Knockdown of S100A11 Inhibits H<sub>2</sub>O<sub>2</sub>-Induced Oxidative Stress and Cellular Damage in Human Tenocytes
Rotator cuff tears (RCTs) are a leading cause of shoulder pain and dysfunction, often linked to oxidative stress and chronic inflammation. However, the molecular mechanisms underlying these pathological processes are not yet fully understood. S100A11, a calcium-binding protein of the S100 family, has been implicated in various inflammatory and degenerative diseases, but its role in RCTs is still unclear. In this study, we investigated the function of S100A11 in hydrogen peroxide H2O2-induced oxidative and inflammatory injury in human tenocytes. Our results demonstrated that S100A11 expression was significantly upregulated in tendon tissues from RCT patients. Knockdown of S100A11 markedly inhibited H2O2-induced inflammatory responses by reducing iNOS and PGE2 levels and improved tenocyte viability. Furthermore, silencing S100A11 alleviated oxidative stress. Mechanistically, S100A11 knockdown activated the PI3K/Akt signaling pathway, suggesting a protective regulatory role. These findings highlight S100A11 as a potential therapeutic target for mitigating oxidative damage and promoting tendon repair in rotator cuff injuries.
- Research Article
99
- 10.1016/j.jse.2015.05.031
- Jul 22, 2015
- Journal of shoulder and elbow surgery
Rotator cuff tears in young patients: a different disease than rotator cuff tears in elderly patients
- Preprint Article
- 10.20944/preprints202507.0915.v1
- Jul 10, 2025
- Preprints.org
Research has highlighted the importance of assessing movement-evoked pain (MEP) to elucidate the underlying mechanisms and refine treatments in musculoskeletal pain. Rotator cuff (RC) tears are a common cause of shoulder pain, and these patients often experience pain at rest, which worsens during arm movements. Temporal summation (TS) examines the neuronal mechanisms underlying ascending pain facilitation, which may be related to MEP in individuals with RC tears. Our objective was to explore the relationships among TS, pain at rest, and MEP in individuals with symptomatic RC tears. This study involved eighty-five participants diagnosed with symptomatic RC tears. Spearman’s rank correlation coefficient was used to assess the relationships among TS, pain at rest, and movement-evoked pain. Logistic regression was performed to determine the associations within the subgroups of individuals with acute and chronic pain. A weak correlation between the TS and MEP (r = 0.23) was observed. There was also a weak, statistically significant correlation between pain at rest and MEP (r = 0.30). However, there was no correlation between TS and pain at rest (r=0.04). These findings suggest that MEP and TS represent partially independent pain mechanisms in RC tear patients and should be assessed separately in clinical practice.
- Research Article
5
- 10.11005/jbm.2017.24.4.235
- Nov 1, 2017
- Journal of Bone Metabolism
BackgroundAuthors assessed lean body mass (fat free tissue), upper and lower, and bone mineral density (BMD) in patients of osteoporotic bone distal radius fracture (DRF) and degenerative rotator cuff tear (RCT) patients of shoulder. We predict inferior muscle mass and osteoporosis are more frequent in DRF group than RCT group.MethodsBetween January 2016 and June 2017, overall 38 of DRF and 30 of RCT were eligible for this retrospective comparison study after excluding of patients with compounding factors. BMD and other body composition, fat and lean body mass, were assessed with a single dual energy X-ray absorptiometry in one hospital.ResultsT-score of spine were −2.2 and −1.6 in DRF and RCT patients with significant difference (P=0.040). Final BMD score, lower score of patient between spine and femoral score, of both group also presented difference with significance, −2.4 of DRF and −1.9 of RCT patients (P=0.047). Diagnosis of osteoporosis was confirmed in 19 patients (50%) from DRF compared with 9 patients (30%) from RCT. The mean lean soft tissue mass of the arm was 3.7 kg and 3.8 kg in the DRF and RCT, respectively, without significant difference (P=0.882). The mean lean body mass of the leg was 11.0 kg and 10.5 kg in the DRF and RCT, respectively, without significant difference (P=0.189). The relative overall appendicular lean mass was not significantly different between groups.ConclusionsEven though BMD difference, we did not find muscle mass difference between DRF and RCT patients.
