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1.
J Cell Mol Med ; 28(13): e18508, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38953556

RESUMEN

Both osteoporosis and tendinopathy are widely prevalent disorders, encountered in diverse medical contexts. Whilst each condition has distinct pathophysiological characteristics, they share several risk factors and underlying causes. Notably, oxidative stress emerges as a crucial intersecting factor, playing a pivotal role in the onset and progression of both diseases. This imbalance arises from a dysregulation in generating and neutralising reactive oxygen species (ROS), leading to an abnormal oxidative environment. Elevated levels of ROS can induce multiple cellular disruptions, such as cytotoxicity, apoptosis activation and reduced cell function, contributing to tissue deterioration and weakening the structural integrity of bones and tendons. Antioxidants are substances that can prevent or slow down the oxidation process, including Vitamin C, melatonin, resveratrol, anthocyanins and so on, demonstrating potential in treating these overlapping disorders. This comprehensive review aims to elucidate the complex role of oxidative stress within the interlinked pathways of these comorbid conditions. By integrating contemporary research and empirical findings, our objective is to outline new conceptual models and innovative treatment strategies for effectively managing these prevalent diseases. This review underscores the importance of further in-depth research to validate the efficacy of antioxidants and traditional Chinese medicine in treatment plans, as well as to explore targeted interventions focused on oxidative stress as promising areas for future medical advancements.


Asunto(s)
Antioxidantes , Osteoporosis , Estrés Oxidativo , Especies Reactivas de Oxígeno , Tendinopatía , Humanos , Osteoporosis/metabolismo , Osteoporosis/terapia , Osteoporosis/tratamiento farmacológico , Antioxidantes/uso terapéutico , Tendinopatía/metabolismo , Tendinopatía/terapia , Tendinopatía/patología , Especies Reactivas de Oxígeno/metabolismo , Animales
2.
Int J Mol Sci ; 25(13)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-39000426

RESUMEN

Achilles tendinopathy (TP) is characterized as the third most common disease of the musculoskeletal system, and occurs in three phases. There is currently no evidence of effective treatment for this medical condition. In this study, the modulatory effects of the minimally invasive technique intratissue percutaneous electrolysis (EPI) and combinations of EPI with four nutritional factors included in the diet, hydroxytyrosol (HT), maslinic acid (MA), glycine, and aspartate (AA), on hepatic intermediary metabolism was examined in Wistar rats with induced tendinopathy at various stages of TP. Results obtained showed that induced tendinopathy produced alterations in the liver intermediary metabolisms of the rats. Regarding carbohydrate metabolism, a reduction in the activity of pro-inflammatory enzymes in the later stages of TP was observed following treatment with EPI alone. Among the combined treatments using nutritional factors with EPI, HT+EPI and AA+EPI had the greatest effect on reducing inflammation in the late stages of TP. In terms of lipid metabolism, the HT+EPI and AA+EPI groups showed a decrease in lipogenesis. In protein metabolism, the HT+EPI group more effectively reduced the inflammatory effects of induced TP. Treatment with EPI combined with nutritional factors might help regulate intermediary metabolism in TP disease and reduce the inflammation process.


Asunto(s)
Electrólisis , Hígado , Ratas Wistar , Tendinopatía , Animales , Electrólisis/métodos , Ratas , Tendinopatía/metabolismo , Tendinopatía/terapia , Tendinopatía/etiología , Tendinopatía/patología , Hígado/metabolismo , Hígado/patología , Masculino , Metabolismo de los Lípidos , Tendón Calcáneo/metabolismo , Tendón Calcáneo/patología , Modelos Animales de Enfermedad
3.
Sci Rep ; 14(1): 13540, 2024 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-38866832

RESUMEN

Mast cells are immune cells minimally present in normal tendon tissue. The increased abundance of mast cells in tendinopathy biopsies and at the sites of tendon injury suggests an unexplored role of this cell population in overuse tendon injuries. Mast cells are particularly present in tendon biopsies from patients with more chronic symptom duration and a history of intensive mechanical loading. This study, therefore, examined the cross talk between mast cells and human tendon cells in either static or mechanically active conditions in order to explore the potential mechanistic roles of mast cells in overuse tendon injuries. A coculture of isolated human tenocytes and mast cells (HMC-1) combined with Flexcell Tension System for cyclic stretching of tenocytes was used. Additionally, human tenocytes were exposed to agonists and antagonists of substance P (SP) receptors. Mast cell degranulation was assessed by measuring ß-hexosaminidase activity. Transwell and cell adhesion assays were used to evaluate mast cell migration and binding to tendon extracellular matrix components (collagen and fibronectin), respectively. Gene expressions were analyzed using real time qRT-PCR. Our results indicate that mechanical stimulation of human tenocytes leads to release of SP which, in turn, activates mast cells through the Mas-related G-protein-coupled receptor X2 (MRGPRX2). The degranulation and migration of mast cells in response to MRGPRX2 activation subsequently cause human tenocytes to increase their expression of inflammatory factors, matrix proteins and matrix metalloproteinase enzymes. These observations may be important in understanding the mechanisms by which tendons become tendinopathic in response to repetitive mechanical stimulation.


