Peritendinous Tissue Research Articles

Diamond-Like Carbon Depositing on the Surface of Polylactide Membrane for Prevention of Adhesion Formation During Tendon Repair

HighlightsThe anti-adhesion effect of polylactic acid (PLA) membrane with diamond-like carbon (DLC) depositing is 44.72%, enhanced by 23.11% compared to PLA.DLC deposited on PLA membranes has been shown to effectively reduce the levels of reactive oxygen species, leading to a decrease in the expression of pro-inflammatory cytokines within peritendinous adhesion tissue.DLC decelerates PLA biodegradation and lactic production, which reduces the number of CD68+CD206+ macrophages within peritendinous adhesion tissue.

Unidirectional gene delivery electrospun fibrous membrane via charge repulsion for tendon repair

Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases. However, unidirectional targeting gene therapy is always desired at the tissue interface. In this study, inspired by the principle that like charges repulse each other, a positively charged micro-nano electrospun fibrous membrane with dual-layer structure was developed by electrospinning technology to achieve unidirectional delivery of siRNA-loaded cationic nanocarriers, thus realizing unidirectional gene therapy at the tendon-paratenon interface. Under the charge repulsion of positively charged layer, more cationic COX-2 siRNA nanocarriers were enriched in peritendinous tissue, which not only improved the bioavailability of the gene drug to prevent the peritendinous adhesion formation, but also avoided adverse effects on the fragile endogenous healing of tendon itself. In summary, this study provides an innovative strategy for unidirectional targeting gene therapy of tissue interface diseases by utilizing charge repulsion to facilitate unidirectional delivery of gene drugs.

Histological, Physiological and Biomechanical Effects of Low-Level Laser Therapy on Tendon Healing in Animals and Humans: A Systematic Review.

Low-level Laser Therapy (LLLT) was widely used in clinical practice for tendon disorders. However, the underlying mechanisms and effectiveness of LLLT in treating tendon injury remain unclear. Therefore, the present study was conducted aiming to summarize the evidence regarding the histological, physiological, and biomechanical effects of LLLT on tendon healing in animal and human models. Four databases were searched for relevant literature. Four independent reviewers screened abstracts and full-text articles, extracted relevant data, evaluated the risk of bias, and quantified the quality of evidence. Database searches yielded 1400 non-duplicated citations. Fifty-five studies were included (50 animal and five human studies). Animal studies revealed that LT had stimulating effects on collagen organization, collagen I and collagen II formation, matrix metalloproteinase (MMP)-8, transforming growth factor β1, vascular endothelial growth factor, hydroxyproline, maximum load, maximum elongation before breaking, and tendon stiffness. However, LLLT had inhibitory effects on the number of inflammatory cells, histological scores, relative amount of collagen III, cyclooxygenase-2, prostaglandin E2 (PGE2), interleukin-6, tumor necrosis factor-α, MMP-1, and MMP-3. Although one human study found that LLLT reduced the concentration of PGE2 in peritendinous tissue of the Achilles tendon, other human studies revealed that the effects of LLLT on the physiology and biomechanics of human tendons remained uncertain. LLLT facilitates tendon healing through various histological, physiological, and biomechanical effects in animal models. Only post-LLLT anti-inflammatory effects were found in human studies.

Is the Superficial Peritendinous Tissue an Additional Pain Driver in Patellar Tendinopathy?-Studies on Morphology and Innervation in a Case Series.

