Cyclic mechanical stretching induces autophagic cell death in tenofibroblasts through activation of prostaglandin E2 production.

BACKGROUND/AIMS: Autophagic cell death has recently been implicated in the pathophysiology of tendinopathy. Prostaglandin E2 (PGE2), a known inflammatory mediator of tendinitis, inhibits tenofibroblast proliferation in vitro; however, the underlying mechanism is unclear. The present study investigated the relationship between PGE2 production and autophagic cell death in mechanically loaded human patellar tendon fibroblasts (HPTFs) in vitro. METHODS: Cultured HPTFs were subjected to exogenous PGE2 treatment or repetitive cyclic mechanical stretching. Cell death was determined by flow cytometry with acridine orange/ethidium bromide staining. Induction of autophagy was assessed by autophagy markers including the formation of autophagosomes and autolysosomes (by electron microscopy, AO staining, and formation of GPF-LC3-labeled vacuoles) and the expression of LC3-II and BECN1 (by western blot). Stretching-induced PGE2 release was determined by ELISA. RESULTS: Exogenous PGE2 significantly induced cell death and autophagy in HPTFs in a dose-dependent manner. Blocking autophagy using inhibitors 3-methyladenine and chloroquine, or small interfering RNAs against autophagy genes Becn-1 and Atg-5 prevented PGE2-induced cell death. Cyclic mechanical stretching at 8% and 12% magnitudes for 24 h significantly stimulated PGE2 release by HPTFs in a magnitude-dependent manner. In addition, mechanical stretching induced autophagy and cell death. Blocking PGE2 production using COX inhibitors indomethacin and celecoxib significantly reduced stretching-induced autophagy and cell death. CONCLUSION: Taken together, cyclic mechanical stretching induces autophagic cell death in tenofibroblasts through activation of PGE2 production.

Sclerosing injections and ultrasound-guided arthroscopic shaving for patellar tendinopathy: good clinical results and decreased tendon thickness after surgery-a medium-term follow-up study.

PURPOSE: Treatment of patellar tendinopathy/jumper's knee with ultrasound-guided sclerosing injections or ultrasound-guided arthroscopic shaving has shown good clinical short-term results. Former studies indicate that the tendon thickness and structure stays unaffected after successful treatment. The aim of this study was to evaluate the sonographic findings and clinical outcome 3-5 years after treatment of patellar tendinopathy with ultrasound-guided sclerosing injections or arthroscopic shaving. METHODS: Fifty-seven patellar tendons (43 patients) with chronic patellar tendinopathy were evaluated, with ultrasound, colour Doppler (CD) and visual analogue scale (VAS) for pain and satisfaction with treatment, 3-5 years after treatment. Functional status was evaluated with a single question-"Back in full loading activity?" yes or no. RESULTS: At endpoint (mean 46 months), there was a significant decrease in anteroposterior thickness of the proximal patellar tendon in patients treated with ultrasound-guided arthroscopic shaving but not after sclerosing injections. Tendon structure had improved, and CD local blood flow had diminished significantly in both groups. There were good clinical results with a significant decrease in VAS for pain after sclerosing injections (VAS 64 ± 18 â†’ 17 ± 23) with 74 % satisfied patients and also after arthroscopic shaving (VAS 77 ± 16 â†’ 13 ± 23) with 80 % satisfied patients. There were no significant differences in VAS between groups. A significant correlation between low local blood flow and high patient satisfaction was found. CONCLUSIONS: Tendon thickness decreased over time after ultrasound-guided arthroscopic shaving, and tendon structure and local blood flow decreased after both treatments. There were good, and similar, clinical results with both methods. LEVEL OF EVIDENCE: III.

Differences in anterior cruciate ligament elasticity and force for knee flexion in women: oral contraceptive users versus non-oral contraceptive users.