Asunto(s)
Mastocitos , Receptores Acoplados a Proteínas G , Receptores de Neuropéptido , Sustancia P , Tendones , Tenocitos , Humanos , Sustancia P/metabolismo , Sustancia P/farmacología , Mastocitos/metabolismo , Tenocitos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropéptido/metabolismo , Receptores de Neuropéptido/genética , Tendones/metabolismo , Tendones/patología , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Degranulación de la Célula , Tendinopatía/metabolismo , Tendinopatía/patología , Inflamación/metabolismo , Inflamación/patología , Masculino , Técnicas de Cocultivo , Células Cultivadas , Adulto , Movimiento Celular
4.
Sports Med Arthrosc Rev ; 32(1): 12-16, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38695498

RESUMEN

Rotator cuff repair is usually successful, but retear is not uncommon. It has been previously identified that there is a higher incidence of apoptosis in the edges of the torn supraspinatus tendon. A prospective cohort study was conducted with 28 patients-14 rotator cuff tear patients, 5 instability patients, and 9 Anterior cruciate ligament reconstruction patients to determine whether there was any increase in several genes implicated in apoptosis, including Fas receptor (FasR), Fas ligand, Aifm-1, Bcl-2, Fadd, Bax, and caspase-3. There was a significant expression of Bax (P=0.2) and FasR (P=0.005) in the edges of torn supraspinatus tendons, and in intact subscapularis tendons, there was a significant expression of caspase-3 (P=0.02) compared with samples from the torn supraspinatus tendon (P=0.04). The cytochrome c pathway, with its subsequent activation of caspase-3, as well as the TRAIL-receptor signaling pathway involving FasR have both been implicated. The elevated expression of Bax supported the model that the Bax to Bcl-2 expression ratio represents a cell death switch. The elevated expression of Bax in the intact subscapularis tissue from rotator cuff tear patients also may confirm that tendinopathy is an ongoing molecular process.


Asunto(s)
Apoptosis , Lesiones del Manguito de los Rotadores , Tendinopatía , Humanos , Lesiones del Manguito de los Rotadores/metabolismo , Lesiones del Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/patología , Tendinopatía/patología , Tendinopatía/metabolismo , Estudios Prospectivos , Masculino , Proteína X Asociada a bcl-2/metabolismo , Femenino , Receptor fas/metabolismo , Caspasa 3/metabolismo , Manguito de los Rotadores/patología , Manguito de los Rotadores/metabolismo , Persona de Mediana Edad , Transducción de Señal , Adulto
5.
Int J Mol Sci ; 25(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38731971

RESUMEN

Tendinopathy, characterized by inflammatory and degenerative changes, presents challenges in sports and medicine. In addressing the limitations of conservative management, this study focuses on developing tendon grafts using extrusion bioprinting with platelet-rich plasma (PRP)-infused hydrogels loaded with tendon cells. The objective is to understand paracrine interactions initiated by bioprinted tendon grafts in either inflamed or non-inflamed host tissues. PRP was utilized to functionalize methacrylate gelatin (GelMA), incorporating tendon cells for graft bioprinting. Bioinformatic analyses of overexpressed proteins, predictive of functional enrichment, revealed insights into PRP graft behavior in both non-inflamed and inflamed environments. PRP grafts activated inflammatory pathways, including Interleukin 17 (IL-17), neuroinflammation, Interleukin 33 (IL-33), and chemokine signaling. Interleukin 1 beta (IL-1b) in the graft environment triggered p38 mitogen-activated protein kinase (MAPK) signaling, nuclear factor kappa light chain enhancer of activated B cells (NF-kB) canonical pathway, and Vascular Endothelial Growth Factor (VEGF) signaling. Biological enrichment attributed to PRP grafts included cell chemotaxis, collagen turnover, cell migration, and angiogenesis. Acellular PRP grafts differed from nude grafts in promoting vessel length, vessel area, and junction density. Angiogenesis in cellular grafts was enhanced with newly synthesized Interleukin 8 (IL-8) in cooperation with IL-1b. In conclusion, paracrine signaling from PRP grafts, mediated by chemokine activities, influences cell migration, inflammation, and angiogenic status in host tissues. Under inflammatory conditions, newly synthesized IL-8 regulates vascularization in collaboration with PRP.


