Uncorrelated healing response of tendon and ear injuries in MRL highlight a role for the local tendon environment in driving scarless healing.

PURPOSE: Tendon tears are common injuries that heal with scar formation. Interestingly, MRL/MpJ mice heal without scar in several tissues, including tendon. Most hypotheses regarding scarless healing implicate the systemic environment. However, the tissue-specificity of this regenerative response and our previous findings showing regeneration of sub-rupture tendon injuries, which lack an overt systemic response, motivate a tissue-driven hypothesis. Our objective is to investigate the potential of the local tendon environment in driving scarless healing (1) by comparing the systemic response and the healing capacity associated with ear and tendon injuries in MRL/MpJ mice, and (2) by comparing intrinsic healing properties between MRL/MpJ and normal healer C57Bl/6 tendons. METHODS: We examined the systemic inflammatory and local structural environments of ear and tendon punch injuries in MRL/MpJ and C57Bl/6 mice. Systemic differences were analyzed to assess effects of different injuries on the inflammatory response. Correlations were assessed between MRL/MpJ ear and tendon injuries to compare the extent of healing between regenerative tissues. RESULTS: Analysis showed similarities between the systemic environment in MRL/MpJ post ear or tendon injuries. However, comparable inflammatory responses did not translate into analogous healing between tissues, suggesting that the systemic environment is not the driver of regeneration. Supporting the regenerative role of the local environment, healing MRL/MpJ tendons exhibited improved matrix and cell alignment and a distinct composition of growth factors and Hyaluronan from C57Bl/6. CONCLUSION: These findings support the tissue-driven hypothesis for MRL/MpJ tendon regeneration and motivate further investigation regarding specific roles of extracellular factors in scarless healing.

Low-level laser therapy modulates pro-inflammatory cytokines after partial tenotomy.

Tendon injuries give rise to substantial morbidity, and current understanding of the mechanisms involved in tendon injury and repair is limited. This lesion remains a clinical issue because the injury site becomes a region with a high incidence of recurrent rupture and has drawn the attention of researchers. We already demonstrated that low-level laser therapy (LLLT) stimulates the synthesis and organization of collagen I, MMP-9, and MMP-2 and improved the gait recovery of the treated animals. The aim of this study was to evaluate the effects of LLLT in the nitric oxide and cytokines profile during the inflammatory and remodeling phases. Adult male rats were divided into the following groups: G1--intact, G2-- injured, G3--injured + LLLT (4 J/cm(2) continuous), G4--injured + LLLT (4 J/cm(2)-20 Hz--pulsed laser). According to the analysis, the animals were euthanized on different dates (1, 4, 8, or 15 days after injury). ELISA assay of TNF-α, IL-1ß, IL-10, and TGF-ß was performed. Western blotting of isoform of nitric oxide synthase (i-NOS) and nitric oxide dosage experiments was conducted. Our results showed that the pulsed LLLT seems to exert an anti-inflammatory effect over injured tendons, with reduction of the release of proinflammatory cytokines, such as TNF-α and the decrease in the i-NOS activity. Thanks to the pain reduction and the facilitation of movement, there was a stimulation in the TGF-ß and IL-1ß release. In conclusion, we believe that pulsed LLLT worked effectively as a therapy to reestablish the tendon integrity after rupture.

Is higher serum cholesterol associated with altered tendon structure or tendon pain? A systematic review.

BACKGROUND: Tendon pain occurs in individuals with extreme cholesterol levels (familial hypercholesterolaemia). It is unclear whether the association with tendon pain is strong with less extreme elevations of cholesterol. OBJECTIVE: To determine whether lipid levels are associated with abnormal tendon structure or the presence of tendon pain. METHODS: We conducted a systematic review and meta-analysis. Relevant articles were found through an electronic search of 6 medical databases-MEDLINE, Cochrane, AMED, EMBASE, Web of Science and Scopus. We included all case-control or cross-sectional studies with data describing (1) lipid levels or use of lipid-lowering drugs and (2) tendon structure or tendon pain. RESULTS: 17 studies (2612 participants) were eligible for inclusion in the review. People with altered tendon structure or tendon pain had significantly higher total cholesterol, low-density lipoprotein cholesterol and triglycerides, as well as lower high-density lipoprotein cholesterol; with mean difference values of 0.66, 1.00, 0.33, and -0.19 mmol/L, respectively. CONCLUSIONS: The results of this review indicate that a relationship exists between an individual's lipid profile and tendon health. However, further longitudinal studies are required to determine whether a cause and effect relationship exists between tendon structure and lipid levels. This could lead to advancement in the understanding of the pathoaetiology and thus treatment of tendinopathy.