Eighty-two percent of sexually active women aged 15-44 have used oral contraceptive pills (OCP) in the United States. The OCP, an exogenous source of synthetic forms of steroid hormones, prevents ovulation. Hormone changes during the menstrual cycle (MC) are believed to have an impact on anterior cruciate ligament (ACL) laxity due to estrogen. Because the estrogen receptor ß resides on human connective tissue, OCP may have potential impact on tendon and ligament synthesis, structure, and biomechanical properties. Temperature has also been known to have an effect on tissue elasticity. Therefore, the purpose of this study was to investigate the differences in ACL elasticity, force to flex the knee (FFK), and knee flexion-extension hysteresis (KFEH) between OCP users and non-OCP users. To investigate these changes, two different knee temperatures were measured. Nineteen young females were divided into two groups: OCP users and non-OCP users. Blood for estradiol serum concentration (E2) was taken before beginning the tests. ACL elasticity, FFK, and KFEH were assessed both at ambient temperature (22 °C) and after 38 °C warming of the leg to stabilize tissue temperature. Assessments were performed four times during the MC. Throughout the MC, ACL elasticity, FFK, and KFEH fluctuated in non-OCP users, but not in OCP users. At ambient temperature, ACL elasticity was significantly lower and FFK and KFEH were significantly higher in OCP users than non-OCP users (p < 0.05). But, no significant differences in FFK and KFEH between the two groups were found after warming to 38 °C.

Local administration of insulin-like growth factor-I (IGF-I) stimulates tendon collagen synthesis in humans.

Collagen is the predominant structural protein in tendons and ligaments, and can be controlled by hormonal changes. In animals, injections of insulin-like growth factor I (IGF-I) has been shown to increase collagen synthesis in tendons and ligaments and to improve structural tissue healing, but the effect of local IGF-I administration on tendon collagen synthesis in human has not been studied. The purpose of this study was to study whether local injections of IGF-I would have a stimulating effect on tendon collagen synthesis. Twelve healthy nonsmoking men [age 62 ± 1 years (mean ± SEM), BMI 27 ± 1] participated. Two injections of either human recombinant IGF-I (0.1 mL Increlex©) or saline (control) into each patellar tendon were performed 24-h apart, respectively. Tendon collagen fractional synthesis rate (FSR) was measured by stable isotope technique in the hours after the second injection. Simultaneously, interstitial peritendinous (IGF-I) and [procollagen type I N-terminal propeptide (PINP)], as a marker for type I collagen synthesis, were determined by microdialysis technique. Tendon collagen FSR and PINP were significantly higher in the IGF-I leg compared with the control leg (P < 0.05). In conclusion, local IGF-I administration can directly enhance tendon collagen synthesis both within and around the human tendon tissue.

Differential cross-linking and radio-protective effects of genipin on mature bovine and human patella tendons.

Gamma irradiation is a proven sterilization method, but is not widely used on allografts for anterior cruciate ligament reconstruction (e.g., patella tendon) due to radiation-induced decreases in mechanical strength. Addressing this drawback would improve the safety and supply of allografts to meet current and future demand. It was hypothesized that genipin-induced collagen cross-linking would increase the tensile modulus of patella tendon tissue such that 5 MRad gamma irradiation would not reduce the tissue mechanical strength below the original untreated values. Optimized genipin treatment increased the tensile modulus of bovine tendons by ~2.4-fold. After irradiation, genipin treated tissue did not significantly differ from native tissue, proving the hypothesis. Optimized genipin treatment of human tendons increased the tensile modulus by ~1.3-fold. After irradiation, both control and genipin-treated tissues possessed ~50-60% of their native tendon modulus, disproving the hypothesis. These results highlight possible age- and species- dependent effects of genipin cross-linking on tendon tissue. Cross-linking of human allografts may be beneficial only in younger donor tissues. Future research is warranted to better understand the mechanisms and applications of collagen cross-linking for clinical use.

Chlorhexidine gluconate cleansing has no effect on the structural properties of human patellar tendon allografts.