Asunto(s)
Bioimpresión , Plasma Rico en Plaquetas , Tendones , Tendones/metabolismo , Bioimpresión/métodos , Animales , Plasma Rico en Plaquetas/metabolismo , Humanos , Ingeniería de Tejidos/métodos , Hidrogeles/química , Andamios del Tejido/química , Tendinopatía/metabolismo , Tendinopatía/terapia , Tendinopatía/patología
6.
Scand J Med Sci Sports ; 34(5): e14665, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38773808

RESUMEN

The objective of the study was to obtain adjusted ultrasonographic reference values of the Achilles tendon thickness (maximum anterior-posterior distance) in adults without (previous) Achilles tendinopathy (AT) and to compare these reference values with AT patients. Six hundred participants were consecutively included, comprising 500 asymptomatic individuals and 100 patients with clinically diagnosed chronic AT. The maximum tendon thickness was assessed using Ultrasound Tissue Characterization. A multiple quantile regression model was developed, incorporating covariates (personal characteristics) that were found to have a significant impact on the maximum anterior-posterior distance of the Achilles tendon. A 95% reference interval (RI) was derived (50th, 2.5th-97.5th percentile). In asymptomatic participants median (95% RI) tendon thickness was 4.9 (3.8-6.9) mm for the midportion region and 3.7 (2.8-4.8) mm for the insertional region. Age, height, body mass index, and sex had a significant correlation with maximum tendon thickness. Median tendon thickness for the midportion region was calculated with the normative equation -2.1 + AGE × 0.021 + HEIGHT × 0.032+ BMI × 0.028 + SEX × 0.05. For the insertional region, the normative equation was -0.34 + AGE × 0.010+ HEIGHT × 0.018 + BMI × 0.022 + SEX × -0.05. In the equations, SEX is defined as 0 for males and 1 for females. Mean (95% CI) difference in tendon thickness compared to AT patients was 2.7 mm (2.3-3.2, p < 0.001) for the midportion and 1.4 mm (1.1-1.7, p < 0.001) for the insertional region. Compared to the asymptomatic population 73/100 (73%) AT patients exhibited increased tendon thickening, with values exceeding the 95% RI. This study presents novel reference values for the thickness of midportion and insertional region of the Achilles tendon, which were adjusted for personal characteristics. Our novel web-based openly accessible calculator for determining normative Achilles tendon thickness (www.achillestendontool.com) will be a useful resource in the diagnostic process. Trial registration number: This trial is registered in the Netherlands Trial Register (NL9010).


Asunto(s)
Tendón Calcáneo , Tendinopatía , Ultrasonografía , Humanos , Tendón Calcáneo/diagnóstico por imagen , Tendón Calcáneo/anatomía & histología , Tendón Calcáneo/patología , Masculino , Femenino , Tendinopatía/diagnóstico por imagen , Tendinopatía/patología , Estudios Transversales , Adulto , Persona de Mediana Edad , Valores de Referencia , Anciano , Índice de Masa Corporal , Adulto Joven , Factores Sexuales
7.
Sci Rep ; 14(1): 11421, 2024 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-38763976

RESUMEN

Achilles tendinopathy is a disabling condition that affects more than 50% of runners. Pre-clinical studies in a large animal model of naturally-occurring tendinopathy similar to human Achilles tendinopathy has shown benefits of autologous bone marrow-derived mesenchymal stem cell (MSC) implantation. However, MSCs are advanced therapies medicinal products (ATMPs), with strict regulatory requirements. Guided by the regulator we carried out a first in man study to assess the safety and efficacy of autologous MSC injection in human patients with non-insertional Achilles tendinopathy. Ten patients, mean age 47 with mid-portion Achilles tendon pain and swelling for more than 6 months, underwent autologous cultured cell injections (median 12.2 × 106, range 5-19 × 106 cells) into their Achilles tendon. At 24 weeks follow-up, no serious adverse reactions or important medical events were observed. MOXFQ, EQ-5D-5L, and VISA-A scores improved clinically at 12 and 24 weeks. VAS pain improved increasingly at 6, 12 and 24 weeks. MOXFQ Pain and VISA-A Scores improved > 12 points from baseline to 24 weeks in 8 patients. Maximum anteroposterior tendon thickness as measured by greyscale US decreased by mean 0.8 mm at 24 weeks. This phase IIa study demonstrated the safety of autologous MSC injection for non-insertional Achilles tendinopathy and provides proof-of-concept of the technique in patients, all of whom had previously failed conservative treatments for chronic disease and leads the way for a larger randomised controlled trial.