Relationship of ABO Blood Type on Rotator Cuff Tears.

BACKGROUND: ABO blood groups are associated with various diseases. A relationship between Achilles tendon ruptures and blood type O has been reported, although its pathogenesis was not clear. To the best of our knowledge, there is no published study describing the relationship between blood type and rotator cuff tendon tears. OBJECTIVE: To determine whether patients with rotator cuff tear had a greater prevalence of blood type O than those without rotator cuff tear. DESIGN: A cross-sectional study. SETTING: Research hospital outpatient evaluation. PARTICIPANTS: A total of 316 subjects with shoulder pain were included and divided into "tear" and "no-tear" groups according to ultrasonographic examination. MAIN OUTCOME MEASURES: ABO blood group, gender, dominant arm, smoking history, trauma history, and age were compared between the 2 groups and the odds ratios of these factors were evaluated by logistic regression. RESULTS: The tear group (38.6%) had more instances of blood type O than the healthy population (27.2%; P = .002). The adjusted odds ratio for rotator cuff tear for blood type O to non-O was 2.38 (95% confidence interval 1.28-4.42). The odds ratios for rotator cuff tears for smoking, major trauma history, minor trauma history, and age were 2.08, 3.11, 2.29, and 1.06, respectively. CONCLUSION: Patients with rotator cuff tears were more likely to have blood type O. The odds ratios of factors for rotator cuff tears were high in the following order: major trauma history, blood type O, minor trauma history, and age.

Synthesis, development, characterization and effectiveness of bovine pure platelet gel-collagen-polydioxanone bioactive graft on tendon healing.

Bovine platelet gel (BPG) is an accessible and cost-effective source of growth factors which may have a value in tendon regenerative medicine. We produced a collagen implant (CI) as a tendon proper, covered it with polydioxanone (PDS) sheath to simulate paratenon and finally embedded the BPG as an active source of growth factor within the bioimplant to test whether BPG would be able to accelerate and enhance tendon regeneration and repair. After in vitro characterization of the bioactive grafts, the grafts were implanted in rabbit large tendon defect model. Untreated tendons and tendons treated with either CI or CI-PDS were served as controls for the CI-PDS-BPG. The animals were investigated clinically, ultrasonographically and haematologically for 120 days. After euthanasia, dry matter content, water uptake and delivery characteristics and also gross morphological, histopathological and scanning electron microscopic features of the healing tendons were assessed. In vitro, the activated platelets in the scaffold, released their growth factors significantly more than the controls. BPG also increased cell viability, and enhanced cellular differentiation, maturation and proliferation inside the CI-PDS compared with the controls. In vivo, the BPG modulated inflammation, increased quality and rate of fibroplasia and produced a remodelled tendon that had significantly higher collagen content and superior collagen fibril and fibre differentiation than controls. Treatment also significantly improved tendon water uptake and delivery characteristics, animals' serum PDGF level, CI-PDS biocompatibility and biodegradability and reduced peritendinous adhesions, muscle fibrosis and atrophy. BPG was effective on tendon healing and CI-PDS-BPG may be a valuable bioscaffold in tendon reconstructive surgery.

Sustained release of tissue factor following thrombosis of lower limb trauma.

This study was undertaken to provide evidence for the mechanism of venous thromboembolism (VTE) in healthy patients with minor lower limb injury (fracture; Achilles tendon rupture) that was medically managed with plaster cast/brace immobilization. The Plaster Cast clinical trial provided a unique opportunity to identify the natural history of VTE using placebo-controlled patients (n = 183) with validation of the mechanism using the low-molecular-weight heparin (LMWH; reviparin)-treated patients (n = 182). Confirmed VTE in this population was associated with a burst of tissue factor release (and a minor fibrinolytic deficit) leading to thrombin generation that was sustained at least 5 weeks, greater with fractures than with soft-tissue injuries and greater with surgery than with conservative treatment. The root cause likely involves platelet/leukocyte activation (inflammation) rather than endothelial cell injury. Thromboprophylaxis with a low dose of LMWH reduced thrombin generation, with patients undergoing surgery benefitting the most.

Prevalence of and risk factors for asymptomatic rotator cuff tears in postmenopausal women.