PURPOSE: If an anterior cruciate ligament graft somehow becomes contaminated intraoperatively, soaking it in 4% chlorhexidine gluconate has been shown to be the most popular and efficacious method for sterilization before implantation. The purpose of this study was to evaluate the effects of a chlorhexidine soak on the structural properties of human patellar tendon allografts. METHODS: Sixteen human patellar tendon allografts were randomly split into 2 groups of 8. Grafts in 1 group were soaked in 4% chlorhexidine gluconate for 30 minutes, and the other grafts were kept moist in normal saline-soaked gauze. Data on preload width, preload thickness, elongation, ultimate tensile load, and stiffness were obtained through measurement and mechanical testing of the grafts. RESULTS: Graft donor ages ranged from 29 to 43 years. There was no difference in the mean values of graft dimensions of the chlorhexidine-exposed group versus the normal saline-exposed group before mechanical testing (width of 9.48 mm v 9.56 mm, P = .89; thickness of 4.01 mm v 4.57 mm, P = .34). Graft elongation was not statistically different between the groups (2.52 mm v 1.43 mm, P = .27). No statistically significant difference was noted between the ultimate tensile load (2,219 N v 1,878 N, P = .36) or stiffness (274.3 N/mm v 297.0 N/mm, P = .63) of the grafts in both groups. CONCLUSIONS: Structural properties of human patellar tendon allografts are not significantly affected by soaking in 4% chlorhexidine gluconate for 30 minutes. CLINICAL RELEVANCE: Surgeons wishing to treat an inadvertently contaminated graft intraoperatively with 4% chlorhexidine may do so without concern that such treatment will impact graft strength.

Tensile properties of human collagen fibrils and fascicles are insensitive to environmental salts.

To carry out realistic in vitro mechanical testing on anatomical tissue, a choice has to be made regarding the buffering environment. Therefore, it is important to understand how the environment may influence the measurement to ensure the highest level of accuracy. The most physiologically relevant loading direction of tendon is along its longitudinal axis. Thus, in this study, we focus on the tensile mechanical properties of two hierarchical levels from human patellar tendon, namely: individual collagen fibrils and fascicles. Investigations on collagen fibrils and fascicles were made at pH 7.4 in solutions of phosphate-buffered saline at three different concentrations as well as two HEPES buffered solutions containing NaCl or NaCl + CaCl2. An atomic force microscope technique was used for tensile testing of individual collagen fibrils. Only a slight increase in relative energy dissipation was observed at the highest phosphate-buffered saline concentration for both the fibrils and fascicles, indicating a stabilizing effect of ionic screening, but changes were much less than reported for radial compression. Due to the small magnitude of the effects, the tensile mechanical properties of collagen fibrils and fascicles from the patellar tendon of mature humans are essentially insensitive to environmental salt concentration and composition at physiological pH.

Fluoroquinolone-associated bilateral patellar tendon rupture: a case report and review of the literature.

Single series case reports have described bilateral traumatic patellar tendon ruptures, and less frequently, with little or no trauma. Patellar tendon rupture most often occurs in patients younger than 40 years old and is commonly precipitated by a sudden, significant eccentric contraction. Patellar tendon ruptures are uncommon in those older than 40 years of age, but when they occur, may indicate an underlying systemic disorder. Corticosteroid injections, rheumatic disease, metabolic disorders, and fluoroquinolone use have all been associated with increased risk of tendon rupture. While the Achilles tendon is the most commonly affected by fluoroquinolone use, cases involving the rotator cuff, biceps, wrist extensors, and quadriceps tendon among others, have been described. A case is presented of a 43-year-old man without pre-existing medical comorbidities who sustained atraumatic bilateral patellar tendon ruptures following a treatment course of fluoroquinolone medication.

Effect of combined administration of transforming growth factor-b1 and insulin-like growth factor I on the mechanical properties of a patellar tendon defect model in rabbits.

The aim of this study was to test the hypothesis that combined administration of TGF-b1 and IGF-I in a patellar tendon defect model could enhance the mechanical properties of the healed tendon. Twenty four New Zealand white rabbits were used for this purpose. In each animal, the right knee was used for the application of the growth factors, whereas the left knee served as an untreated control. The growth factors were mixed with fibrin sealant as a delivery vehicle. Two groups of rabbits were sacrificed after 2 weeks and 6 weeks respectively. Application of the growth factors resulted in a significant increase in force at failure, ultimate stress, stiffness, and energy uptake at 2 weeks, whereas none of the parameters revealed any significant difference between the two groups at 6 weeks. This study provides valuable information on the effect of the two growth factors on this patellar tendon defect model.