Asunto(s)
Tendón Calcáneo , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Tendinopatía , Trasplante Autólogo , Humanos , Tendinopatía/terapia , Tendinopatía/patología , Tendón Calcáneo/patología , Masculino , Trasplante de Células Madre Mesenquimatosas/métodos , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Persona de Mediana Edad , Femenino , Adulto , Células Madre Mesenquimatosas/citología , Resultado del Tratamiento
8.
ACS Biomater Sci Eng ; 10(5): 3293-3305, 2024 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-38666422

RESUMEN

Current in vitro models poorly represent the healthy or diseased tendon microenvironment, limiting the translation of the findings to clinics. The present work aims to establish a physiologically relevant in vitro tendon platform that mimics biophysical aspects of a healthy and tendinopathic tendon matrix using a decellularized bovine tendon and to characterize tendon cells cultured using this platform. Bovine tendons were subjected to various decellularization techniques, with the efficacy of decellularization determined histologically. The biomechanical and architectural properties of the decellularized tendons were characterized using an atomic force microscope. Tendinopathy-mimicking matrices were prepared by treating the decellularized tendons with collagenase for 3 h or collagenase-chondroitinase (CC) for 1 h. The tendon tissue collected from healthy and tendinopathic patients was characterized using an atomic force microscope and compared to that of decellularized matrices. Healthy human tendon-derived cells (hTDCs) from the hamstring tendon were cultured on the decellularized matrices for 24 or 48 h, with cell morphology characterized using f-actin staining and gene expression characterized using real-time PCR. Tendon matrices prepared by freeze-thawing and 48 h nuclease treatment were fully decellularized, and the aligned structure and tendon stiffness (1.46 MPa) were maintained. Collagenase treatment prepared matrices with a disorganized architecture and reduced stiffness (0.75 MPa), mimicking chronic tendinopathy. Treatment with CC prepared matrices with a disorganized architecture without altering stiffness, mimicking early tendinopathy (1.52 MPa). hTDCs on a healthy tendon matrix were elongated, and the scleraxis (SCX) expression was maintained. On tendinopathic matrices, hTDCs had altered morphological characteristics and lower SCX expression. The expression of genes related to actin polymerization, matrix degradation and remodeling, and immune cell invasion were higher in hTDCs on tendinopathic matrices. Overall, the present study developed a physiological in vitro system to mimic healthy tendons and early and late tendinopathy, and it can be used to better understand tendon cell characteristics in healthy and diseased states.


Asunto(s)
Tendinopatía , Tendones , Humanos , Tendones/citología , Animales , Tendinopatía/patología , Tendinopatía/terapia , Bovinos , Matriz Extracelular/metabolismo , Células Cultivadas
9.
Tissue Cell ; 88: 102392, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38643674

RESUMEN

The effect of interleukin-38 (IL-38), a recently identified member of the IL-1 family with potential applications in various inflammation-related conditions, on ER stress has not been explored. Furthermore, its role in obesity-associated tendinopathy has not been investigated. In this study, human primary tenocytes were treated with palmitate (200 or 400 µM) and palmitate plus IL-38 (0-50 ng/mL) for 24 h. Western blotting was used to assess ER stress and tendinopathogenic markers in tenocytes. Monodansylcadaverine (MDC) staining was used to evaluate autophagosomes. Apoptosis was determined by cell viability assays, caspase 3 activity assays and TUNEL assays. Cell migration was evaluated by a cell scratch assay. Small interfering (si) RNA transfection was used for target gene silencing. Treatment of tenocytes with IL-38 attenuated apoptosis, restored the balance between MMPs and TIMP-1, and alleviated ER stress under palmitate conditions. IL-38 treatment enhanced AMPK phosphorylation and promoted the expression of autophagy markers related to LC3 conversion, p62 degradation, and autophagosome formation in cultured tenocytes. The effects of IL-38 on ER stress, apoptosis, and MMP-9, MMP-13, and TIMP-1 expression in palmitate-treated tenocytes were abrogated by AMPK siRNA or 3-methyladenine (3MA). These results suggest that IL-38 alleviates ER stress through the AMPK/autophagy pathway, thereby reducing apoptosis and preventing extracellular matrix (ECM) degradation in tenocytes under hyperlipidemic conditions. This study provides a promising therapeutic avenue for treating obesity-related tendinopathy using an endogenous compound such as IL-38.


