RESUMO
When compared to placebo, acetaminophen (APAP) reduces tendon stiffness and collagen cross-linking. APAP also enhances the exercise-induced increase in peritendinous levels of IL-6. Elevated levels of IL-6 are associated with tendinopathy, thus we hypothesized that chronic, elevated peritendinous IL-6 would alter tendon extracellular matrix (ECM). IL-6 (â¼3000pgml-1) was injected (3dwk-1 for 8-wks) into the Achilles peritendinous region of male Wistar rats (n=16) with the opposite leg serving as a sham. Fractional synthesis rates (FSR) were determined using deuterium oxide. Collagen (hydroxyproline) and hydroxylysl pyridinoline (HP) cross-linking were analyzed by HPLC. ECM and IL-6 related genes were evaluated using qRT-PCR. Relative to sham, collagen (Col) 1a1 but not Col3a1 expression was suppressed (47%) in tendons exposed to IL-6 (p<0.05). Lysyl oxidase (LOX) and MMP-1 expression were also reduced (37%) in IL-6 treated tendons (p<0.05). Relative to sham the expression of MMP-2, -3, -9, and TIMP-1 were not altered by IL-6 treatment (p>0.05). Interleukin-6 receptor subunit beta precursor (IL6st) was lower (16%) in IL-6 treated tendons when compared to sham (p<0.05). Suppressor of cytokine signaling 3 (Socs3), signal transducer and activator of transcription 3 (STAT3), and protein inhibitor of activated STAT 1 (Pias1) were not altered by IL-6 exposure (p>0.05). Neither collagen nor cross-linking content were altered by IL-6 (p>0.05). Additionally, IL-6 treatment did not alter tendon FSR. Chronic treatment with physiologically relevant levels of IL-6 suppresses expression of Col1a1 and LOX while also altering expression of select MMPs but does not alter Achilles tendon collagen synthesis.
Assuntos
Tendão do Calcâneo/metabolismo , Matriz Extracelular/metabolismo , Interleucina-6/farmacologia , Tendão do Calcâneo/patologia , Animais , Colágeno Tipo I/biossíntese , Cadeia alfa 1 do Colágeno Tipo I , Colágeno Tipo III/biossíntese , Receptor gp130 de Citocina/biossíntese , Matriz Extracelular/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Proteínas Inibidoras de STAT Ativados/biossíntese , Proteína-Lisina 6-Oxidase/metabolismo , Ratos , Ratos Wistar , Fator de Transcrição STAT3/biossíntese , Proteína 3 Supressora da Sinalização de Citocinas/biossíntese , Inibidor Tecidual de Metaloproteinase-1/biossínteseRESUMO
Purpose: To determine the rate of and risk factors for clinical failure and return to military duty following primary patellar tendon repair with either transosseous trunnel repair or suture anchor repair. Methods: The Military Health System Data Repository (MDR) was queried to identify all adult patients undergoing surgical treatment of a patellar tendon rupture in the Military Health System from 2014 to 2018. Patients who underwent either transosseous tunnel repair or suture anchor repair were included. Health records were examined to collect additional data. Univariate analysis and multivariate logistic regression models were used to determine independent risk factors for rerupture. Results: A total of 450 knees in 437 patients were included. Transosseous tunnel repair was the most frequently used technique (314/450, 77%), followed by suture anchor repair (113/450, 25%). Rerupture occurred in 33 knees (7%). There was no difference in rerupture rate between transosseous tunnel repair and suture anchor repair (P = .15), and this result persisted within the multivariate logistic regression model. Among transosseous tunnel repairs, use of low tensile strength suture was an independent risk factor for repair failure (odds ratio [OR], 3.4; P = .016). Among suture anchor repairs, use of anchors 5.0 mm in diameter or greater (OR, 12.0; P = .027) was an independent risk factor for repair failure. Conclusions: There is no statistically significant difference in failure rate between transosseous tunnel repair and suture anchor repair in primary patellar tendon ruptures. However, the use of low tensile strength suture with transosseous tunnels and the use of suture anchors 5.0 mm in diameter or greater resulted in significantly higher failure rates. These data suggest that use of high tensile strength suture in transosseous tunnel repair and use of suture anchors less than 5.0 mm in diameter in suture anchor repair result in lower failure rate in primary patellar tendon repair. Level of Evidence: Level III, retrospective cohort study.