OBJECTIVE: Rotator cuff tendon tears increase with age, but no study has specifically addressed prevalence changes in women from premenopause to postmenopause. The aims of this study were to evaluate the prevalence of rotator cuff asymptomatic tears in postmenopausal women and to study their relationship with anthropometric and metabolic measures. METHODS: Premenopausal and postmenopausal women who were free from shoulder pain/functional impairment were enrolled. Body mass index (BMI), fasting glucose, triglycerides, total cholesterol, and high-density lipoprotein (HDL) cholesterol were evaluated. Both shoulders were examined by ultrasound imaging. For the purposes of this study, only full-thickness tears (classified as small, large, or massive) were taken into account. RESULTS: The prevalence of full-thickness tears (mainly localized in the supraspinatus tendon of the dominant side) was significantly higher in the postmenopausal group (8.9% vs 3.1%), with small, medium, and large tears in 60%, 20%, and 20% of cases, respectively. In women with tears, intragroup comparison showed significantly higher values for BMI and fasting glucose, and lower levels of HDL cholesterol; no difference was found for triglycerides and total cholesterol in premenopausal and postmenopausal women, respectively. On multiple logistic regression analysis, the probability of detecting a tear in both groups was positively related to high values of BMI and lower levels of HDL cholesterol. CONCLUSIONS: The prevalence of asymptomatic full-thickness tears is increased in the postmenopausal period, and there is an association between tears and metabolic disorders. Because asymptomatic tears have a great potential to evolve into symptomatic painful shoulder, a precocious discovery of this pathology may allow the planning of preventive and therapeutic measures.

Equine tendonitis therapy using mesenchymal stem cells and platelet concentrates: a randomized controlled trial.

INTRODUCTION: Tendon injury is a major cause of lameness and decreased performance in athletic equines. Various therapies for tendonitis have been described; however, none of these therapies results in complete tissue regeneration, and the injury recurrence rate is high even after long recovery periods involving rest and physiotherapy. METHODS: A lesion was induced with collagenase gel in the superficial digital flexor tendon in the center portion of the metacarpal region of eight equines of mixed breed. After two weeks, the lesions of the animals in the treated and control groups were treated through the intralesional administration of mesenchymal stem cells derived from adipose tissue (adMSCs) suspended in platelet concentrate (PC) and with phosphate buffered saline (PBS), respectively. Serial ultrasound analyses were performed every two weeks. After 16 weeks of therapy, a biopsy was performed for histopathological, immunohistochemical and gene expression (type I collagen (COL1A1), type III collagen (COL3A1), tenascin-C (TNC), tenomodulin (TNMD), and scleraxis (SCX)) analyses. RESULTS: Differences in the ultrasound and histopathological analyses were observed between the groups. Improved results were reported in the group treated with adMSCs suspended in PC. There was no difference in the gene expression levels observed after the different treatments. The main results observed from the histopathological evaluation of the treated group were as follows: a prevention of the progression of the lesion, a greater organization of collagen fibers, and a decreased inflammatory infiltrate. A lack of progression of the lesion area and its percentage was observed in the ultrasound image, and increased blood flow was measured by Power Doppler. CONCLUSIONS: The use of adMSCs combined with PC for the therapy of experimentally induced tendonitis prevented the progression of the tendon lesion, as observed in the ultrasound examination, and resulted in a greater organization and decreased inflammation, as observed in the histopathological evaluation. These data demonstrate the therapeutic potential of this therapy for the treatment of equine tendonitis.

Elevated plasma levels of TIMP-1 in patients with rotator cuff tear.

BACKGROUND AND PURPOSE: Extracellular matrix remodeling is altered in rotator cuff tears, partly due to altered expression of matrix metalloproteinases (MMPs) and their inhibitors. It is unclear whether this altered expression can be traced as changes in plasma protein levels. We measured the plasma levels of MMPs and their tissue inhibitors (TIMPs) in patients with rotator cuff tears and related changes in the pattern of MMP and TIMP levels to the extent of the rotator cuff tear. METHODS: Blood samples were collected from 17 patients, median age 61 (39-77) years, with sonographically verified rotator cuff tears (partial- or full-thickness). These were compared with 16 age- and sex-matched control individuals with sonographically intact rotator cuffs. Plasma levels of MMPs and TIMPs were measured simultaneously using Luminex technology and ELISA. RESULTS: The plasma levels of TIMP-1 were elevated in patients with rotator cuff tears, especially in those with full-thickness tears. The levels of TIMP-1, TIMP-3, and MMP-9 were higher in patients with full-thickness tears than in those with partial-thickness tears, but only the TIMP-1 levels were significantly different from those in the controls. INTERPRETATION: The observed elevation of TIMP-1 in plasma might reflect local pathological processes in or around the rotator cuff, or a genetic predisposition in these patients. That the levels of TIMP-1 and of certain MMPs were found to differ significantly between partial and full-thickness tears may reflect the extent of the lesion or different etiology and pathomechanisms.