Asunto(s)
Apoptosis , Autofagia , Estrés del Retículo Endoplásmico , Obesidad , Tendinopatía , Tenocitos , Humanos , Autofagia/efectos de los fármacos , Tendinopatía/patología , Tendinopatía/metabolismo , Tendinopatía/tratamiento farmacológico , Obesidad/metabolismo , Obesidad/patología , Apoptosis/efectos de los fármacos , Tenocitos/metabolismo , Tenocitos/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Interleucinas/metabolismo , Movimiento Celular/efectos de los fármacos
10.
Vet Res Commun ; 48(3): 1533-1543, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38381244

RESUMEN

Tendon calcification is a commonly associated with degenerative tendinopathy of the Achilles tendons in dogs. It is characterised by the formation of calcific deposits and is refractory to treatment, often re-forming after surgical removal. Little is known about its pathogenesis and therefore the aims of this study were to develop an in vitro model of canine tendon calcification and use this model to investigate mechanisms driving calcification. Cells from the canine Achilles tendon were cultured with different calcifying media to establish which conditions were best able to induce specific, cell-mediated calcification. Once optimum calcification conditions had been established, the effect of ATP treatment on calcification was assessed. Results revealed that 2 mM di-sodium phosphate combined with 2 mM calcium chloride provided the optimum calcifying conditions, increasing calcium deposition and expression of osteogenic-related genes similar to those observed in tendon calcification in vivo. ATP treatment inhibited calcification in a dose-dependent manner, reducing calcium deposition and increasing cell viability, while osteogenic-related genes were no longer upregulated. In conclusion, the in vitro model of canine tendon calcification developed in this study provides the ability to study mechanisms driving tendon calcification, demonstrating that ATP plays a role in modulating tendon calcification that should be explored further in future studies.


Asunto(s)
Tendón Calcáneo , Adenosina Trifosfato , Calcinosis , Animales , Perros , Adenosina Trifosfato/metabolismo , Calcinosis/veterinaria , Calcinosis/patología , Tendón Calcáneo/patología , Tendón Calcáneo/efectos de los fármacos , Enfermedades de los Perros/patología , Células Cultivadas , Tendinopatía/veterinaria , Tendinopatía/patología
11.
Exp Mol Med ; 56(3): 583-599, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38424192

RESUMEN

Tendinopathy is one of the most common musculoskeletal diseases, and mechanical overload is considered its primary cause. However, the underlying mechanism through which mechanical overload induces tendinopathy has not been determined. In this study, we identified for the first time that tendon cells can release extracellular mitochondria (ExtraMito) particles, a subtype of medium extracellular particles (mEPs), into the environment through a process regulated by mechanical loading. RNA sequencing systematically revealed that oxygen-related reactions, extracellular particles, and inflammation were present in diseased human tendons, suggesting that these factors play a role in the pathogenesis of tendinopathy. We simulated the disease condition by imposing a 9% strain overload on three-dimensional mouse tendon constructs in our cyclic uniaxial stretching bioreactor. The three-dimensional mouse tendon constructs under normal loading with 6% strain exhibited an extended mitochondrial network, as observed through live-cell confocal laser scanning microscopy. In contrast, mechanical overload led to a fragmented mitochondrial network. Our microscopic and immunoblot results demonstrated that mechanical loading induced tendon cells to release ExtraMito particles. Furthermore, we showed that mEPs released from tendon cells overloaded with a 9% strain (mEP9%) induced macrophage chemotaxis and increased the production of proinflammatory cytokines, including IL-6, CXCL1, and IL-18, from macrophages compared to mEP0%, mEP3%, and mEP6%. Partial depletion of the ExtraMito particles from mEP9% by magnetic-activated cell sorting significantly reduced macrophage chemotaxis. N-acetyl-L-cysteine treatment preserved the mitochondrial network in overloaded tendon cells, diminishing overload-induced macrophage chemotaxis toward mEP9%. These findings revealed a novel mechanism of tendinopathy; in an overloaded environment, ExtraMito particles convey mechanical response signals from tendon cells to the immune microenvironment, culminating in tendinopathy.


Asunto(s)
Tendinopatía , Tendones , Ratones , Animales , Humanos , Tendones/patología , Tendinopatía/etiología , Tendinopatía/patología , Inflamación/patología , ARN , Citocinas
12.
J Orthop Surg Res ; 19(1): 130, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38336789

RESUMEN

The diagnosis and management of Achilles tendon ailments continue to be widely discussed by the scientific community. Also, the nomenclature used to describe the tendinopathic lesion in patients changed over the last decades together with the evolution in the knowledge of the physiopathology of Achilles tendinopathy, and unfortunately, through ignorance and possibly laziness, confusion still abounds. To emerge from these foggy paths, some clarifications are still necessary. The present Editorial tries to clarify some of these issues.