Background and Objectives: Ultrasound (US) and Doppler (DP) guided arthroscopic shaving targeting the area with neovessels and nerves on the dorsal side of the tendon has shown good clinical results. Recently, we observed that in a sub-group of patients there is also local tenderness on the superficial side of the proximal patellar tendon; Material and Methods: The aim was to examine morphology and innervation patterns of the superficial peritendinous tissue from patients (four men and two women; mean age 23 years, range 17–31 years) that on US+DP examination showed a locally thickened paratenon including high blood flow. Tissue sections were stained for morphology (hematoxylin and eosin, H&E) and immunohistochemically for nerve markers (β-tubulin; tyrosine hydroxylase, TH; calcitonin related gene peptide, CRGP); Results: All tissue specimens contained high levels of blood vessels and nerves (fascicles, sprouting nerve fibers, perivascular innervation) as evidenced by evaluation for H&E and β-tubulin reactions. Nerve fascicles mainly contained sensory but also sympathetic axons. Nerves related to blood vessels were sympathetic fibers; Conclusions: There was a marked innervation in the superficial peritendinous tissue in a sub-group of patients with patellar tendinopathy and severe tenderness in the proximal patellar tendon. The results indicate that this tissue might be an additional pain driver in some patients and should be considered in further studies.

Improving Imaging Modalities in Early Psoriatic Arthritis: The Role of Ultrasound in Early Diagnosis of Psoriatic Arthritis.

Objective: Despite recent advances, early diagnosis of psoriatic arthritis (PsA) remains a challenge in clinical practice. Ultrasound (US) could be a useful tool for the diagnosis and management of PsA. The objective of this review was to determine the role of US in early diagnosis of PsA.Methods: We have performed a literature review aiming to evaluate studies on US findings in psoriasis and their predictive value of progression to PsA, as well as studies on US features specific for PsA in comparison with other conditions.Results: A total of 40 studies were included. Sixteen studies assessed US findings in psoriasis, of which only 3 prospectively evaluated the role of US in predicting progression to PsA. Patients with PsA had a greater frequency of US abnormalities, in particular enthesitis and Power Doppler(PD) signal compared to patients with psoriasis only. In the longitudinal studies, psoriatic patients with higher enthesopathy scores at baseline were more likely to progress to PsA. Twenty-four studies evaluated US abnormalities in PsA and compared them to other conditions. Most specific US features that distinguish PsA from psoriasis were PD signal and erosions in joints and entheses. Extra-synovial changes, including peri-tendinous dermal soft tissue oedema with associated PD signal and flexor tendon enthesopathy, as well as thickening of the pulleys in the flexor tendons were highly characteristic for PsA, as they were frequently found in PsA patients, but in none of the RA patients. US-detected entheseal abnormalities in particular erosions and PD signal were more frequent in patients with PsA compared to fibromyalgia.Conclusion: Despite the wide use of US in PsA, more research is needed to identify predictive factors of progression to PsA in patients with psoriasis, as well as to determine most specific US features that differentiate PsA from other conditions.

Relationship between the ultrasonographic findings of suspected superficial digital flexor tendon injury and the prevalence of subsequent severe superficial digital flexor tendon injuries in Thoroughbred horses: a retrospective study.

The onset of severe injury to the superficial digital flexor tendon (SDFT) is extremely difficult to predict from slight changes in ultrasonographic findings in cases with no apparent clinical signs. This study investigated the relationship between an increased cross-sectional area (CSA) or edema in the subcutaneous tissue around the tendon and the subsequent onset of severe SDFT injury in Thoroughbred racehorses. Horses were classified into three groups based on ultrasound diagnosis (USD) findings: Group A included cases with enlarged tendons; Group B included cases with tendons of normal size but with prominent edema in the peritendinous tissue; and Group C (control group) included cases with no abnormal USD findings. The incidence of subsequent severe tendon injury was significantly higher in the horses in Groups A (25.7%, 28/101) and B (28.3%, 65/212) than in those in Group C (4.9%, 2/41). There were no significant differences in the median period and the median number of races from the first examination to the subsequent tendon injury between Groups A (140 days, 1 race) and B (120 days, 1 race). The results of this study revealed that horses with increased CSA and peritendinous edema are likely to suffer a subsequent severe tendon injury. Also, these two USD findings, i.e., increased CSA and peritendinous edema, indicate the risk of onset of severe SDFT injury.

