The Role of Indian Hedgehog Signaling in Tendon Response to Subacromial Impingement: Evaluation Using a Mouse Model

2021 ◽  
pp. 036354652110622
Author(s):  
Yulei Liu ◽  
Xiang-Hua Deng ◽  
Xueying Zhang ◽  
Ting Cong ◽  
Daoyun Chen ◽  
...  

Background: The underlying cellular and molecular mechanisms involved in the development of tendinopathy due to subacromial supraspinatus tendon (SST) impingement and the response to subsequent removal of impingement remain unknown. Purpose: To investigate the involvement of Indian hedgehog (IHH) signaling in the development of SST tendinopathy and the subsequent healing process after the relief of subacromial impingement in a novel mouse shoulder impingement model. Study Design: Controlled laboratory study. Methods: A total of 48 male wild-type C57BL/6 mice were used in this study. Supraspinatus tendinopathy was induced by inserting a microsurgical clip into the subacromial space bilaterally. Eleven mice were sacrificed at 4 weeks after surgery to establish impingement baseline; 24 mice underwent clip removal at 4 weeks after surgery and then were euthanized at 2 or 4 weeks after clip removal. Thirteen mice without surgical intervention were utilized as the control group. All SSTs were evaluated with biomechanical testing; quantitative histomorphometry after staining with hematoxylin and eosin, Alcian blue, and picrosirius red; and immunohistochemical staining (factor VIII, IHH, Patched1 [PTCH1], and glioma-associated oncogene homolog 1 [GLI1]). Results: The mean failure force and stiffness in the 4-week impingement group decreased significantly compared with the control group ( P < .001) and gradually increased at 2 and 4 weeks after clip removal. Histological analysis demonstrated increased cellularity and disorganized collagen fibers in the SST, with higher modified Bonar scores at 4 weeks, followed by gradual improvement after clip removal. The IHH-positive area and PTCH1- and GLI1-positive cell percentages significantly increased after 4 weeks of clip impingement (20.64% vs 2.06%, P < .001; 53.9% vs 28.03%, P = .016; and 30% vs 12.19%, P = .036, respectively) and continuously increased after clip removal. Conclusion: The authors’ findings suggest that the hedgehog signaling pathway and its downstream signaling mediator and target GLI1 may play a role in the development and healing process of rotator cuff tendinopathy due to extrinsic rotator cuff impingement. Clinical Relevance: This study suggests the potential for the hedgehog pathway, together with its downstream targets, as candidates for further study as potential therapeutic targets in the treatment of supraspinatus tendinopathy.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Aneta Bac ◽  
Magdalena Wróbel ◽  
Katarzyna Ogrodzka-Ciechanowicz ◽  
Edyta Michalik ◽  
Anna Ścisłowska-Czarnecka

Abstract The assessment of the six-week influence of Kinesio Taping combined with a rehabilitation on selected ultrasonography measurements, the level of disability, and the quality of life in patients with rotator cuff lesions. 60 participants were randomly assigned into a taping group (KT combined with a six-week rehabilitating protocol) and a control group (only rehabilitation protocol). In all patients the following assessments were performed twice: USG, UEFI and NHP questionnaires. In the examination of the subacromial space and the subacromial bursa in the taping group, no statistical significance was observed. A statistically significant change in the thickness of the muscles was obtained only for the thickness of the infraspinatus in the taping group. A statistically significant change was obtained in the assessment of tendinopathy only for the supraspinatus muscle in both groups. Within both groups a statistically significant difference was observed in the average UEFI and NHP scores; however, the differences in the scores obtained between the groups were not statistically significant. The use of KT with a rehabilitation program did not yield statistically significantly better results in the improvement of selected shoulder region indicators, the function of the upper limb and the quality of life.


2020 ◽  
Vol 48 (3) ◽  
pp. 706-714 ◽  
Author(s):  
Yucheng Sun ◽  
Jae-Man Kwak ◽  
Erica Kholinne ◽  
Youlang Zhou ◽  
Jun Tan ◽  
...  

