Effect of methylprednisolone use on the rotator cuff in rats: biomechanical and histological study

Ghellioni, Gustavo Vinícius; Silva, Lucas Souto da; Piovezan, Anna Paula; Martins, Rafael Olívio

doi:10.1016/j.rboe.2015.05.002

Cited by 3 publications

(6 citation statements)

References 13 publications

(15 reference statements)

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“…These changes included loss of cellular orientation, increased polygonal and flattened appearance of cells, and decreased vascular proliferation. These changes were observed at IMPACT OF CSI ON ROTATOR CUFF TENDONS e165 7 days 33 but not 21 days after low dose corticosteroid exposure. 18,22 However, the histologic appearance did not return to normal at 21 days after high-dose corticosteroid exposure.…”

Section: Histologicmentioning

confidence: 87%

“…Nuelle et al 32 Y Peritendinous injection of lidocaine, betamethasone, and methylprednisolone results in significant supraspinatus tenotoxicity in vitro. Ghellioni et al 33 Y Y There is a dose-dependent reduction of mechanical resistance and histological modifications of rotator cuff tendon exposed to corticosteroids.…”

Section: Systematic Review and Study Inclusionmentioning

confidence: 97%

“…All 5 biomechanical studies were performed on a rat model. Four of these reported a significant decrease in load to failure and stiffness in healthy and injured tendons treated with CSIs compared with a control 12,30,31,33 or with hyaluronic acid. 23 In addition to showing altered RCT biomechanics, the study by Maman et al 31 also demonstrated significantly decreased greater tuberosity bone volume density on micro-computed tomography 1 week after 3 consecutive methylprednisolone acetate injections.…”

Section: Biomechanicalmentioning

confidence: 99%

“…Several studies showed molecular effects of decreased cellular proliferation/senescence and decreased capacity for tendon repair and cellular migration, and thus healing 23,24,27 (Table 2). 18e28, 32,33 These effects on cellular proliferation were visualized directly at 48 and 96 hours after treatment and demonstrated indirectly by decreased proliferating cell nuclear antigen (a protein essential for DNA replication and repair) expression 2 weeks after corticosteroid exposure. 23,27 Decreased capacity for physiologic tendon repair and cellular migration was demonstrated by decreased levels of matrix metalloproteinase (MMP) and increased levels of tissue inhibitors of metalloproteinases after exposure to corticosteroids.…”

Section: Molecularmentioning

confidence: 99%

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Adverse Impact of Corticosteroids on Rotator Cuff Tendon Health and Repair: A Systematic Review of Basic Science Studies

Puzzitiello

Patel

Forlenza

et al. 2020

Arthroscopy, Sports Medicine, and Rehabilitation

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Purpose: To evaluate the in vitro effects of corticosteroid injections (CSIs) on rotator cuff tendon (RCT). Methods: A systematic review of the MEDLINE database was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for all studies reporting on adverse biochemical and biomechanical effects of CSIs on RCT. Results: Sixteen studies were identified that had been published in the last 15 years on the effects of corticosteroids on RCTs. Eight of these studies were on human RCTs, 6 were on rat tendons, 1 considered both human and rat tendons, and 1 was on dog tendon. Five studies analyzed the effects of corticosteroids on the biomechanical properties of RCT or rotator cuff repair, whereas the remaining observed the cellular and molecular effects of CSIs on RCT. Corticosteroids suppress an inflammatory response, induce apoptosis, and have negative effects on collagen and tendon cell viability in RCTs. The mechanical properties, including load to failure of RCTs and rotator cuff repair anchor pull-out strength, also are decreased by CSIs. These in vitro effects appear to be transient as well as frequency and dose dependent. Conclusions: On a molecular level, CSIs decrease cellular proliferation, alter collagen and extracellular matrix composition, impede inflammatory pathways, decrease cellular viability, increase adipocyte differentiation, and increase apoptosis. These changes can be seen as early as 24 hours after corticosteroid exposure, last as long as 2 to 3 weeks, and are exacerbated by increased doses and decreased latency between doses. Biomechanical studies demonstrate that these changes result in decreased maximal load to failure, tendon stiffness, and suture anchor pull-out strength in rat shoulders up to 2 weeks but not at 3 and 4 weeks, post-CSI. Clinical Relevance: Shoulder subacromial steroid injection is common, and practitioners should be aware of results both positive and deleterious.R otator cuff tendon (RCT) pathology is the most common cause of shoulder pain. 1 Rotator cuff tendinosis, which refers to processes such as impingement, rotator cuff fraying, partial-thickness tears, and tendinitis, is a normal element of human aging. 1,2 While often asymptomatic, RCT pathology can be a source of pain and significantly impact patients' quality of life. 3 Corticosteroid injections (CSIs) into the subacromial space have served as a valuable treatment modality to the physician treating patients with RCT pathology refractory to conservative management, as they have demonstrated to improve symptoms in the short term. 3e6 However, CSIs have failed to consistently provide long-term pain relief, and recent studies suggest that CSIs may even predispose to worse longterm outcomes, such as pathologic progression or surgical failure. 4,5,7e9