Sequential inflammation model for Achilles tendinopathy by elastin degradation with treadmill exercise

Background & objectiveTendinopathy is a tendon disease with abnormal mechanical loading to induce chronic repetitive injury. However, lack of a comparable animal model to demonstrate clinical progressions has hindered the understanding of anatomical and pathological changes. The major extracellular matrix (ECM) in the tendon consists of abundant type I collagen (COL) and minimal amount of elastin (ELN). MethodsTo study the ECM breakdown and inflammation, rat Achilles tendon was harvested and ex vivo incubated with specific enzymes of elastase (ELNase) or collagenase (COLase). ResultsThe ELNase broke down ELN, loosened the tendon structure, and increased the COL composition. Increases in cyclooxygenase-2 expression levels in tenocytes were revealed to induce inflammation with either ELNase or COLase. However, incubation of COLase for 12 hours severely digested the tendon. To create a proper ELN degradation in rats, the present study used high-frequency ultrasound to guide the injection of ELNase at the paratendon tissue of the Achilles tendon. The effect of mechanically triggered inflammatory responses was investigated by applying treadmill exercise (15 m/min for 20 min per day). After ELNase injection for 14 and 28 days, a significant loss of ELN was observed, and exercise further facilitated the pathological transition of COL. The dynamics of inflammatory cell recruitments was revealed by specific staining of CD-11b (neutrophils) and CD-68 (macrophage) after in vivo injection of ELNase or COLase for 1, 3, 7, 14, and 28 days. The combination of ELNase and exercise caused early recruitment of neutrophil on day 1 and sequential expression of macrophage on day 7 in peritendinous tissue. ConclusionThese results suggested that ELN degradation with repetitive mechanical loading may present a suitable model for the pathogenesis of tendinopathy. The Translational potential of this articleThis discover the role of elastin degradation in tendinopathy and the interaction of exercise in the histological changes. The established the pathological model mimicking the pathogenesis to the human disease by injecting the elastase using ultrasound guidance and then applying treadmill exercise. The loss of elastin and change of collagen composition in clinical tendinopathy samples were observed in the rats. In addition, the sequential inflammation cascades were observed in the histological outcomes with combination of elastase injection and treadmill exercise. Thus, this model may be used to test the clinical treatment of tendinopathy in different stages.

Ultrasound findings in finger flexor tendons in systemic sclerosis: A cross-sectional pilot study.

Finger flexion contractures are an important cause of disability in patients with systemic sclerosis; however, their pathophysiology is poorly understood. Our aim was to assess the feasibility of scanning finger flexor tendons in patients with systemic sclerosis and explore the ultrasound findings in these tendons, including measurement of finger flexor tendon complex. Grey-scale and power Doppler ultrasound assessment of the finger flexor tendon complex including tendon structure and surrounding soft tissue. Measurements of the finger flexor tendon complex (A1 pulley, tendon and palmar plate) were made. Feasibility was assessed by the number of fingers which could be measured. We studied the second to fifth flexor tendons (n = 160) of both hands in 20 patients with systemic sclerosis, including early and established disease. We were able to assess the finger flexor tendon complex and make measurements of the flexor tendon and palmar plate in all (n = 40) and A1 pulley in almost all (n = 39) of the studied fingers. Common pathologies identified included peritendinous (n = 12) and soft tissue (n = 8) calcification. Tendon thickening was seen in six patients, but synovitis/tenosynovitis was rare. The A1 pulley was thickened in patients with systemic sclerosis (0.46 mm), in particular, those with diffuse cutaneous systemic sclerosis (0.50 mm). We were able to successfully assess, including making measurements of, the finger flexor tendon complex in patients with systemic sclerosis. Our study showed calcifications in the peritendinous areas and soft tissue and thickening of the A1 pulley. These findings may play a role in the pathophysiology of systemic sclerosis-hand contractures by causing mechanical impingement of the finger flexion mechanism. This pilot study will guide future research to look for potential (treatable) causes of finger flexion contractures in patients with systemic sclerosis.