- Abstract
- 10.1016/j.jval.2020.04.726
- May 1, 2020
- Value in Health
PMS40 REAL-WORLD TREATMENT PATTERNS AND ECONOMIC BURDEN OF ROTATOR CUFF TEAR PATIENTS IN THE US
- Research Article
12
- 10.1016/j.jos.2019.02.016
- Apr 1, 2019
- Journal of Orthopaedic Science
Arthroscopic repair of large to massive rotator cuff tears in patients younger than 60 years
- Research Article
28
- 10.1016/j.jse.2018.05.042
- Aug 13, 2018
- Journal of Shoulder and Elbow Surgery
Blood flow evaluation by dynamic magnetic resonance imaging of symptomatic rotator cuff tears and frozen shoulders
- Research Article
12
- 10.3928/01477447-20121217-17
- Jan 1, 2013
- Orthopedics
Subscapularis tendon tears are a well-established cause of shoulder pain. The objective of the current study was to evaluate the associated shoulder pathology in patients with full-thickness subscapularis tendon tears using magnetic resonance imaging. Forty-seven magnetic resonance imaging studies taken between 2008 and 2009 with a diagnosis of full-thickness subscapularis tendon tears were reviewed. The size of the subscapularis tendon tear, amount of muscle volume loss, Goutallier grade, biceps tendon pathology, coracohumeral distance, and associated rotator cuff tears were recorded. Statistical analysis was performed. Patients 55 years and older vs those 54 years and younger had an average subscapularis tear size of 35 vs 19 mm, an average Goutallier grade of 2.7 vs 0.8, and a total muscle volume loss of 25% vs 5%, respectively. Patients with a dislocated vs normal biceps tendons had an average subscapularis tear size of 37 vs 23 mm, an average Goutallier grade of 3 vs 0.9, and a total muscle volume loss of 28% vs 7%, respectively. Patients with vs without concomitant rotator cuff tears had an average subscapularis tear size of 32 vs 17 mm, an average Goutallier grade of 2.3 vs 0.6, and a total muscle volume loss of 21% vs 3%, respectively. Overall average coracohumeral distance measured in the axial plane was 10.8±4.6 mm. Average coracaohumeral distance was 14.8 vs 8.1 mm in patients with a Goutallier grade of 0 vs 3 or 4, resepectively, and 13.6 vs 8.5 mm in patients with no rotator cuff tear vs those with a supra- and infraspinatus tear, respectively. Increased age, dislocated biceps tendons, and concomitant rotator cuff tears in patients with full-thickness subscapularis tendon tears are associated with larger subscapularis tendon tear size, higher Goutallier grades, and increased subscapularis muscle volume loss. Decreased coracohumeral distance is associated with a higher Goutallier grade and rotator cuff tears.
- Research Article
4
- 10.1186/s12920-022-01292-y
- Jun 20, 2022
- BMC Medical Genomics
BackgroundThis study aimed to identify the differentially expressed mRNAs and lncRNAs in inflammatory long head of biceps tendon (LHBT) of rotator cuff tear (RCT) patients and further explore the function and potential targets of differentially expressed lncRNAs in biceps tendon pathology.MethodsHuman gene expression microarray was made between 3 inflammatory LHBT samples and 3 normal LHBT samples from RCT patients. GO analysis and KEGG pathway analysis were performed to annotate the function of differentially expressed mRNAs. The real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was admitted to verify their expression. LncRNA-mRNA co-expression network, cis-acting element, trans-acting element and transcription factor (TF) regulation analysis were constructed to predict the potential molecular regulatory mechanisms and targets for LHB tendinitis.Results103 differentially expressed lncRNAs and mRNAs, of which 75 were up-regulated and 28 were down-regulated, were detected to be differentially expressed in LHBT. The expressions of 4 most differentially expressed lncRNAs (A2MP1, LOC100996671, COL6A4P, lnc-LRCH1-5) were confirmed by qRT-PCR. GO functional analysis indicated that related lncRNAs and mRNAs were involved in the biological processes of regulation of innate immune response, neutrophil chemotaxis, interleukin-1 cell response and others. KEGG pathway analysis indicated that related lncRNAs and mRNAs were involved in MAPK signaling pathway, NF-kappa B signaling pathway, cAMP signaling pathway and others. TF regulation analysis revealed that COL6A4P2, A2MP1 and LOC100996671 target NFKB2.ConclusionsLlncRNA-COL6A4P2, A2MP1 and LOC100996671 may regulate the inflammation of LHBT in RCT patients through NFKB2/NF-kappa B signaling pathway, and preliminarily revealed the pathological molecular mechanism of tendinitis of LHBT.