Asunto(s)
Tendón Calcáneo , Tendinopatía , Humanos , Tendón Calcáneo/cirugía , Tendón Calcáneo/patología , Tendinopatía/diagnóstico , Tendinopatía/terapia , Tendinopatía/patología , Escocia
13.
Appl Physiol Nutr Metab ; 49(4): 501-513, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38284362

RESUMEN

The aim of this study was to assess the effectiveness of combining sericin with swimming exercise as a treatment for type-I collagenase-induced Achilles tendinopathy (AT) in rats, with a focus on inflammatory cytokines. An experimental AT model was established using type-I collagenase in male Sprague-Dawley rats, categorized into five groups: Group 1 (Control + Saline), Group 2 (AT), Group 3 (AT + exercise), Group 4 (AT + sericin), and Group 5 (AT + sericin + exercise). Intratendinous sericin administration (0.8 g/kg/mL) took place from days 3 to 6, coupled with 30 min daily swimming exercise sessions (5 days/week, 4 weeks). Serum samples were analyzed using ELISA for tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-10 (IL-10), and total antioxidant-oxidant status (TAS-TOS), alongside histopathological and immunohistochemical assessments of Achilles tendon samples. Elevated TNF-α and IL-1ß and decreased IL-10 levels were evident in Group 2; Of these, TNF-α and IL-1ß were effectively reduced and IL-10 increased across all treatment groups, particularly groups 4 and 5. Serum TAS was notably lower in Group 2 and significantly increased in Group 5 compared to Group 2. Histopathologically, Group 2 displayed severe degeneration, irregular fibers, and round cell nuclei, while Group 5 exhibited decreased degeneration and spindle-shaped fibers. The Bonar score increased in Group 2 and decreased in groups 4 and 5. Collagen type-I alpha-1 (Col1A1) expression was notably lower in Group 2 (P = 0.001) and significantly increased in groups 4 and 5 compared to Group 2 (P = 0.011 and 0.028, respectively). This study underscores the potential of sericin and swimming exercises in mitigating inflammation and oxidative stress linked to AT pathogenesis, presenting a promising combined therapeutic strategy.


Asunto(s)
Tendón Calcáneo , Sericinas , Tendinopatía , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Natación , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-10/metabolismo , Sericinas/farmacología , Sericinas/metabolismo , Sericinas/uso terapéutico , Tendón Calcáneo/metabolismo , Tendón Calcáneo/patología , Tendinopatía/tratamiento farmacológico , Tendinopatía/patología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Colagenasas/metabolismo , Colagenasas/uso terapéutico
14.
Am J Phys Med Rehabil ; 103(4): 340-345, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37816189

RESUMEN

OBJECTIVE: This study was conducted to compare the differences in clinical impairments between patients with primary and intrinsic secondary adhesive capsulitis and confirm rotator cuff tendon pathology in intrinsic secondary adhesive capsulitis. DESIGN: This study included 130 patients with unilateral adhesive capsulitis in freezing or frozen stages. Clinical impairment was evaluated using visual analog scale score, shoulder passive range of motion, Cyriax stage, and Constant-Murley score. Plain radiography, ultrasonography, single-contrast arthrography, and intravenous gadolinium-enhanced magnetic resonance imaging were performed in all patients. RESULTS: Among 130 patients, 77 patients were diagnosed as primary adhesive capsulitis and 53 patients as intrinsic secondary adhesive capsulitis. Among intrinsic secondary adhesive capsulitis patients, 44 rotator cuff tendon tears, 6 calcific tendinitis, and 3 rotator cuff tendon tears with calcific tendinitis were observed. No significant intergroup difference was observed in all clinical parameters, including shoulder passive range of motion, visual analog scale, Cyriax stage, and Constant-Murley score. The prevalence of subacromial subdeltoid bursitis was significantly higher in intrinsic secondary adhesive capsulitis compared with primary adhesive capsulitis. CONCLUSIONS: There was no significant difference in all clinical parameters investigated between patients with primary and intrinsic secondary adhesive capsulitis caused by rotator cuff tendon pathology.


Asunto(s)
Bursitis , Lesiones del Manguito de los Rotadores , Articulación del Hombro , Tendinopatía , Humanos , Manguito de los Rotadores/diagnóstico por imagen , Manguito de los Rotadores/patología , Bursitis/diagnóstico por imagen , Bursitis/etiología , Lesiones del Manguito de los Rotadores/diagnóstico por imagen , Lesiones del Manguito de los Rotadores/patología , Tendones , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/patología , Imagen por Resonancia Magnética , Rango del Movimiento Articular , Tendinopatía/diagnóstico por imagen , Tendinopatía/etiología , Tendinopatía/patología
15.
J Orthop Res ; 42(3): 598-606, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37804211