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Section: Histologicmentioning

confidence: 87%

Section: Systematic Review and Study Inclusionmentioning

confidence: 97%

Section: Biomechanicalmentioning

confidence: 99%

Section: Molecularmentioning

confidence: 99%

See 2 more Smart Citations

Adverse Impact of Corticosteroids on Rotator Cuff Tendon Health and Repair: A Systematic Review of Basic Science Studies

Puzzitiello

Patel

Forlenza

et al. 2020

Arthroscopy, Sports Medicine, and Rehabilitation

View full text Add to dashboard Cite

show abstract

“…For MP therapy, the range of the applied dosage in rodent is from 1 mg kg −1 to 40 mg kg −1 (Ghellioni et al, 2015 ; Ren et al, 2015 ). In 2010, Guess et al have suggested that short-term, high-dose glucocorticoid treatment resulted in similar changes in gene expression and glucocorticoid receptor phosphorylation to that of long-term, low-dose glucocorticoid treatment (Guess et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Methylprednisolone Protects Cardiac Pumping Mechanics from Deteriorating in Lipopolysaccharide-Treated Rats

Tsai

Chang

et al. 2015

Front. Physiol.

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It has been shown that a prolonged low-dose corticosteroid treatment attenuates the severity of inflammation and the intensity and duration of organ system failure. In the present study, we determined whether low-dose methylprednisolone (a synthetic glucocorticoid) can protect male Wistar rats against cardiac pumping defects caused by lipopolysaccharide-induced chronic inflammation. For the induction of chronic inflammation, a slow-release ALZET osmotic pump was subcutaneously implanted to infuse lipopolysaccharide (1 mg kg−1 d−1) for 2 weeks. The lipopolysaccharide-challenged rats were treated on a daily basis with intraperitoneal injection of methylprednisolone (5 mg kg−1 d−1) for 2 weeks. Under conditions of anesthesia and open chest, we recorded left ventricular (LV) pressure and ascending aortic flow signals to calculate the maximal systolic elastance (Emax) and the theoretical maximum flow (Qmax), using the elastance-resistance model. Physically, Emax reflects the contractility of the myocardium as an intact heart, whereas Qmax has an inverse relationship with the LV internal resistance. Compared with the sham rats, the cardiodynamic condition was characterized by a decline in Emax associated with the increased Qmax in the lipopolysaccharide-treated rats. Methylprednisolone therapy increased Emax, which suggests that the drug may have protected the contractile status from deteriorating in the inflamed heart. By contrast, methylprednisolone therapy considerably reduced Qmax, indicating that the drug may have normalized the LV internal resistance. In parallel, the benefits of methylprednisolone on the LV systolic pumping mechanics were associated with the reduced cardiac levels of negative inotropic molecules such as peroxynitrite, malondialdehyde, and high-mobility group box 1 protein. Based on these data, we suggested that low-dose methylprednisolone might prevent lipopolysaccharide-induced decline in cardiac intrinsic contractility and LV internal resistance, possibly through its ability to reduce the aforementioned myocardial depressant substances. However, since our results were obtained in anesthetized open-chest rats, extrapolation to what may occur in conscious intact animals should be done with caution.

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Expression of Collagen (Types I, III, and V), HSP47, MMP-2, and TIMP-1 in Retrobulbar Adipose Tissue of Patients with Thyroid-Associated Orbitopathy

Luo

Liu

Yang

et al. 2020

Journal of Ophthalmology

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Objective. This study aimed to investigate the expression of collagen (types I, III, and V), heat shock protein 47 (HSP47), matrix metalloproteinase-2 (MMP-2), and tissue inhibitors of metalloproteinase-1 (TIMP-1) in the retrobulbar adipose tissues of patients with thyroid-associated orbitopathy (TAO). Materials and Methods. The retrobulbar adipose tissues were collected from 4 TAO patients undergoing orbital decompression and 4 ocular enucleation patients with atrophic eyeball caused by ocular trauma between May 2019 and September 2019. Masson staining was performed to analyze the differences in collagen expression and degree of histologic fibrosis in each sample. The protein expressions of collagen (types I, III, and V), HSP47, MMP-2, and TIMP-1 were determined by western blotting. The data of western blotting were analyzed using SPSS version 17.0, with independent t-tests. Results. The results of Masson staining showed that the expression of collagen fibers in the TAO group was significantly higher than that in the control group, and the fibers were diffuse and irregular in distribution. The expression level of collagen (types I, III, and V), HSP47, MMP-2, and TIMP-1 in the TAO group were significantly higher than that in the control group (P<0.05). Conclusion. The proliferation and fibrosis of retrobulbar adipose tissue in TAO patients might be related to the increased expression of collagen (types I, III, and V) and HSP47 and decreased degradation of extracellular matrix.

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Effect of methylprednisolone use on the rotator cuff in rats: biomechanical and histological study

Cited by 3 publications

References 13 publications

Adverse Impact of Corticosteroids on Rotator Cuff Tendon Health and Repair: A Systematic Review of Basic Science Studies

Adverse Impact of Corticosteroids on Rotator Cuff Tendon Health and Repair: A Systematic Review of Basic Science Studies

Methylprednisolone Protects Cardiac Pumping Mechanics from Deteriorating in Lipopolysaccharide-Treated Rats

Expression of Collagen (Types I, III, and V), HSP47, MMP-2, and TIMP-1 in Retrobulbar Adipose Tissue of Patients with Thyroid-Associated Orbitopathy

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