Prospective correlation between serum relaxin concentration and anterior cruciate ligament tears among elite collegiate female athletes.

BACKGROUND: The female anterior cruciate ligament may be more susceptible to injury than the male anterior cruciate ligament because of the gender-specific expression of receptors for relaxin, a collagenolytic hormone that promotes remodeling of the anterior cruciate ligament. PURPOSE: This study was undertaken to investigate whether collegiate female athletes with elevated serum relaxin concentrations (SRC) sustain anterior cruciate ligament tears at an increased rate compared with those with lower SRC. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2. METHODS: From 2005 to 2010, 143 Division I female athletes from 2 universities participating in sports at high risk for anterior cruciate ligament tears (basketball, lacrosse, field hockey, soccer, gymnastics, and volleyball) were recruited to participate. Questionnaires and urine luteinizing hormone (LH) tests were used to determine participants' anterior cruciate ligament injury and menstrual history and to identify their mid-luteal phase or projected cycle days 21 to 24. Serum samples were obtained for progesterone and relaxin ELISA (enzyme-linked immunosorbent assay) analysis. Participants were monitored for anterior cruciate ligament injury over their 4-year National Collegiate Athletic Association athletic career. RESULTS: A total of 128 participants completed the study and were eligible for data analysis. The cumulative incidence of complete anterior cruciate ligament tear over the 4-year study period was 21.9%, and varied significantly by sport (P < .001). The mean SRC for athletes with anterior cruciate ligament tears (6.0 ± 8.1 pg/mL) was significantly higher than that for those without anterior cruciate ligament tears (1.8 ± 3.4 pg/mL; P = .013). In subgroup analysis of the 46 athletes who had detectable SRC, the cumulative incidence of anterior cruciate ligament tear was 14 of 46 (30.4%); the mean SRC among athletes with anterior cruciate ligament tears (14 of 46) was 12.1 ± 7.7 pg/mL and without anterior cruciate ligament tears (32 of 46), 5.7 ± 3.6 pg/mL (P = .002). When 6.0 pg/mL was set as the SRC cutoff for screening athletes for risk of anterior cruciate ligament tear in the subgroup with detectable relaxin levels, the test had 71% sensitivity, 69% specificity, 52% positive predictive value, 88% negative predictive value, and a relative risk of 4.4. These values were significant by χ(2) test (P = .003) and receiver operating characteristic analysis (P = .002). CONCLUSION: Elite female athletes with anterior cruciate ligament tears have higher SRC than those without tears. Those with an SRC greater than 6.0 pg/mL had over 4 times increased risk for a tear. CLINICAL RELEVANCE: Females with higher serum relaxin levels may be at increased risk for anterior cruciate ligament tears. Further investigation of the clinical utility of SRC testing is warranted.

The effect of hypercholesterolemia on rotator cuff disease.

BACKGROUND: The causes of rotator cuff tendon rupture are multifactorial and still unclear. Intrinsic and extrinsic factors have been implicated as predisposing risk factors for rotator cuff rupture. Previous studies have suggested a relationship between elevated serum lipid profiles and tendon ruptures, although not rotator cuff tears specifically. QUESTIONS/PURPOSES: We therefore asked whether patients with rotator cuff tears were more likely to have higher levels of hypercholesterolemia than patients with shoulder pain but without tears. METHODS: We prospectively collected serum cholesterol and lipid profiles on two age-matched populations of patients; 74 (mean age, 66.3 years) had ruptures of their rotator cuff tendons, whereas a control group of 73 patients (mean age, 67.4 years) were seen for nontendon-related shoulder complaints. RESULTS: Total cholesterol, triglycerides, and low-density lipoprotein cholesterol concentrations of the patients with rotator cuff tendon tears were higher, and their high-density lipoprotein cholesterol showed a trend to being lower than the control group. Forty-seven of 74 patients (63%) with rotator cuff tears had an elevated serum cholesterol (total cholesterol greater than 240 mg/dL) as compared with an overall rate of 28% in our control group. CONCLUSIONS: Patients with rotator cuff tears were more likely to have hypercholesterolemia when compared with the control group. CLINICAL RELEVANCE: Measurement of serum cholesterol in patients presenting with torn rotator cuff tendons should be considered in patients whose cholesterol profiles are unknown. Future consideration of drug treatment may reduce risk for future tendon degeneration, as well as improve quality of life and reduce mortality. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Triglycerides and total serum cholesterol in rotator cuff tears: do they matter?