RESUMEN

Tendinopathies account for 30% of 102 million annual musculoskeletal injuries occurring annually in the United States. Current treatments, like dry needling, induce microdamage to promote healing but produce mixed success rates. Previously, we showed focused ultrasound can noninvasively create microdamage while preserving mechanical properties in ex vivo murine tendons. This present study compared growth factor, histological, and mechanical effects after focused ultrasound or dry needling treatments in an in vivo murine tendon injury model. Partial Achilles tenotomy was performed in 26 rats. One-week postsurgery, tendons were treated with focused ultrasound (1.5 MHz, 1-ms pulses at 10 Hz for 106 s, p+ = 49 MPa, p- = 19 MPa) or dry needling (30 G needle, 5 fenestrations over 20 s) and survived for 1 additional week. Blood was collected immediately before and after treatment and before euthanasia; plasma was assayed for growth factors. Treated tendons and contralateral controls were harvested for histology or mechanical testing. No differences were found between treatments in release of insulin growth factor 1 and transforming growth factor beta; vascular endothelial growth factor A concentrations were too low for detection. Histologically, focused ultrasound and dry needling tendons displayed localized fibroblast infiltration without collagen proliferation with no detectable differences between treatments. Mechanically, stiffness and percent relaxation of dry needling tendons were lower than controls (p = 0.0041, p = 0.0441, respectively), whereas stiffness and percent relaxation of focused ultrasound tendons were not different from controls. These results suggest focused ultrasound should be studied further to determine how this modality can be leveraged as a therapy for tendinopathies.


Asunto(s)
Tendón Calcáneo , Tendinopatía , Ratas , Ratones , Animales , Factor A de Crecimiento Endotelial Vascular , Modelos Animales de Enfermedad , Inducción Percutánea del Colágeno , Tendinopatía/terapia , Tendinopatía/patología , Tendón Calcáneo/lesiones
16.
Ann Biomed Eng ; 51(12): 2659-2707, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37899380

RESUMEN

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 ß1, 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.


Asunto(s)
Tendón Calcáneo , Terapia por Luz de Baja Intensidad , Tendinopatía , Humanos , Ratas , Animales , Ratas Wistar , Tendinopatía/patología , Dinoprostona/metabolismo , Factor A de Crecimiento Endotelial Vascular , Colágeno/metabolismo , Tendón Calcáneo/lesiones
17.
J Emerg Med ; 65(4): e307-e309, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37690955

RESUMEN

BACKGROUND: Acute calcific tendinitis (ACT) of the longus colli muscle (LCM) is an inflammatory response due to deposition of calcium hydroxyapatite crystals. It is typically correlated with whiplash and overuse injuries. A common presentation of this inflammatory response is acute but progressive neck pain. It is a rare but important cause of neck pain that should be considered on a differential diagnosis when distinguishing between life-threatening conditions and non-life-threatening causes of neck pain. CASE REPORT: A 51-year-old woman presented to the emergency department (ED) reporting a mild sore throat that progressed to acute neck pain and stiffness. She also reported fatigue, fever, myalgias, and nausea. In the ED, the patient was tachycardic, hypertensive, and mildly febrile with normal oxygen saturation. Examination revealed meningismus and was negative for lymphadenopathy, oropharyngeal findings, and neurologic deficits. Laboratory studies were significant for leukocytosis. Computed tomography (CT) neck was obtained and was notable for calcification of the superior left longus colli muscle with prevertebral and retropharyngeal space edema along the muscle body. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: ACT of the LCM is a benign, self-limited condition that can present with features overlapping emergent causes of acute neck pain. Correct diagnosis relies on characteristic radiographic findings on CT. Fortunately, patients may be discharged home with a short course of anti-inflammatories and corticosteroids with near-complete resolution of symptoms. Emergency physicians, therefore, can rule out life-threatening causes of neck pain, while also making a definitive diagnosis and initiating effective management for this pathology.


Asunto(s)
Dolor Agudo , Tendinopatía , Femenino , Humanos , Persona de Mediana Edad , Dolor de Cuello/etiología , Tendinopatía/complicaciones , Tendinopatía/diagnóstico , Tendinopatía/patología , Tomografía Computarizada por Rayos X , Fiebre/diagnóstico , Diagnóstico Diferencial , Rigidez Muscular , Músculos/patología , Músculos del Cuello/patología
18.
IUBMB Life ; 75(12): 1003-1016, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37503658

RESUMEN

Tendinopathy is a condition characterized by chronic, complex, and multidimensional pathological changes in the tendons. The etiology of tendinopathy is the combination of several factors, and diabetes mellitus (DM) is a risk factor. Increasing evidence has shown that the diabetic microenvironment plays an important role in tendinopathy. However, the mechanism causing tendinopathy in patients with DM remains unclear. Our study found that ferroptosis played an important role in tendinopathy in patients with DM. In vitro, high glucose and high fat treatment was used to simulate the DM microenvironment. Results showed that such a mechanism significantly increased ferroptosis, which was characterized by mass cell death, lipid peroxide accumulation, mitochondrial morphological changes, mitochondrial membrane potential decline, iron overload, and the activation of ferroptosis-related genes, in tendon-derived stem cells cultured in vitro. In the animal studies, db/db mice were used in the DM model, and the db mice had severe tendon injury and high ACSL4 and TfR1 expressions. These phenomena could be alleviated by the ferroptosis inhibitor ferrostatin-1. In conclusion, ferroptosis is associated with tendinopathy in patients with DM, and ferroptosis targeting may be a novel approach for treating diabetic tendinopathy. Our results can provide a new strategy for managing tendinopathy clinically in patients with DM.