RESUMO
Several recent investigations have demonstrated that the ability of various tendons to alter structural and functional properties in response to exercise are muted in women compared with men. We hypothesize that this disparity between men and women may be due to a reduced tendon production of key mediators of tendon extracellular matrix (ECM) remodeling in response to mechanical loading, e.g., exercise. Using microdialysis before and after an acute bout of resistance exercise, we evaluated Achilles peritendinous levels of insulin-like growth factor-1 (IGF-1) and interleukin-6 (IL-6), which have both been shown to increase tendon collagen synthesis. Additionally, the matrix remodeling enzymes matrix metalloproteinase-2 (MMP-2), MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) were also evaluated. IGF-1 levels were elevated (P < 0.05) to a similar extent in men and women after 3 h of exercise but remained elevated at 4 h in only women. IL-6 levels were ~4-fold greater after exercise in both men and women (P < 0.05). MMP-2 levels increased to a similar extent (~2-3-fold) in men and women (P < 0.05). In contrast, MMP-9 increased with exercise but only in men (P < 0.05). Last, TIMP-1 levels also increased (P < 0.05) with exercise in men and women but the increase was more prolonged in women. In conclusion, we observed modest sex differences in tendon release of MMP-9, TIMP-1, and IGF-1 after acute resistance exercise. If such differences persist throughout a chronic exercise training, they may contribute to the reduced ability of women to adapt to exercise compared with men.NEW & NOTEWORTHY In this investigation we utilized microdialysis of the peritendinous Achilles to evaluate potential differences between men and women in tendon production of key regulators of extracellular matrix remodeling. We demonstrate that a modest sex-specific difference exists in peritendinous levels of several key extracellular matrix modulators after an acute bout of resistance exercise.
Assuntos
Tendão do Calcâneo/metabolismo , Exercício Físico/fisiologia , Fator de Crescimento Insulin-Like I/metabolismo , Metaloproteinases da Matriz/metabolismo , Adulto , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Feminino , Humanos , Interleucina-6/metabolismo , Masculino , Treinamento Resistido/métodos , Caracteres Sexuais , Inibidor Tecidual de Metaloproteinase-1/metabolismoRESUMO
PURPOSE: This study aimed to assess the ability for exercise training performed before and during biweekly doxorubicin (DOX) administration to attenuate adverse effects of DOX on skeletal muscle. We hypothesized that DOX treatment would increase REDD1, impair mammalian target of rapamycin (mTOR) signaling, and reduce muscle fiber size, and that exercise training would attenuate these responses. METHODS: Eight-week-old ovariectomized female Sprague-Dawley rats were randomized to one of four treatments: exercise + DOX (Ex-Dox), Ex + vehicle (Ex-Veh), sedentary + DOX (Sed-Dox), and Sed + Veh (Sed-Veh). DOX (4 mg·kg) or vehicle (saline) intraperitoneal injections were performed biweekly for a total of three injections (cumulative dose, 12 mg·kg). Ex animals performed interval exercise (4 × 4 min, 85%-90% VËO2peak) 5 d·wk starting 1 wk before the first injection and continued throughout study duration. Animals were euthanized ~5 d after the last injection, during which the soleus muscle was dissected and prepared for immunoblot and immunohistochemical analyses. RESULTS: REDD1 mRNA and protein were increased only in Sed-Dox (P < 0.05). The phosphorylation of mTOR and 4E-BP1 and MHC I and MHC IIa fiber size were lower in Sed-Dox versus Sed-Veh (P < 0.05). By contrast, REDD1 mRNA and protein, mTOR, 4E-BP1, and MHC I fiber size were not different between Ex-Dox and Ex-Veh (P > 0.05). LC3BI was higher, and the LC3BII/I ratio was lower in Sed-Dox versus Sed-Veh (P < 0.05) but not between Ex-Dox and Ex-Veh (P > 0.05). CONCLUSION: These data suggest that DOX may inhibit mTORC1 activity and reduce MHCI and MHCIIa fiber size, potentially through elevated REDD1, and that exercise may provide a therapeutic strategy to preserve skeletal muscle size during chronic DOX treatment.