Current pharmacological approaches to the treatment of tendinopathy.

INTRODUCTION: Tendinopathies are common in elite and recreational athletes: traditionally considered overuse injuries, they involve excessive tensile loading and subsequent breakdown of the loaded tendon. Many pharmacological treatments have been proposed for the management of tendinopathy, with no agreement regarding the overall best option available both for Achilles and patellar tendinopathy. AREAS COVERED: The present article reports the best scientific evidence regarding the efficacy and safety of different pharmacological treatments in different types of tendinopathy, focusing on Achilles and patellar tendinopathy, the conditions on which more studies have been published. EXPERT OPINION: No univocal evidence exists regarding the best non-operative management, which includes non-steroidal anti-inflammatory drugs, platelet-rich plasma, high volume image-guided injections, hyaluronic acid, and prolotherapy, for tendinopathy (in particular Achilles and patellar tendinopathies) as a suitable alternative to the commonly used eccentric loading rehabilitation regimen. It is unclear whether the combination of pharmacological substances with physical therapy would produce better results than physical therapy alone. There is an overall lack of published well-performed randomized controlled trials comparing the various options available for the management of tendinopathy, studying large cohorts of patients for adequately long follow-up periods and with well-validated standardized scores and scales.

Effect of estrogen on tendon collagen synthesis, tendon structural characteristics, and biomechanical properties in postmenopausal women.

The knowledge about the effect of estradiol on tendon connective tissue is limited. Therefore, we studied the influence of estradiol on tendon synthesis, structure, and biomechanical properties in postmenopausal women. Nonusers (control, n = 10) or habitual users of oral estradiol replacement therapy (ERT, n = 10) were studied at rest and in response to one-legged resistance exercise. Synthesis of tendon collagen was determined by stable isotope incorporation [fractional synthesis rate (FSR)] and microdialysis technique (NH(2)-terminal propeptide of type I collagen synthesis). Tendon area and fibril characteristics were determined by MRI and transmission electron microscopy, whereas tendon biomechanical properties were measured during isometric maximal voluntary contraction by ultrasound recording. Tendon FSR was markedly higher in ERT users (P < 0.001), whereas no group difference was seen in tendon NH(2)-terminal propeptide of type I collagen synthesis (P = 0.32). In ERT users, positive correlations between serum estradiol (s-estradiol) and tendon synthesis were observed, whereas change in tendon synthesis from rest to exercise was negatively correlated to s-estradiol. Tendon area, fibril density, fibril volume fraction, and fibril mean area did not differ between groups. However, the percentage of medium-sized fibrils was higher in ERT users (P < 0.05), whereas the percentage of large fibrils tended to be greater in control (P = 0.10). A lower Young's modulus (GPa/%) was found in ERT users (P < 0.05). In conclusion, estradiol administration was associated with higher tendon FSR and a higher relative number of smaller fibrils. Whereas this indicates stimulated collagen turnover in the resting state, collagen responses to exercise were negatively associated with s-estradiol. These results indicate a pivotal role for estradiol in maintaining homeostasis of female connective tissue.

Glucosamine sulfate effect on the degenerated patellar cartilage: preliminary findings by pharmacokinetic magnetic resonance modeling.

Normal and degenerated cartilages have different magnetic resonance (MR) capillary permeability (K(trans)) and interstitial interchangeable volume (v(e)). Our hypothesis was that glucosamine sulfate treatment modifies these neovascularity abnormalities in osteoarthritis. Sixteen patients with patella degeneration, randomly distributed into glucosamine or control groups, underwent two 1.5-Tesla dynamic contrast-enhanced MR imaging studies (treatment initiation and after 6 months). The pain visual analog scale (VAS) and American Knee Society (AKS) score were used. A two-compartment pharmacokinetic model was used. Percentages of variations (postreatment-pretreatment/pretreatment) were compared (t-test for independent data). In the glucosamine group, pain and functional outcomes statistically improved (VAS: 7.3 +/- 1.1 to 3.6 +/- 1.3, p < 0.001; AKS: 18.6 +/- 6.9 to 42.9 +/- 2.7, p < 0.01). Glucosamine significantly increased K(trans) at 6 months (-54.4 +/- 21.2% vs 126.7 +/- 56.9%, p < 0.001, control vs glucosamine). In conclusion, glucosamine sulfate decreases pain while improving functional outcome in patients with cartilage degeneration. Glucosamine sulfate increases K(trans), allowing its proposal as a surrogate imaging biomarker after 6 months of treatment.