OBJECTIVE: In this study, the serum triglycerides and total serum cholesterol levels in patients with rotator cuff tear were determined. DESIGN: Frequency-matched case-control study. Setting University teaching hospital. PARTICIPANTS: 240 individuals who were operated on at our institution were included in the study. 120 patients (45 men and 75 women; mean age 64.86 years, range 40 to 83 years) who underwent arthroscopic repair of a rotator cuff tear were included in group 1. 120 patients (45 men and 75 women; mean age 63.91 years, range 38 to 78 years) who underwent arthroscopic meniscectomy for a meniscal tear and had no evidence of shoulder pathology were included in group 2 (control group). These patients were frequency-matched by age (within 3 years) and sex with patients of group 1. MAIN OUTCOME MEASURES: Measurement of serum triglyceride and total cholesterol concentrations. RESULTS: When comparing the two groups, there was no difference either in serum triglyceride concentration or total serum cholesterol concentration. CONCLUSIONS: There appears to be no association between serum triglyceride concentration and total serum cholesterol concentration in rotator cuff tears.

Biomechanical and histological comparison of the influence of oestrogen deficient state on tendon healing potential in rats.

Thirty-six female Sprague-Dawley rats were divided into two groups: oophrectomised (oestrogen deficient) rats and sham operated (oestrogen maintained) rats. Rats were sacrificed at six, ten, and 14 weeks. The rats were randomly chosen to have biomechanical evaluation on one side and histological evaluation on the other. Biomechanical testing was performed on an Instron machine to measure peak load. Histological sections were evaluated for cell proliferation, collagen-fibre organisation, fibroblast density, angiogenesis, inflammatory cells, chondroid and osseous metaplasia. Compared with the sham operated group, the oophrectomised group showed a lesser average maximum stress (42.9 N/m(2) versus 33.7 N/m(2)) at six weeks, which was significant (p < .05). Succeeding weeks showed no significant biomechanical differences between the two groups. The sham operated group showed greater inflammatory response, which was statistically significant (p < 0.05), and also revealed greater cell proliferation and density. The results of this study revealed that endogenous oestrogen may improve healing of the Achilles tendon in rats.

Treatment of tendon and muscle using platelet-rich plasma.

Tendon and muscle injuries are common in elite and weekend athletes. Treatment of these injuries in both groups is rapidly evolving. Sports medicine patients are demanding better and less invasive solutions for all types of musculoskeletal disorders. In this context, platelet-rich plasma (PRP) has emerged as a potential solution. PRP is a fraction of whole blood containing concentrated growth factors and proteins. These cytokines direct tissue healing through autocrine and paracrine effects. The number of basic science, animal, and human investigations of PRP for tendon and muscle injuries worldwide has risen sharply in recent years. These studies are helping clinicians better understand the mechanisms of PRP and are guiding novel treatment protocols. In this paper, the value of PRP as a treatment for acute or chronic tendon and muscle disorders is explored.

Types and epidemiology of tendinopathy.

During the last few decades, the role of sports and physical activity has become more and more important in all modern communities. The risk of tendon injury has thus increased, and prevention has become important. Epidemiologic studies are important when planning prevention programs for tendon injuries. Because of individual sport cultures and different sport habits in different countries, national epidemiologic studies are of importance in each individual country.

[Correlations between the ABO blood group system and tendon rupture]. / Az ABO vércsoport-rendszer és az inruptura kapcsolata.

53 per cent of the 873 cases of subcutaneous (spontaneous) tendon ruptures, treated in the National Institute of Traumatology belonged to the blood group O, and that was significantly higher than in the healthy population (31.1 per cent) of Hungary. The ratio of the tendon rupture patients belonging to the blood group A was significantly lower (27.1 per cent) than in the population (42,4 per cent). The ratio of the cases belonging to the blood group O among the multiple tendon rupture and rerupture patients proved to be over 70 per cent. On the basis of their data authors think that there is a relation between the ABO blood group system and the tendon rupture: those belonging to the blood group O are more endangered by, those belonging to the blood group A are more protected against tendon rupture. No relation was found between the Rh(D) blood group system and the tendon rupture.