Asunto(s)
Diabetes Mellitus , Ferroptosis , Hipercolesterolemia , Tendinopatía , Humanos , Ratones , Animales , Ferroptosis/genética , Tendones/metabolismo , Diabetes Mellitus/patología , Hipercolesterolemia/metabolismo , Tendinopatía/patología , Células Madre/metabolismo
19.
BMC Biol ; 21(1): 132, 2023 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-37280595

RESUMEN

BACKGROUND: Musculoskeletal tissue degeneration impairs the life quality and motor function of many people, especially seniors and athletes. Tendinopathy is one of the most common diseases associated with musculoskeletal tissue degeneration, representing a major global healthcare burden that affects both athletes and the general population, with the clinical presentation of long-term recurring chronic pain and decreased tolerance to activity. The cellular and molecular mechanisms at the basis of the disease process remain elusive. Here, we use a single-cell and spatial RNA sequencing approach to provide a further understanding of cellular heterogeneity and molecular mechanisms underlying tendinopathy progression. RESULTS: To explore the changes in tendon homeostasis during the tendinopathy process, we built a cell atlas of healthy and diseased human tendons using single-cell RNA sequencing of approximately 35,000 cells and explored the variations of cell subtypes' spatial distributions using spatial RNA sequencing. We identified and localized different tenocyte subpopulations in normal and lesioned tendons, found different differentiation trajectories of tendon stem/progenitor cells in normal/diseased tendons, and revealed the spatial location relationship between stromal cells and diseased tenocytes. We deciphered the progression of tendinopathy at a single-cell level, which is characterized by inflammatory infiltration, followed by chondrogenesis and finally endochondral ossification. We found diseased tissue-specific endothelial cell subsets and macrophages as potential therapeutic targets. CONCLUSIONS: This cell atlas provides the molecular foundation for investigating how tendon cell identities, biochemical functions, and interactions contributed to the tendinopathy process. The discoveries revealed the pathogenesis of tendinopathy at single-cell and spatial levels, which is characterized by inflammatory infiltration, followed by chondrogenesis, and finally endochondral ossification. Our results provide new insights into the control of tendinopathy and potential clues to developing novel diagnostic and therapeutic strategies.


Asunto(s)
Tendinopatía , Transcriptoma , Humanos , Tendones/patología , Tendinopatía/genética , Tendinopatía/patología , Células Madre , Diferenciación Celular
20.
J Proteome Res ; 22(6): 1712-1722, 2023 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-37159428

RESUMEN

Tendinopathy is a disease with surging prevalence. Lacking understanding of molecular mechanisms impedes the development of therapeutic approaches and agents. Lysine lactylation (Kla) is a newly discovered post-translational modification related to glycolysis. It has long been noted that manipulation of glycolysis metabolism could affect tendon cell function, tendon homeostasis, and healing process of tendon. However, protein lactylation sites in tendinopathy remain unexplored. Here, we conducted the first proteome-wide Kla analysis in tendon samples harvested from patients with rotator cuff tendinopathy (RCT), which identified 872 Kla sites across 284 proteins. Compared with normal counterparts, 136 Kla sites on 77 proteins were identified as upregulated in the pathological tendon, while 56 sites on 32 proteins were downregulated. Function enrichment analysis demonstrated that the majority of proteins with upregulated Kla levels functioned in organization of the tendon matrix and cholesterol metabolism, accompanied by lower expression levels which meant impaired cholesterol metabolism and degeneration of the tendon matrix, indicating potential cross-talk between protein lactylation and expression levels. At last, by western blotting and immunofluorescence, we verified the correlation between high lactylation and the downregulation of matrix and cholesterol-related proteins including BGN, MYL3, TPM3, and APOC3. ProteomeXchange: PXD033146.


Asunto(s)
Manguito de los Rotadores , Tendinopatía , Humanos , Manguito de los Rotadores/metabolismo , Manguito de los Rotadores/patología , Proteínas/metabolismo , Tendones/metabolismo , Tendones/patología , Lisina/metabolismo , Tendinopatía/genética , Tendinopatía/metabolismo , Tendinopatía/patología
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