The effect of platelet-rich plasma gel in the early phase of patellar tendon healing.

INTRODUCTION: The aim of this study is to assess if an application of platelet-rich plasma (PRP) gel would improve the mechanical properties of rabbit's patellar tendon after resecting its central portion. MATERIALS AND METHODS: Forty skeletally mature New Zealand White rabbits were used. Two groups ten rabbits each (PRP and control group) were used to evaluate mechanical properties and histology after 14 days and two groups ten rabbits each (PRP and control groups) were used to evaluate mechanical properties and histology after 28 days. RESULTS: At 14 days, PRP group showed a 72.2% increase in force at failure, a 39.1% increase in ultimate stress, and a 53.1% increase in stiffness, as compared with controls. These changes were statistically significant (P < 0.05). At 28 days, there was no longer any significant difference between PRP and control groups (P > 0.05). DISCUSSION: In our study, the mechanical properties of the regenerated tendon in the PRP group were significantly improved in relation to the control group. It appears that PRP has a strong effect in the early phase of tendon healing. This effect is probably due to the growth factors that are released from the platelets during activation.

In vitro reversal of the load-bearing properties of lipid-depleted articular cartilage following exposure to phospholipid surfactant solutions.

BACKGROUND: A microscopic layer of surface active phospholipids overlays the articular cartilage of the knee. Its depletion in osteoarthritic joints results in loss of lubrication and load-bearing efficiency. We hypothesize that exposure of articular cartilage to the dominant unsaturated phospholipid component of knee surfactant can regenerate the load-bearing properties of the tissue. This was evaluated by studying the stress-strain and stiffness characteristics of normal intact and lipid-depleted cartilage exposed to lipid-based surfactants for known durations. METHODS: Normal intact, lipid-depleted and surfactant-treated bovine articular cartilage specimens were compressed at 0.5mm/min to a maximum strain of 40% and their stress-strain and stiffness data were compared. FINDINGS: The stiffness of lipid-depleted samples increased by 40% on average relative to the normal; after exposure of the same samples to saturated surfactant for one and 24h, the average stiffness decreased by 25% and 62%, respectively from this high value. On the other hand, exposure of delipidized specimens to a mixture of selected unsaturated surfactant species for one and 24h resulted in a reduction of 85% and 90% in the stiffness of the depilidized samples respectively, largely reversing the effect of lipid removal to a level much closer to that of the normal intact cartilage and therefore better than that obtained with incubation in the saturated surfactant. INTERPRETATION: Lipid loss in articular cartilage results in a consistent increase in stiffness relative to normal tissue stiffness. This consequence of lipid loss can be partially reversed by the reintroduction of surface active phospholipids. The results of this study show that the lipid components of cartilage play an important role in determining the compliance of the loaded tissue.

Dual growth factor-immobilized asymmetrically porous membrane for bone-to-tendon interface regeneration on rat patellar tendon avulsion model.

Insufficient repair of the bone-to-tendon interface (BTI) with structural/compositional gradients has been a significant challenge in orthopedics. In this study, dual growth factor (platelet-derived growth factor-BB [PDGF-BB] and bone morphogenetic protein-2 [BMP-2])-immobilized polycaprolactone (PCL)/Pluronic F127 asymmetrically porous membrane was fabricated to estimate its feasibility as a potential strategy for effective regeneration of BTI injury. The growth factors immobilized (via heparin-intermediated interactions) on the membrane were continuously released for up to ∼80% of the initial loading amount after 5 weeks without a significant initial burst. From the in vivo animal study using a rat patellar tendon avulsion model, it was observed that the PDGF-BB/BMP-2-immobilized membrane accelerates the regeneration of the BTI injury, probably because of the continuous release of both growth factors (biological stimuli) and their complementary effect to create a multiphasic structure (bone, fibrocartilage, and tendon) like a native structure, as well as the role of the asymmetrically porous membrane as a physical barrier (nanopore side; prevention of fibrous tissue invasion into the defect site) and scaffold (micropore side; guidance for tissue regeneration). © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 115-125, 2018.