- Research Article
1
- 10.7860/jcdr/2021/48773.14845
- Jan 1, 2021
- JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH
Introduction: Shoulder joint is a highly mobile joint but is prone for rotator cuff injuries and dislocations. It is necessary to accurately diagnose rotator cuff and labral injuries so that appropriate plan of action for treatment can be taken. Magnetic Resonance Imaging (MRI) can be used to diagnose and describe the extent of rotator cuff tendon and labral injuries and any secondary rotator cuff muscle abnormalities. Aim: To study the demographic profile of patients presenting with shoulder pain and instability, identify the various rotator cuff injuries causing shoulder pain, identify the rotator cuff interval lesions causing microinstability, identify the various labral and bony pathologies in instability, describe the MRI features of the rotator cuff, rotator cuff interval, labral and bony injuries. Materials and Methods: This study was a cross-sectional study of patients with symptoms of either shoulder pain or instability who underwent MRI evaluation of the shoulder in the Department of Radiodiagnosis, Rajarajeswari Medical College and Hospital, Bengaluru, Karnataka, India, from July 2018 to December 2020. The study population consisted of 54 patients with either shoulder pain or instability who underwent MRI of shoulder. All the MRI scans of the shoulder in this study were performed using 1.5 Tesla Siemens Magnetom Avanto (Tim 76x18) MR machine using a flex coil. Results: The study population consisted of 54 patients comprising of 38 males and 16 females. The age of the patients ranged from 20-77 years. Majority of the patients were older than 50 years constituting about 33.33% of the total study population. Rotator cuff injury was the commonest cause of pain. Tendinosis was the commonest type of rotator cuff injury followed by partial-thickness and full-thickness tendon tears. The commonest grade of tendinosis was mild or grade 1. Supraspinatus tendon was the most commonly affected tendon followed by subscapularis and infraspinatus tendons. Teres minor tendon was normal in all the cases. Anterior instability was the commonest type of instability with equal prevalence of soft tissue Bankart, bony Bankart and Perthes lesions. Biceps pulley lesions resulted in long head of biceps tendon instability, microinstability and internal impingement. Conclusion: Rotator cuff injuries are the commonest cause of shoulder pain and are seen more frequently after the fifth decade. Shoulder instability is most commonly seen in young male adults. Tendinosis is the commonest type of rotator cuff injury. Supraspinatus tendon is the most commonly injured tendon. Anterior instability is the commonest type of shoulder instability. Biceps pulley lesions result in long head of biceps tendon instability, microinstability and internal impingement. MRI can diagnose interstitial or intrasubstance tendon tears which are not visualised on arthroscopy. MRI description of tendon and labral tears, tendon retraction and muscle atrophy can guide the orthopaedician during arthroscopy and in treatmentplanning.
- Research Article
22
- 10.1016/j.arthro.2014.05.011
- Jul 23, 2014
- Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association
Repair of Full-Thickness Rotator Cuff Tears in Patients Aged Younger Than 55 Years
- Research Article
8
- 10.1080/00325481.2023.2241343
- Jul 29, 2023
- Postgraduate Medicine
Introduction A significant number of rotator cuff tear (RCT) patients developed chronic shoulder pain that did not correspond to physiological changes. Central sensitization syndrome (CSS) is a neurophysiological adaptation process that can result in hypersensitivity to peripheral stimuli. Although there is evidence of an association between CSS and musculoskeletal problems, no studies have focused on the association between CSS and RCT. The primary purpose of this study was to examine the prevalence of CSS in patients with RCT. The secondary purpose was to document the associated conditions and comorbidity that were associated with the CSS. Methods This was a cross-sectional study of patients with RCT who completed the Central Sensitization Inventory (CSI). Patients with score of ≥ 40/100 were considered positive for CSS. Demographic and clinical data and CSI results were collected to analyze the prevalence and associated factors of CSS in RCT patients. Results A total of 404 RCT patients were included, and the CSS prevalence was 39.4%. Compared to the non-CSS group, the CSS group had an odds ratio of 4.13 (95% CI, 2.70–6.32; p<0.001) for ages 51–60, 3.07 (95% CI, 2.00–4.69; p<0.001) for symptoms lasting more than 6 months, 6.08 (95% CI, 3.90–9.47; p<0.001) for nonphysical laborers, 3.69 (95%CI, 2.42–5.61; p<0.001) for long head of biceps (LHB) abnormality, 2.93 (95% CI, 1.93–4.45; p<0.001) for concurrent shoulder stiffness, 4.82 (95% CI, 2.55–9.10; p<0.001) for anxiety or panic episodes, and 2.11 (95% CI, 1.12, 4.00; p<0.001) for depression. Conclusions The prevalence of CSS in patients with RCT was relatively high at 39.4%. The CSS was associated with higher age, female gender, and clinical findings of symptoms lasting over six months, nonphysical laborers, abnormal LHB, concurrent shoulder stiffness, anxiety, and depression.