Hydroxycamptothecin Prevents Fibrotic Pathways in Fibroblasts In Vitro.

Peritendinous fibrosis, which leads to impaired tendon function, is a clinical problem worldwide, and it is urgent to explore potential ways to reduce the formation of peritendinous adhesion. Several studies have demonstrated the biological roles of hydroxycamptothecin (HCPT) in inhibiting fibrosis in different tissues. In this study, we investigated whether HCPT could inhibit tendon fibrosis in vitro. Our results revealed that HCPT inhibited transforming growth factor (TGF)-β1-induced cell viability of human fibroblasts, decreased excessive cell hyperproliferation and promoted fibroblasts apoptosis. In addition, HCPT treatment also inhibited expression of fibrosis genes COL3A1 and α-smooth muscle actin (α-SMA). In terms of mechanism, we pretreated fibroblasts with the endoplasmic reticulum stress (ER) inhibitor salubrinal and RNA-dependent protein kinase-like ER kinase (PERK) short hairpin RNA, these treatments abolished the inhibitory effects of HCPT on fibrosis, thereby suggesting that HCPT's inhibition of TGF-β1-induced tendon fibrosis might be mediated by the PERK signaling pathway in vitro. In conclusion, our results suggested that HCPT had protective effects on peritendinous tissue fibrosis and might be promising in future clinical applications. © 2019 IUBMB Life, 71(5):653-662, 2019.

Macrophage-Derived miRNA-Containing Exosomes Induce Peritendinous Fibrosis after Tendon Injury through the miR-21-5p/Smad7 Pathway

Following tendon injury, the development of fibrotic healing response impairs tendon function and restricts tendon motion. Peritendinous tissue fibrosis poses a major clinical problem in hand surgery. Communication between macrophages and tendon cells has a critical role in regulating the tendon-healing process. Yet, the mechanisms employed by macrophages to control peritendinous fibrosis are not fully understood. Here we analyze the role of macrophages in tendon adhesion in mice by pharmacologically depleting them. Such macrophage-depleted mice have less peritendinous fibrosis formation around the injured tendon compared with wild-type littermates. Macrophage-depleted mice restart fibrotic tendon healing by treatment with bone marrow macrophage-derived exosomes. We show that bone marrow macrophages secrete exosomal miR-21-5p that directly targets Smad7, leading to the activation of fibrogenesis in tendon cells. These results demonstrate that intercellular crosstalk between bone marrow macrophages and tendon cells is mediated by macrophage-derived miR-21-5p-containing exosomes that control the fibrotic healing response, providing potential targets for the prevention and treatment of tendon adhesion.

Metformin prevents peritendinous fibrosis by inhibiting transforming growth factor-β signaling

Injury-induced peritendinous adhesion is a critical clinical problem that leads to tendon function impairment. Therefore, it is very urgent to explore potential approaches to attenuate peritendinous adhesion formation. Recently, several studies have demonstrated the biological effect of metformin in inhibiting multiple tissue fibrosis. In this study, we performed in vitro and in vivo experiments to examine whether metformin prevents injury-induced peritendinous fibrosis. We found that tendon injury induced severe fibrosis formation in rats. However, orally administered metformin significantly alleviated the fibrosis based on macroscopic and histological evaluation. Peritendinous tissue from metformin-treated rats also showed decreased expression of fibrotic genes including col1a1, col3a1, and α-smooth muscle actin (α-SMA), and inhibition of transforming growth factor (TGF)-β1 signaling. The cell counting kit (CCK)-8, flow cytometry, and 5-ethynyl-2′-deoxyuridine (EdU) staining analyses showed that treatment of NIH/3T3 fibroblasts with metformin significantly inhibited excessive cell proliferation and promoted cell apoptosis. Metformin treatment also inhibited the expression of fibrotic genes and decreased the phosphorylation of smad2/3 and extracellular signal-regulated kinase (ERK) 1/2. Furthermore, blocking AMP-activated protein kinase (AMPK) signaling abolished the inhibitory effect of metformin on fibrosis. Our findings indicate that metformin has a protective role against peritendinous tissue fibrosis and suggest its clinical use could be a promising therapeutic approach.