Background: Microfracture of the greater tuberosity has been proved effective for enhancing tendon-to-bone healing after rotator cuff repair. However, no standard diameter for the microfracture has been established. Purpose/Hypothesis: This study aimed to assess treatment with large- and small-diameter microfractures to enhance healing during rotator cuff repair surgery in a rabbit model of chronic rotator cuff tear. It was hypothesized that a small-diameter microfracture had advantages in terms of tendon-to-bone integration, bone-tendon interface maturity, microfracture healing, and biomechanical properties compared with a large-diameter microfracture. Study Design: Controlled laboratory study. Methods: Bilateral supraspinatus tenotomy from the greater tuberosity was performed on 21 New Zealand White rabbits. Bilateral supraspinatus repair was performed 6 weeks later. Small-diameter (0.5 mm) microfracture and large-diameter microfracture (1 mm) were performed on the left side and right side, respectively, in 14 rabbits as a study group, and simple repair without microfracture was performed in 7 rabbits as a control group. At 12 weeks later, 7 of 14 rabbits in the study group were sacrificed for micro–computed tomography evaluation and biomechanical testing. Another 6 rabbits were sacrificed for histological evaluation. In the control group, 3 of the 7 rabbits were sacrificed for histological evaluation and the remaining rabbits were sacrificed for biomechanical testing. Results: Significantly better bone-to-tendon integration was observed in the small-diameter microfracture group. Better histological formation and maturity of the bone-tendon interface corresponding to better biomechanical results (maximum load to failure and stiffness) were obtained on the small-diameter microfracture side compared with the large-diameter side and the control group. The large-diameter microfracture showed worse radiographic and histological properties for healing of the microfracture holes on the greater tuberosity. Additionally, the large-diameter microfracture showed inferior biomechanical properties but similar histological results compared with the control group. Conclusion: Small-diameter microfracture showed advantages with enhanced rotator cuff healing for biomechanical, histological, and radiographic outcomes compared with large-diameter microfracture, and large-diameter microfracture may worsen the rotator cuff healing. Clinical Relevance: This animal study suggested that a smaller diameter microfracture may be a better choice to enhance healing in clinical rotator cuff repair surgery in humans.


2020 ◽  
Vol 48 (9) ◽  
pp. 2161-2169
Author(s):  
Dong Min Kim ◽  
In Kyoung Shim ◽  
Myung Jin Shin ◽  
Jae Hee Choi ◽  
Yu Na Lee ◽  
...  

Background: Tearing and degeneration of the rotator cuff at the tendon-to-bone junction are common in adults aged ≥50 years. Few studies have reported on the relationship between estrogen and the rotator cuff enthesis. In addition to preventing bone loss, selective estrogen receptor modulators have been shown to improve tendon and muscle quality. Purpose: To evaluate the effects of raloxifene (RLX) and vitamin D on rotator cuff tendon-to-bone healing in a rat model. Study Design: Controlled laboratory study. Methods: A total of 29 female rats (58 shoulders) were assigned to 4 groups: (1) control group, (2) ovariectomy (OVX)–only group, (3) no RLX group (OVX and rotator cuff repair [RCR]), and (4) RLX group (OVX, RCR, and RLX). Rats that did not undergo rotator cuff tear (RCT) surgery were divided into the control and OVX-only groups according to OVX surgery. Rats that underwent RCT surgery and RCR were divided into the no RLX and RLX groups according to RLX and vitamin D administration. An estrogen-deficient state was induced by OVX at 12 weeks of age. Bone mineral density (BMD) and trabecular bone characteristics were measured by micro–computed tomography, and healing of the tendon-to-bone junction was evaluated by biomechanical testing, histomorphometry, and micro–magnetic resonance imaging (MRI). Results: The mean final body weight (BW; 461.6 ± 47.3 g) of the OVX-only group was significantly higher and BMD (0.25 ± 0.07 g/cm3) was significantly lower ( P < .001) than the mean final BW (338.5 ± 35.1 g) and BMD (0.48 ± 0.05 g/cm3) of the control group. In contrast, the RLX group showed that the BW (369.6 ± 35.8 g) and BMD (0.41 ± 0.08 g/cm3) were not significantly different from the control group. The RLX group had a significantly higher histomorphometric total score (8.50 ± 1.05) than the no RLX group (4.83 ± 2.48). On biomechanical testing, the RLX group (29.7 ± 9.1 N) showed a significantly higher load to failure than the no RLX group (19.4 ± 8.8 N). On micro-MRI, the RLX group had a more homogeneous low signal and tendon continuity than the no RLX group. Conclusion: The combination treatment of RLX and vitamin D prevented a decrease in local BMD (greater tuberosity of the proximal humerus) and enhanced tendon-to-bone healing of the rotator cuff in a rat model. Clinical Relevance: This study induced an estrogen-deficient state similar to the human postmenopausal state and used drugs that are actually being prescribed in a clinical situation.