Calcific tendonitis : a model.

Calcific tendonitis is a common clinical condition associated with high rates of tendon rupture, prolonged symptoms, and poor response to therapy. Little is known about the pathogenesis of calcifications in tendons and consequently few effective therapies are available. We hypothesized that tendon calcification, like pathologic calcification in other sites, was generated by extracellular organelles known as matrix vesicles and that isolated matrix vesicles would constitute the basis for a useful model of this process. Tendon matrix vesicles were isolated from adult porcine patellar tendons using enzymatic digestion and differential centrifugation. Vesicle morphology was examined with electron microscopy. Levels of calcium, phosphate, pyrophosphate, ATP, and mineralization-associated enzymes were measured and compared with articular cartilage vesicles from porcine articular cartilage. Vesicles were embedded in agarose gels with or without type I collagen or dermatan sulfate and incubated in calcifying salt solution trace labeled with (45)calcium. (45)Calcium in the vesicle fraction was measured after 5-7 days. The type of mineral formed was determined by micro-x-ray diffraction. Matrix vesicles isolated from adult porcine tendon were similar morphologically to those obtained from articular cartilage. They contained mineralization-related enzymes and formed hydroxyapatite mineral in vitro. Mineralization was suppressed by levamisole and modulated by extracellular matrix components. Matrix vesicles isolated from tendons mineralize in vitro. This model may aid in the study of the pathogenesis of calcific tendonitis as well as serve as a means to identify effective therapies for this common disorder.

Contrast enhanced cartilage imaging: Comparison of ionic and non-ionic contrast agents.

Our objective was to compare relaxation effects, dynamics and spatial distributions of ionic and non-ionic contrast agents in articular cartilage at concentrations typically used for direct MR arthrography at 1.5T. Dynamic MR-studies over 11h were performed in 15 bovine patella specimens. For each of the contrast agents gadopentetate dimeglumine, gadobenate dimeglumine, gadoteridol and mangafodipir trinatrium three patellae were placed in 2.5mmol/L contrast solution. Simultaneous measurements of T(1) and T(2) were performed every 30min using a high-spatial-resolution "MIX"-sequence. T(1), T(2) and DeltaR(1), DeltaR(2) profile plots across cartilage thickness were calculated to demonstrate the spatial and temporal distributions. The charge is one of the main factors which controls the amount of the contrast media diffusing into intact cartilage, but independent of the charge, the spatial distribution across cartilage thickness remains highly inhomogeneous even after 11h of diffusion. The absolute DeltaR(2)-effect in cartilage is at least as large as the DeltaR(1)-effect for all contrast agents. Maximum changes were 5-12s(-1) for DeltaR(1) and 8-15s(-1) for DeltaR(2). This study indicates that for morphologically intact cartilage only the amount of contrast agents within cartilage is determined by the charge but not the spatial distribution across cartilage thickness. In addition, DeltaR(2) can be considered for quantification of contrast agent concentrations, since it is of the same magnitude and less time consuming to measure than DeltaR(1).

The responses of extrinsic fibroblasts infiltrating the devitalised patellar tendon to IL-1beta are different from those of normal tendon fibroblasts.

In order to clarify the role of cytokines in the remodelling of the grafted tendon for ligament reconstruction we compared the responses to interleukin (IL)-1beta, platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-beta1 of extrinsic fibroblasts infiltrating the frozen-thawed patellar tendon in rats with that of the normal tendon fibroblasts, in regard to the gene expression of matrix metalloproteinase (MMP)-13, using Northern blot analysis. We also examined, immunohistologically, the local expression of IL-1beta, PDGF-BB, and TGF-beta1 in fibroblasts infiltrating the frozen-thawed patellar tendon. Northern blot analysis showed that fibroblasts derived from the patellar tendon six weeks after the freeze-thaw procedure in situ showed less response to IL-1beta than normal tendon fibroblasts with respect to MMP-13 mRNA gene expression. The immunohistological findings revealed that IL-1beta was over-expressed in extrinsic fibroblasts which infiltrated the patellar tendon two and six weeks after the freeze-thaw procedure in situ, but neither PDGF-BB nor TGF-beta1 was over-expressed in these extrinsic fibroblasts. Our findings indicated that IL-1beta had a close relationship to matrix remodelling of the grafted tendon for ligament reconstruction, in addition to the commencement of inflammation during the tissue-healing process.