RelA/p65 inhibition prevents tendon adhesion by modulating inflammation, cell proliferation, and apoptosis

Peritendinous tissue fibrosis which leads to poor tendon function is a worldwide clinical problem; however, its mechanism remains unclear. Transcription factor RelA/p65, an important subunit in the NF-κB complex, is known to have a critical role in many fibrotic diseases. Here, we show that RelA/p65 functions as a core fibrogenic regulator in tendon adhesion and that its inhibition exerts an anti-fibrogenic effect on peritendinous adhesion. We detected the upregulation of the NF-κB pathway in human tendon adhesion using a gene chip microarray assay and revealed the overexpression of p65 and extracellular matrix (ECM) proteins Collagen I, Collagen III, and α-smooth muscle actin (α-SMA) in human fibrotic tissues by immunohistochemistry and western blotting. We also found that in a rat model of tendon injury, p65 expression correlated with tendon adhesion, whereas its inhibition by small interfering (si)RNA prevented fibrous tissue formation and inflammatory reaction as evidenced by macroscopic, biomechanical, histological, immunohistochemical, and western blotting analyses. Furthermore, in cultured fibroblasts, p65-siRNA, p65-specific inhibitor, Helenalin and JSH23 suppressed cell proliferation and promoted apoptosis, whereas inhibiting the mRNA and protein expression of ECM components and cyclo-oxygenase-2, an inflammatory factor involved in tendon adhesion. Our findings indicate that p65 has a critical role in peritendinous tissue fibrosis and suggest that p65 knockdown may be a promising therapeutic approach to prevent tendon adhesion.

Plantaris Excision Reduces Pain in Midportion Achilles Tendinopathy Even in the Absence of Plantaris Tendinosis.

Background:It is becoming increasingly apparent that the plantaris can contribute to symptoms in at least a subset of patients with midportion Achilles tendinopathy. However, the nature of its involvement remains unclear.Purpose:To determine whether excised plantaris tendons from patients with midportion Achilles tendinopathy display tendinopathic changes and whether the presence of such changes affect clinical outcomes.Study Design:Case series; Level of evidence, 4.Methods:Sixteen plantaris tendons in patients with midportion Achilles tendinopathy recalcitrant to conservative management underwent histological examination for the presence of tendinopathic changes. All patients had imaging to confirm the presence of the plantaris tendon adherent to or invaginated into the focal area of Achilles tendinosis. Visual analog scale (VAS) and Foot and Ankle Outcome Score (FAOS) results were recorded pre- and postoperatively.Results:Sixteen patients (mean age, 26.2 years; range, 18-47 years) underwent surgery, with a mean follow-up of 14 months (range, 6-20 months). The plantaris tendon was histologically normal in 13 of 16 cases (81%). Inflammatory changes in the loose peritendinous connective tissue surrounding the plantaris tendon were evident in all cases. There was significant improvement in mean VAS scores (P < .05) and all domains of the FAOS postoperatively (P < .05).Conclusion:The absence of any tendinopathic changes in the excised plantaris of 13 patients who clinically improved suggests plantaris involvement with Achilles tendinopathy may not yet be fully understood and supports the concept that this may be a compressive or a frictional phenomenon rather than purely tendinopathic.

Assessment of the Postoperative Appearance of the Rotator Cuff Tendon Using Serial Sonography After Arthroscopic Repair of a Rotator Cuff Tear.