2009 ◽  
Vol 91 (5) ◽  
pp. 414-416 ◽  
Author(s):  
M Bhatia ◽  
B Singh ◽  
N Nicolaou ◽  
KJ Ravikumar

INTRODUCTION Concern exists regarding potential damage to the rotator cuff from repeated corticosteroid injections into the subacromial space. PATIENTS AND METHODS In this retrospective, case-controlled study, 230 consecutive patients presenting to three orthopaedic units with subacromial impingement and investigated as an end-point with magnetic resonance imaging (MRI) of the shoulder were divided into groups having received less than three or three or more subacromial injections of corticosteroids. RESULTS With no significant difference in age and sex distribution, analysis by MRI showed no significant difference between the two groups in the incidence of rotator cuff tear (P < 1.0). CONCLUSIONS This suggests that corticosteroid use in patients with subacromial impingement should not be considered a causative factor in rotator cuff tears.


2019 ◽  
Vol 27 (2) ◽  
pp. 230949901985638
Author(s):  
Ahmet Oztermeli ◽  
Sinan Karaca ◽  
Istemi Yucel ◽  
Ahmet Midi ◽  
Elif Itir Sen ◽  
...  

Objectives:The aim of this study was to determine whether erythropoietin (EPO) can enhance rotator cuff healing in rats as measured by histological analysis and biomechanical testing.Methods:A total of 72 rats were included in this study. In the control group ( n = 24), repair was performed without EPO injection. In the local group ( n = 24) EPO was injected in the repair site. In the systemic group ( n = 24) EPO was administered as an intraperitoneal injection every day for 10 days after repair. Rats were euthanized on day 10 ( n = 12 from each group) and day 28 ( n = 12 from each group). Histopathological ( n = 6) and biomechanical examinations ( n = 6) were done.Results:Biomechanical results reveal that the maximum load to failure values of the early control group were statistically lower than those of the early systemic group ( p = 0.006). Comparing the the total Bonar values histopathologically reveal that the early systemic group was statistically higher than those of the early local group ( p = 0.043). The late control group was statistically higher than those of the late local group ( p = 0.003) and the late systemic group ( p = 0.034). The late systemic group was statistically higher than those of the late local group ( p = 0.003).Conclusions:EPO application had a positive effect biomechanically in the early euthanized group and histopathologically in the late euthanized group.


2017 ◽  
Vol 26 (4) ◽  
pp. 580-588 ◽  
Author(s):  
Jian-Chun Zong ◽  
Michael J. Mosca ◽  
Ryan M. Degen ◽  
Amir Lebaschi ◽  
Camila Carballo ◽  
...  

2017 ◽  
Vol 25 (1) ◽  
pp. 230949901769032 ◽  
Author(s):  
Carlos Torrens ◽  
Eduard Alentorn-Geli ◽  
Juan Francisco Sanchez ◽  
Anna Isart ◽  
Fernando Santana