Proanthocyanidins Attenuation of H2O2-Induced Oxidative Damage in Tendon-Derived Stem Cells via Upregulating Nrf-2 Signaling Pathway.

Proanthocyanidins (PCs) have shown inhibition of oxidative damage by improving Nrf-2 expression in many tissues. However, the cytoprotective effects of PCs on H2O2-induced tendon damage have not been verified. The current study was aimed at assessing the cytoprotection of PCs on the oxidative cellular toxicity of tendon-derived stem cells (TDSCs) induced by H2O2. The TDSCs were isolated from patellar tendons of Sprague Dawley (SD) rats, and the cells after third passage were used for subsequent experiments. The isolated cells were identified by flow cytometry assay and multidifferentiation potential assay. Cell Counting Kit-8 assay was performed to examine cell viability. Real-Time PCR and Western Blot were employed to, respectively, assess the mRNA and protein expressions of Nrf-2, GCLM, NQO-1, and HO-1. PCs significantly improved the cell viability of TDSCs. Furthermore, H2O2 upregulated Nrf-2, GCLM, NQO-1, and HO-1 without significant difference, while the proteins expressions were increased with significant difference in PCs group and PCs + H2O2 cotreated group. All the findings indicated that PCs could protect against the oxidative damage induced by H2O2 in TDSCs, and the cytoprotective effects might be due to the ability of PCs to activate the expressions of GCLM, HO-1, and NQO-1 via upregulating Nrf-2 signaling pathway.

Peritendinous injection of platelet-rich plasma to treat tendinopathy: A retrospective review.

OBJECTIVE: The aim of this study was to determine factors associated with the likelihood of a better clinical outcome after the peritendinous injection of PRP for the treatment of chronic tendinopathy and identify whether PRP represents an effective treatment option for chronic tendinopathies. METHODS: The study included 214 patients (86 males and 128 females; mean age: 39.3 (18-75) years) who received PRP injections for tendinopathy refractory to conventional treatments. The mean duration of symptoms at the moment of the PRP treatment was 8.3 months. Primary outcome measurement was perceived improvement in symptoms for each anatomic compartment for upper and lower limbs at 6 months after treatment. Also, a visual analog scale (VAS) score (pain intensity on a 0-10 scale) was used for pain scoring questionnaire before treatment, 6 weeks and 6 months following the PRP injection(s). To identify factors associated with the likelihood of a better clinical outcome, patients were categorized on the basis of their perceived improvement in symptoms 6 months after the PRP injection(s)-that is, as lower (less than 50% global improvement) or higher (more than 50% global improvement). RESULTS: A visual analogue scale score and perceived improvement in symptoms were significantly lower after peritendinous injection in 6-week and 6-month follow-ups compared with the baseline (P < 0.001) except for peroneal and Achilles tendons. Overall, 83% of patients indicated moderate to complete improvement in symptoms. The most common injection sites were the lateral epicondyle, Achilles, and patellar tendons. Furthermore, 30% of patients received only 1 injection, 30% received 2 injections, and 40% received 3 or more injections. A total of 85% of patients were satisfied (more than 50% global improvement) with the procedure. In addition, upper limb tendons, increase in the age, and female gender were associated with a higher likelihood of perceived improvement in symptoms. CONCLUSIONS: In the present retrospective study assessing PRP injections in the treatment of chronic tendinopathy, a moderate improvement (>50%) in pain symptoms was observed in most of the patients. Our research found that results were most promising with patellar and lateral epicondylar tendinopathy in the short to medium term. Female patients, patients with upper extremity tendinopathy and older patients appeared to benefit more from PRP injection. LEVEL OF EVIDENCE: Level IV, Therapeutic study.