Flexor tendon healing in the rat: a histologic and gene expression study

Oshiro, Wataru; Lou, Jueren; Xing, Xiaoyun; Tu, Yizheng; Manske, Paul R.

doi:10.1016/s0363-5023(03)00366-6

Cited by 150 publications

(171 citation statements)

References 16 publications

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“…In a normal tendon, restricted MMP-13 expression was observed in some fibroblastic cells and vascular component in the endotenon, suggesting the participation of MMP-13 in maintenance of homeostasis in matrix turnover in a tendon. Moreover, MMP-13 has been shown to be highly expressed in fibroblastic tissue in tendonitis in the horse (29) and to participate in collagen degradation during healing of the SDFT in the rat (32). These findings suggest cytes derived from the MTJ site and was increased most in both control and TNFα-treated tendinocytes from the OTJ site.…”

Section: Activity Of Prommps In Vitromentioning

confidence: 82%

Comparative study of the properties of tendinocytes derived from three different sites in the equine superficial digital flexor tendon

et al. 2010

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This aim of this study was to determine the characteristic differences in tendinocytes derived from three sites of the equine superficial digital flexor tendon (SDFT)-proximally the myotendinous junction (MTJ), mid-metacarpal (mM) and osteotendinous junction (OTJ)-in morphology, proliferation, and ability for synthesis of collagen and matrix metalloproteinases (MMPs). Little difference was observed in cell proliferation. Addition of tumor necrosis factor (TNF) α to the culture medium resulted in increased collagen synthesis by tendinocytes from all three sites. The amount of collagen synthesized by tendinocytes derived from the mM and OTJ was much larger than that synthesized by untreated tendinocytes. A collagen zymogram revealed that proMMP-13 synthesis was increased towards the distal site. However, TNFα treatment resulted in a significant decrease in the amount of proMMP-13 synthesized by tendinocytes from all three sites. On the other hand, a gelatin zymogram showed that the synthesis level of proMMP-9 tended to decrease towards the distal site, but there was little difference between synthesis levels of proMMP-9 before and after TNFα treatment. These results indicated that tendinocytes in the same tendon have different characteristics and that these characterisities would reflect the function of tendinocytes in vivo. Also, the isolated tendinocytes provided much information on the characteristics and properties of tendons for the ECM turnover system and on the responsiveness of tendinocytes to complex inflammatory responses in a tendinopathy condition.Tendon injury, especially in the superficial digital flexor tendon (SDFT), has proved to be a major problem for racehorses. Recent studies have shown that about 10-30% of racehorses suffer from tendonitis (8, 30). Interestingly, tendonitis occurs more frequently in the forelimb, especially in the SDFT rather than the deep digital flexor tendon (DDFT), and rarely occurs in the common digital extensor tendon (CDET) (1, 30). The vulnerability of the SDFT is related to its functions in weight supporting and in accumulation and transmission of elastic force for effective movement. Damage to the SDFT usually occurs during high-speed work or racing competition in which the forelimbs are pulled up to the highest position to bear maximum load or straining power (14,35). Moreover, tendonitis in the SDFT occurs in the mid-metacarpal (mM) site in most cases (1). Therefore, structural properties of the tendons might reflect the occurrence ratio of tendonitis (10). The etiology of tendonitis has been discussed in many reports; however, there is little information regarding the mechanism of tendon degradation. Extracellular matrix (ECM) turnover in a tendon might occur repeatedly and routinely as in other connective tissues (13), and matrix metalloprotein-

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Section: Activity Of Prommps In Vitromentioning

confidence: 82%

Comparative study of the properties of tendinocytes derived from three different sites in the equine superficial digital flexor tendon

et al. 2010

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“…RNA was assessed by spectrophotometry at 260:280 nm and by 1% agarose gel electrophoresis. RNA was used for quantitative RT/PCR of collagen types I and III, 22,24 IGF-I, 25 and cartilage oligomeric matrix protein (COMP), [26][27][28] as indicators of tendon matrix synthesis, and matrix metalloproteinase-3 (MMP-3), [29][30][31] matrix metalloproteinase-13 (MMP-13), 24,29,32 and aggrecanase (ADAMTS-4) 30,33 as indicators of tendon catabolism.…”