- Research Article
1
- 10.1016/j.jbiomech.2024.112055
- Mar 1, 2024
- Journal of Biomechanics
Glenohumeral biomechanics after rotator cuff (RC) tears have not been fully elucidated. This study aimed to investigate the muscle compensatory mechanism in weight-bearing shoulders with RC tears and asses the induced pathomechanics (i.e., glenohumeral translation, joint instability, center of force (CoF), joint reaction force).An experimental, glenohumeral simulator with muscle-mimicking cable system was used to simulate 30° scaption motion. Eight fresh-frozen shoulders were prepared and mounted in the simulator. Specimen-specific scapular anthropometry was used to test six RC tear types, with intact RC serving as the control, and three weight-bearing loads, with the non-weight-bearing condition serving as the control. Glenohumeral translation was calculated using instantaneous helical axis. CoF, muscle forces, and joint reaction forces were measured using force sensors integrated into the simulator. Linear mixed effects models (RC tear type and weight-bearing) with random effects (specimen and sex) were used to assess differences in glenohumeral biomechanics.RC tears did not change the glenohumeral translation (p > 0.05) but shifted the CoF superiorly (p ≤ 0.005). Glenohumeral translation and joint reaction forces increased with increasing weight bearing (p < 0.001). RC and deltoid muscle forces increased with the presence of RC tears (p ≤ 0.046) and increased weight bearing (p ≤ 0.042).The synergistic muscles compensated for the torn RC tendons, and the glenohumeral translation remained comparable to that for the intact RC tendons. However, in RC tears, the more superior CoF was close to where glenoid erosion occurs in RC tear patients with secondary osteoarthritis. These findings underscore the importance of early detection and precise management of RC tears.
- Research Article
50
- 10.1080/03007995.2021.1918074
- May 14, 2021
- Current Medical Research and Opinion
Objective This retrospective study examined treatment characteristics and the economic burden associated with rotator cuff tears (RCT) and rotator cuff repairs (RCR). Additionally, this study aimed to explore the economic implications associated with delayed surgical intervention. Methods Adult RCT patients meeting eligibility criteria were identified from 1/1/2013–6/30/2017 using the IBM Watson Health MarketScan Commercial database. Patients with incident RCR within 12 months post-index and 12 months continuous enrollment after the RCR date were also analyzed. Early surgery was defined as RCR within 6 months and 1 month from the partial-thickness tear and full-thickness tear diagnoses, respectively. Patient characteristics, all-cause direct costs (plan paid and patient out-of-pocket), RCT-related costs, pre-surgical costs, post-surgical costs, and healthcare resource utilization were reported by RCT type. Attributable indirect costs, absenteeism and short-term disability (STD), were also estimated. Results 102,488 RCT patients were identified (partial-thickness tears: 46,856 [45.7%]; full-thickness tears: 55,632 [54.3%]). Fifty per cent RCT patients underwent RCR within 12-months of diagnosis. Full-thickness RCT patients had an average total baseline (one year pre-diagnosis) and post-index costs of $17,096 and $32,110, respectively. Similarly, partial thickness patients had baseline costs of $16,385 and post-index costs of $27,017. Mean all-cause annual post-surgery costs were $34,086 for patients with partial-thickness tears and $34,249 for patients with full-thickness tears, of which 40% and 38% of costs were RCT-related, respectively. Productivity losses due to absenteeism and STD in the 12-month post-surgery period averaged $5843 and $4493, respectively, for partial-thickness tear patients and $5770 and $4382, respectively, for full-thickness tear patients. Average additional spending per delayed surgical patient between diagnosis and surgery was $8524 and $3213 (both p <0.001) for partial- and full-thickness tear patients, respectively. Conclusions This exploratory analysis indicates considerable RCT and RCR economic burden to the healthcare system. High healthcare utilization and costs highlight the importance of efficiently managing patients with RCT diagnosis. Data also suggest that early surgical intervention may be economically beneficial if surgical intervention is anticipated post-RCT.
