLs were negative. First and second test results agreed in 9/10 ponies with fasting and 8/10 without fasting. Results Conclusions:The insulin response to the OST, at pasture in spring, is greater in most PL compared with NL ponies whether the test is performed with or without prior fasting. Methods: Thoroughbred horses (n = 8), ranging in age from 3 to 7 years, without clinical or ultrasonographic evidence of tendon injury were used. Collagenase-induced lesions were created in the tensile region of the superficial digital flexor tendon (SDFT) of one randomly selected forelimb using collagenase type I. To establish tendon explant cultures, the SDFT was aseptically excised from the midmetacarpal region of both forelimbs of 3 horses (aged 2-5 years). The impact of miR-29a was measured using quantitative-PCR, luciferase and Luminex cytokine multiplexes assays.Results: Col3 transcript levels were elevated at all time points of the 16-week trial peaking at Week 3, when col3 levels were 80-fold increased compared with uninjured controls. In contrast, miR-29a expression was significantly (P<0.01) downregulated throughout all time points. Col3 luciferase assay confirmed that miR-29a directly targets the 3' untranslated regions of col3. Furthermore, introduction of synthetic miR-29a into cultured equine tenocytes reduced col3 expression. Additionally, miR-29a inhibition resulted in a significant increase in col3 expression indicating that miR-29a is not only actively regulating col3 but its loss is an important factor in the increase of col3 production observed in tendinopathy.Conclusions: This work shows that injury-induced loss of miR-29a is responsible for the over-expression of col3 seen in tendinopathy. This mechanistic insight suggests that re-introduction of miR-29a may be a viable therapeutic option. School of Veterinary Science, University of Liverpool, Chester High Road, Neston, CH64 7TE, UK. Email...

show abstract

“…Objectives: To assess the role of miR-29a in mediating col3 expression in an equine model of tendinopathy [2].…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Oral Sugar Test Responses with or Without Prior Fasting Helps Differentiate Previously Laminitic from Nonlaminitic Ponies

2016

Equine Veterinary Journal

View full text Add to dashboard Cite

show abstract

“…Considering that the tissue specimens of injured tendons are not available for histopathological examination in clinical practice, the ultrasound and magnetic resonance imaging are the gold standard in diagnosing tendon disorders, with ultrasonography being cost-effective, non-invasive and generally accessible [10,11,21]. Several animal models are currently used in tendinopathy research including laboratory animals, like rabbits [5,23,25,26,29,33], rats [9,15,17] and mice [8] as well as companion animals, like horses [2,3,31] and dogs [20]. Despite the fact that veterinary patients are increasingly recognised as translational models of human tendinopathies [19,30] their use in experimental protocols seems controversial and is not accepted in several countries due to ethical issues.…”

Section: Introductionmentioning

confidence: 99%

Rabbit common calcanean tendon as an animal model: ultrasonographic anatomy and morphometry

Skalec

Janeczek²,

Janus³

et al. 2016

Folia Morphol

View full text Add to dashboard Cite

“…The relevance of collagenase-induced pathology to a condition involving mechanical overuse has been controversial in recent years because the former is a melting lesion that is difficult to standardize and erodes outwards with a marked inflammatory reaction including the paratendon (neither of which is a feature of natural lesions) (Schramme et al 2010;Watts et al 2012). It is also not known how prominent a role enzymatic activity plays at and after the occurrence of tendon rupture.…”

Section: Should We Use Experimental Horses?mentioning

confidence: 99%

“…It is also not known how prominent a role enzymatic activity plays at and after the occurrence of tendon rupture. More recently, mild to moderate-severity SDFT core lesions have been created using arthroscopic burrs or blades, with one involving insertion of collagenase gel into a needlecreated defect; some were microscopically and biochemically comparable with spontaneous injury (including MMP upregulation and formation of small-diameter collagen fibrils) with similarly protracted healing (Cadby et al 2013;Caniglia et al 2012;Schramme et al 2010;Watts et al 2012). Although these models might be of use to study postdisruption healing (and controlled therapeutic interventions by injuring tendons bilaterally) (Bosch et al 2011), the acute induction of injury cannot recapitulate the predisposing (exerciseinduced) microdamage that occurs in the natural situation ( potentially for weeks or even years before rupture).…”

Section: Should We Use Experimental Horses?mentioning

confidence: 99%

Achilles Tendon Injuries in Elite Athletes: Lessons in Pathophysiology from Their Equine Counterparts

Patterson-Kane¹,

Rich²

2014

ILAR Journal

View full text Add to dashboard Cite

Superficial digital flexor tendon (SDFT) injury in equine athletes is one of the most well-accepted, scientifically supported companion animal models of human disease (i.e., exerciseinduced Achilles tendon [AT] injury). The SDFT and AT are functionally and clinically equivalent (and important) energy-storing structures for which no equally appropriate rodent, rabbit, or other analogues exist. Access to equine tissues has facilitated significant advances in knowledge of tendon maturation and aging, determination of specific exercise effects (including early life), and definition of some of the earliest stages of subclinical pathology. Access to human surgical biopsies has provided complementary information on more advanced phases of disease. Importantly, equine SDFT injuries are only a model for acute ruptures in athletes, not the entire spectrum of human tendonopathy (including chronic tendon pain). In both, pathology begins with a potentially prolonged phase of accumulation of (subclinical) microdamage. Recent work has revealed remarkably similar genetic risk factors, including further evidence that tenocyte dysfunction plays an active role. Mice are convenient but not necessarily accurate models for multiple diseases, particularly at the cellular level. Mechanistic studies, including tendon cell responses to combinations of exercise-associated stresses, require a more thorough investigation of cross-species conservation of key stress pathway auditors. Molecular evidence has provided some context for the poor performance of mouse models; equines may provide better systems at this level. The use of horses may be additionally justifiable based on comparable species longevity, lifestyle factors, and selection pressure by similar infectious agents (e.g., herpesviruses) on general cell stress pathway evolution.

show abstract

A collagenase gel/physical defect model for controlled induction of superficial digital flexor tendonitis

Abstract: This model will allow for objective assessment of therapies for tendon regeneration in the mid-metacarpal SDFT prior to clinical trials and routine clinical application.

Cited by 30 publications

References 82 publications

Oral Sugar Test Responses with or Without Prior Fasting Helps Differentiate Previously Laminitic from Nonlaminitic Ponies

Oral Sugar Test Responses with or Without Prior Fasting Helps Differentiate Previously Laminitic from Nonlaminitic Ponies

Rabbit common calcanean tendon as an animal model: ultrasonographic anatomy and morphometry

Achilles Tendon Injuries in Elite Athletes: Lessons in Pathophysiology from Their Equine Counterparts

Contact Info

Product

Resources

About