Section: Rna Isolation and Quantitative Rt/pcrmentioning

confidence: 99%

Mesenchymal stem cells and insulin‐like growth factor‐I gene‐enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons

Schnabel

Lynch

Meulen

et al. 2009

Journal Orthopaedic Research

225

206

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Tendinitis remains a catastrophic injury among athletes. Mesenchymal stem cells (MSCs) have recently been investigated for use in the treatment of tendinitis. Previous work has demonstrated the value of insulin-like growth factor-I (IGF-I) to stimulate cellular proliferation and tendon fiber deposition in the core lesion of tendinitis. This study examined the effects of MSCs, as well as IGF-I geneenhanced MSCs (AdIGF-MSCs) on tendon healing in vivo. Collagenase-induced bilateral tendinitis lesions were created in equine flexor digitorum superficialis tendons (SDFT). Tendons were treated with 10 Â 10 6 MSCs or 10 Â 10 6 AdIGF-MSCs. Control limbs were injected with 1 mL of phosphate-buffered saline (PBS). Ultrasound examinations were performed at t ¼ 0, 2, 4, 6, and 8 weeks. Horses were euthanized at 8 weeks and SDFTs were mechanically tested to failure and evaluated for biochemical composition and histologic characteristics. Expression of collagen types I and III, IGF-I, cartilage oligomeric matrix protein (COMP), matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-13 (MMP-13), and aggrecanase-1 (ADAMTS-4) were similar in MSC and control tendons. Both MSC and AdIGF-MSC injection resulted in significantly improved tendon histological scores. These findings indicate a benefit to the use of MSCs and AdIGF-MSCs for the treatment of tendinitis. ß

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“…Levels of MMP-9 and MMP-13 peaked 7-14 days after injury, whereas MMP-2, MMP-3 and MMP-14 increased and were maintained at high levels until at least day 28 (Ref. 139). Thus, it appears that MMP-9 and MMP-13 are involved in the degradation of collagen in the initial inflammatory phase, whereas MMP-2, MMP-3 and MMP-14 have a role in the remodelling of the scar tissue.…”

Section: Mmps In Tendonmentioning

confidence: 99%

Chronic tendon pathology: molecular basis and therapeutic implications

Riley

2005

Expert Rev. Mol. Med.

103

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Tendons are frequently affected by chronic pain or rupture. Many causative factors have been implicated in the pathology, which until relatively recently was under-researched and poorly understood. There is now a greater knowledge of the molecular basis of tendon disease. Most tendon pathology (tendinopathy) is associated with degeneration, which is thought to be an active, cell-mediated process involving increased turnover and remodelling of the tendon extracellular matrix. Degradation of the tendon matrix is mediated by a variety of metalloproteinase enzymes, including matrix metalloproteinases and 'aggrecanases'. Neuropeptides and other factors released by stimulated cells or nerve endings in or around the tendon might influence matrix turnover, and could provide novel targets for therapeutic intervention.Tendons are dense, fibrous connective tissues that connect muscle to bone and are essential for the transmission of force and the generation of movement at a joint. They are highly ordered composite materials consisting of collagens, proteoglycans and various glycoproteins, many of which have been poorly characterised. Tendon problems such as tendon rupture and chronic tendon pain are common, although the underlying pathology is not well understood and the conditions are often difficult to treat (Ref.

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Flexor tendon healing in the rat: a histologic and gene expression study

Cited by 150 publications

References 16 publications

Comparative study of the properties of tendinocytes derived from three different sites in the equine superficial digital flexor tendon

Comparative study of the properties of tendinocytes derived from three different sites in the equine superficial digital flexor tendon

Mesenchymal stem cells and insulin‐like growth factor‐I gene‐enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons

Chronic tendon pathology: molecular basis and therapeutic implications

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