- Conference Article
1
- 10.1136/bjsports-2014-094114.94
- Sep 1, 2014
- Abstracts
Introduction Rotator cuff tears are one of the most common musculoskeletal problems affecting the adult population and can cause significant pain and disability. Large tears often require surgical repair but repair failure remains a significant clinical problem with failure rates reported as high as 94%. 4 Hence, there is a growing need for an effective clinical solution. Implanted scaffolds are an increasingly popular option to improve the biomechanical properties and native repair process. Over 20 scaffolds are commercially available and these are derived from mammalian tissue, synthetic polymers or a combination thereof. Despite increasing scaffold use, several concerns regarding their efficacy, safety, biocompatibility and mechanism of action remain. In this in vitro study we have assessed the interactions of human tenocytes from rotator cuff tear patients with 8 commercially available scaffolds. We hypothesise that there will be a difference in cell adhesion and proliferation between the 8 scaffolds. By using diseased human tenocytes, we hypothesise that this in vitro model will more accurately represent human rotator cuff cell response in vivo . In the absence of comparative clinical studies, this model may provide surgeons with information to help them select the most appropriate scaffold for their patients. Methods Tenocytes were extracted from tissue biopsies taken from 2 patients with large-massive rotator cuff tears who were undergoing subacromial decompression surgery. Tenocytes were seeded onto the prepared scaffolds and incubated in supplemented growth media for 28 days. 3 Initial cell attachment was assessed using AlamarBlue ® assay on day 1. Cell proliferation was measured using AlamarBlue ® assay every 3 days over the 28-day period. Results Finely meshed X-Repair and Poly-Tape scaffolds demonstrated the greatest cell attachment at day 1 (p GraftJacket demonstrated statistically increased rate of cell proliferation, particularly during the first 2 weeks. Cell proliferation on all scaffolds was similar after 28 days. Discussion Initial cell attachment was greatest on synthetic scaffolds with straight, regularly oriented, and densely packed fibres. The parallel orientation and dimensions of these synthetic fibres mimic those of native collagen tendon fibres and may account for increased initial cell attachment. Cell proliferation during the first 2 weeks was greatest on non-crosslinked, non-irradiated, human-derived dermis, GraftJacket. These results confirm favourable outcomes from several clinical studies that used GraftJacket to augment rotator cuff repair. 1,2,5 Cell proliferation appeared to be similar on all scaffolds after 28 days, most likely due to cell confluence on the substratum. In terms of biological versus synthetic materials, no clear trend was observed in terms of cell proliferation, but factors such as scaffold structure, collagen source, polymer type and industrial processing techniques could be suggested as possible modulators of cell attachment and growth. References 1 Barber, et al . Arthroscopy . 2012;28:8–15 2 Bond, et al . Arthroscopy . 2008;24:403–409 3 Chard, et al . Ann Rheum Dis . 1987;46:385–390 4 Galatz, et al . J Bone Joint Surg Am . 2004;86:219–224 5 Wong, et al . J Shouler Elbow Surg . 2010;19:104–9
- Research Article
32
- 10.1007/s001130050650
- Nov 2, 2000
- Der Unfallchirurg
Humeral head fractures are commonly found in elderly patients. A high rate of spontaneous rotator cuff tears in this patient group may endanger good results following surgical treatment. 70 patients > 65 years with dislocated humeral head fractures were prospectively studied and treated surgically following a standardised treatment protocol. In all cases the rotator cuff was examined intraoperatively. A tear of the rotator cuff was documented in 4 cases (5%). The prevalence of rotator cuff tears in elderly patients with dislocated humeral head fractures is significantly smaller than expected referring to magnetic resonance-, sonographic and cadaveric studies of same-age patients without fracture. Therefore the rotator cuff may serve as retention anchor for the surgical treatment of dislocated humeral head fractures in elderly patients.