The purpose of this study was to evaluate serial changes in sonographic findings of a rotator cuff tendon after rotator cuff repair. Sixty-five arthroscopically repaired rotator cuff tears (43 full-thickness tears and 22 partial-thickness tears) were retrospectively included in this study. Serial sonographic examinations were performed at 5 weeks, 3 months, and 6 months after surgery. The sonographic findings of the repaired tendon were assessed for a recurrent tear, tendon thickness, morphologic tendon characteristics, vascularity, and bursitis at each time point. Four recurrent tears occurred within 3 months of surgery. The postoperative tendon thickness decreased from 5 weeks to 6 months after surgery (P = .001). There were significant changes in the morphologic tendon characteristics, including the echo texture, fibrillar pattern, and surface irregularity of the repaired tendon, from 5 weeks to 6 months after surgery (P < .001). Additionally, subacromial-subdeltoid bursitis and the vascularity of the repaired tendon decreased postoperatively over time. Serial sonography after arthroscopic rotator cuff repair was useful for monitoring the postoperative changes in a repaired tendon. The morphologic appearance of the repaired tendon and peritendinous soft tissue changes improved over time and nearly normalized within 6 months of surgery.

Further proof of the existence of a non-neuronal cholinergic system in the human Achilles tendon: Presence of the AChRα7 receptor in tendon cells and cells in the peritendinous tissue

Human tendon cells have the capacity for acetylcholine (ACh) production. It is not known if the tendon cells also have the potential for ACh breakdown, nor if they show expression of the nicotinic acetylcholine receptor AChRα7 (α7nAChR). Therefore, tendon tissue specimens from patients with midportion Achilles tendinopathy/tendinosis and from normal midportion Achilles tendons were examined. Reaction for the degradative enzyme acetylcholinesterase (AChE) was found in some tenocytes in only a few tendinopathy tendons, and was never found in those of control tendons. Tenocytes displayed more regularly α7nAChR immunoreactivity. However, there was a marked heterogeneity in the degree of this reaction within and between the specimens. α7nAChR immunoreactivity was especially pronounced for tenocytes showing an oval/widened appearance. There was a tendency that the magnitude of α7nAChR immunoreactivity was higher in tendinopathy tendons as compared to control tendons. A stronger α7nAChR immunoreactivity than seen for tenocytes was observed for the cells in the peritendinous tissue. It is likely that the α7nAChR may be an important part of an auto-and paracrine loop of non-neuronal ACh that is released from the tendon cells. The effects may be related to proliferative and blood vessel regulatory functions as well as features related to collagen deposition. ACh can furthermore be of importance in leading to anti-inflammatory effects in the peritendinous tissue, a tissue nowadays considered to be of great relevance for the tendinopathy process. Overall, the findings show that tendon tissue, a tissue known to be devoid of cholinergic innervation, is a tissue in which there is a marked non-neuronal cholinergic system.

Down-regulating ERK1/2 and SMAD2/3 phosphorylation by physical barrier of celecoxib-loaded electrospun fibrous membranes prevents tendon adhesions

Peritendinous adhesions, as a major problem in hand surgery, may be due to the proliferation of fibroblasts and excessive collagen synthesis, in which ERK1/2 and SMAD2/3 plays crucial roles. In this study, we hypothesized that the complication progression could be inhibited by down-regulating ERK1/2 and SMAD2/3 phosphorylation of exogenous fibroblasts with celecoxib. Celecoxib was incorporated in poly(l-lactic acid)-polyethylene glycol (PELA) diblock copolymer fibrous membranes via electrospinning. Results of an in vitro drug release study showed celecoxib-loaded membrane had excellent continuous drug release capability. It was found that celecoxib-loaded PELA membranes were not favorable for the rabbit fibroblast and tenocyte adhesion and proliferation. In a rabbit tendon repair model, we first identified ERK1/2 and SMAD2/3 phosphorylation as a critical driver of early adhesion formation progression. Celecoxib released from PELA membrane was found to down-regulate ERK1/2 and SMAD2/3 phosphorylation, leading to reduced collagen I and collagen Ⅲ expression, inflammation reaction, and fibroblast proliferation. Importantly, the celecoxib-loaded PELA membranes successfully prevented tissue adhesion compared with control treatment and unloaded membranes treatment. This approach offers a novel barrier strategy to block tendon adhesion through targeted down-regulating of ERK1/2 and SMAD2/3 phosphorylation directly within peritendinous adhesion tissue.