Purpose: Coracoid morphology has been related to coracoid impingement mainly resulting in anterior shoulder pain aggravated by forward flexion and internal rotation. However, the coracoid process morphology can also affect the inclination of the coracoacromial ligament and subsequently the subacromial space in the same way that acromial slope does. The purpose of this study was to evaluate the influence of the coracoid body–glenoid surface, coracoid tip–glenoid surface, and coracoid body–coracoid tip angles (coracoid inclination angles) on rotator cuff tears (RCTs). Methods: Fifty patients with documented RCT and 50 patients with normal rotator cuff (control) were included. The coracoid inclination angles were determined in both groups by measuring on computed tomography scans the angle created by the coracoid body and the glenoid surface (A1), the angle created by the coracoid tip and the glenoid surface (A2), and the angle created by the coracoid body and the coracoid tip (A3). Results: All angles were significantly lower in the RCT group compared to the control group: mean A1 angle of 49.7° and 54.61°, respectively ( p = 0.011); mean A2 angle of 76.45° and 93.6°, respectively ( p < 0.001); and mean A3 angle of 132.33° and 144.34°, respectively ( p < 0.001). Conclusions: Decreased coracoid body–glenoid surface, coracoid tip–glenoid surface, and coracoid body–coracoid tip angles are associated with RCT. Decreased angles may reduce subacromial space by projecting the coracoacromial ligament more vertically.


2012 ◽  
Vol 42 (5) ◽  
pp. 400-412 ◽  
Author(s):  
Amee L. Seitz ◽  
Philip W. McClure ◽  
Sheryl Finucane ◽  
Jessica M. Ketchum ◽  
Matthew K. Walsworth ◽  
...  

2019 ◽  
Vol 1 ◽  
pp. 2-6
Author(s):  
Asad Naqvi ◽  
Timothy Ariyanayagam ◽  
Mir Akber Ali ◽  
Akhila Rachakonda ◽  
Hema N. Choudur

Objective: The objective of this study was to outline a novel unique concept of secondary impingement of the muscles, myotendons, and tendons of the rotator cuff from hypertrophy as a result of strength training exercises. Methods: In this retrospective observational study, 58 patients were referred for an magnetic resonance imaging (MRI) by the orthopedic surgeon to the radiology department over a period of 1½ years. All patients gave a history of strength training exercises and presented with clinical features of rotator cuff impingement. Results: We identified features of hypertrophy of rotator cuff muscles, myotendons, and tendons in 12 of these 58 patients. This was the only abnormality on MRI. The hypertrophy of rotator cuff muscles and tendon bulk completely filling the subacromial space to the point of overfilling and resulting in secondary compressive features. Conclusion: Rotator cuff impingement is a common phenomenon that can occur with various inlet and outlet pathological conditions. However, rotator cuff impingement may also result from muscle and tendon hypertrophy from strength training regimens. Hypertrophy of the rotator cuff can result in overfilling of the subacromial space, leading to secondary impingement, which we have termed as “pseudo-impingement.”


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Gabriela Elis Wachholz ◽  
Julia do Amaral Gomes ◽  
Juliano André Boquett ◽  
Fernanda Sales Luiz Vianna ◽  
Lavínia Schuler-Faccini ◽  
...  

Abstract Background Due to the diversity of studies in animal models reporting that molecular mechanisms are involved in the teratogenic effect of the Zika virus (ZIKV), the objective of the present study is to evaluate the methodological quality of these studies, as well as to demonstrate which genes and which molecular pathways are affected by ZIKV in different animal models. Methods This search will be performed in four databases: PubMed/MEDLINE, EMBASE, Web of Science, and Scopus, as well as in the grey literature. The studies selection process will be reported through the PRISMA Statement diagram model. All studies describing the molecular mechanisms possibly involved in the development of malformations caused by embryonic/fetal ZIKV exposure in animal models with an appropriate control group and methodology will be included (including, for instance, randomized and non-randomized studies). All animals used as experimental models for ZIKV teratogenesis may be included as long as exposure to the virus occurred during the embryonic/fetal period. From the selected studies, data will be extracted using a previously prepared standard form. Bias risk evaluation will be conducted following the SYRCLE’s Risk of Bias tool. All data obtained will be tabulated and organized by outcomes (morphological and molecular). Discussion With the proposed systematic review, we expect to present results about the methodological quality of the published studies with animal models that investigated the molecular mechanisms involved in the teratogenic effect of ZIKV, as well as to show the studies with greater reliability. Systematic review registration PROSPERO CRD42019157316


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