A trochanteric sparing technique for stem removal in revision hip arthroplasty.

DISCUSSION Previous reports have described techniques to administer local anaesthetic to the hamstrings tendon bed via the harvest tract after graft harvest. In these descriptions, the injection was given via a blunt device such as a suction catheter or arthroscopic shaver sleeve into the donor site space, without image guidance. The use of ultrasonography guidance allows anaesthetic to be introduced to the target site with improved accuracy. In addition, it allows the safe use of a hypodermic needle, allowing peritendinous tissue infiltration rather than simple filling of a dead space. We have performed this technique without complication in 14 patients. Postoperative pain scores were uniformly low and all were discharged successfully as day cases.

SAT0170 Ultrasound Composite Score for the Assessment of Inflammatory and Structural Pathologies in Psoriatic Arthritis

BackgroundIn clinical trials and routine practice of Psoriatic arthritis (PsA), disease activity is still monitored by RA specific clinical composites even if these measures are of questionable value for the...

Tenosinovitis with psammomatous calcification – a case report

Tenosynovitis with psammomatous calcification, described in 1983 by Gravanis and Gaffney, is poorly recognized by pathologists. Recently, tenosynovitis with psammomatous calcification differ from those of typical idiopathic calcifying tenosynovitis/calcific tendinitis and tumoral calcinosis, were reported based on the analysis of 6 cases. We report a 36-year-old man with tenosynovitis with psammomarous calcification involving the palmar side of the proximal interphalangeal (PIP) joint at left middle finger. He had been suffered from a slow growing painful mass at left finger for three weeks. He had not a history of persistent mild trauma and hyperphosphatemia. X-ray examination revealed ill-demarcated calcifying mass 5mm in diameter. The lesion, treated by surgical excision, was elastic soft and white-yellow mass on the volar plate of the PIP joint extending to the intraarticular space. Histologically, the lesion was centered in the tendon or peritendinous soft tissue and composed of a mixed fibroblastic and histiocytic proliferation with the formation of distinctive psammoma body-like spheroidal bodies.

Experimental Diabetes Induces Structural, Inflammatory and Vascular Changes of Achilles Tendons

This study aims to demonstrate how the state of chronic hyperglycemia from experimental Diabetes Mellitus can influence the homeostatic imbalance of tendons and, consequently, lead to the characteristics of tendinopathy. Twenty animals were randomly divided into two experimental groups: control group, consisting of healthy rats and diabetic group constituted by rats induced to Diabetes Mellitus I. After twenty-four days of the induction of Diabetes type I, the Achilles tendon were removed for morphological evaluation, cellularity, number and cross-sectional area of blood vessel, immunohistochemistry for Collagen type I, VEGF and NF-κB nuclear localization sequence (NLS) and nitrate and nitrite level. The Achilles tendon thickness (µm/100g) of diabetic animals was significantly increased and, similarly, an increase was observed in the density of fibrocytes and mast cells in the tendons of the diabetic group. The average number of blood vessels per field, in peritendinous tissue, was statistically higher in the diabetic group 3.39 (2.98) vessels/field when compared to the control group 0.89 (1.68) vessels/field p = 0.001 and in the intratendinous region, it was observed that blood vessels were extremely rare in the control group 0.035 (0.18) vessels/field and were often present in the tendons of the diabetic group 0.89 (0.99) vessels/field. The immunohistochemistry analysis identified higher density of type 1 collagen and increased expression of VEGF as well as increased immunostaining for NFκB p50 NLS in the nucleus in Achilles tendon of the diabetic group when compared to the control group. Higher levels of nitrite/nitrate were observed in the experimental group induced to diabetes. We conclude that experimental DM induces notable structural, inflammatory and vascular changes in the Achilles tendon which are compatible with the process of chronic tendinopathy.