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Bone & Joint Research
Vol. 6, Issue 1 | Pages 57 - 65
1 Jan 2017
Gumucio JP Flood MD Bedi A Kramer HF Russell AJ Mendias CL

Objectives. Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics. Methods. Chronic supraspinatus tears were induced in adult rats, and repaired 28 days later. Rats received 0 mg/kg, 3 mg/kg, or 10 mg/kg GSK1120360A daily. Collagen content, contractility, fibre type distribution and size, the expression of genes involved in fibrosis, lipid accumulation, atrophy and inflammation, and the mechanical properties of the enthesis were then assessed two weeks following surgical repair. Results. At two weeks following repair, treatment groups showed increased muscle mass but there was a 15% decrease in force production in the 10 mg/kg group from controls, and no difference between the 0 mg/kg and the 3 mg/kg groups. There was a decrease in the expression of several gene transcripts related to matrix accumulation and fibrosis, and a 50% decrease in collagen content in both treated groups compared with controls. Additionally, the expression of inflammatory genes was reduced in the treated groups compared with controls. Finally, PHD inhibition improved the maximum stress and displacement to failure in repaired tendons. Conclusions. GSK1120360A resulted in improved enthesis mechanics with variable effects on muscle function. PHD inhibition may be beneficial for connective tissue injuries in which muscle atrophy has not occurred. Cite this article: J. P. Gumucio, M. D. Flood, A. Bedi, H. F. Kramer, A. J. Russell, C. L. Mendias. Inhibition of prolyl 4-hydroxylase decreases muscle fibrosis following chronic rotator cuff tear. Bone Joint Res 2017;6:57–65. DOI: 10.1302/2046-3758.61.BJR-2016-0232.R1


Bone & Joint Research
Vol. 3, Issue 9 | Pages 262 - 272
1 Sep 2014
Gumucio J Flood M Harning J Phan A Roche S Lynch E Bedi A Mendias C

Objectives

Rotator cuff tears are among the most common and debilitating upper extremity injuries. Chronic cuff tears result in atrophy and an infiltration of fat into the muscle, a condition commonly referred to as ‘fatty degeneration’. While stem cell therapies hold promise for the treatment of cuff tears, a suitable immunodeficient animal model that could be used to study human or other xenograft-based therapies for the treatment of rotator cuff injuries had not previously been identified.

Methods

A full-thickness, massive supraspinatus and infraspinatus tear was induced in adult T-cell deficient rats. We hypothesised that, compared with controls, 28 days after inducing a tear we would observe a decrease in muscle force production, an accumulation of type IIB fibres, and an upregulation in the expression of genes involved with muscle atrophy, fibrosis and inflammation.


Bone & Joint Research
Vol. 12, Issue 8 | Pages 455 - 466
1 Aug 2023
Zhou H Chen C Hu H Jiang B Yin Y Zhang K Shen M Wu S Wang Z

Aims. Rotator cuff muscle atrophy and fatty infiltration affect the clinical outcomes of rotator cuff tear patients. However, there is no effective treatment for fatty infiltration at this time. High-intensity interval training (HIIT) helps to activate beige adipose tissue. The goal of this study was to test the role of HIIT in improving muscle quality in a rotator cuff tear model via the β3 adrenergic receptor (β3AR). Methods. Three-month-old C57BL/6 J mice underwent a unilateral rotator cuff injury procedure. Mice were forced to run on a treadmill with the HIIT programme during the first to sixth weeks or seventh to 12th weeks after tendon tear surgery. To study the role of β3AR, SR59230A, a selective β3AR antagonist, was administered to mice ten minutes before each exercise through intraperitoneal injection. Supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat were harvested at the end of the 12th week after tendon tear and analyzed biomechanically, histologically, and biochemically. Results. Histological analysis of supraspinatus muscle showed that HIIT improved muscle atrophy, fatty infiltration, and contractile force compared to the no exercise group. In the HIIT groups, supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat showed increased expression of tyrosine hydroxylase and uncoupling protein 1, and upregulated the β3AR thermogenesis pathway. However, the effect of HIIT was not present in mice injected with SR59230A, suggesting that HIIT affected muscles via β3AR. Conclusion. HIIT improved supraspinatus muscle quality and function after rotator cuff tears by activating systemic sympathetic nerve fibre near adipocytes and β3AR. Cite this article: Bone Joint Res 2023;12(8):455–466


Bone & Joint Research
Vol. 8, Issue 3 | Pages 118 - 125
1 Mar 2019
Doi N Izaki T Miyake S Shibata T Ishimatsu T Shibata Y Yamamoto T

Objectives. Indocyanine green (ICG) fluorescence angiography is an emerging technique that can provide detailed anatomical information during surgery. The purpose of this study is to determine whether ICG fluorescence angiography can be used to evaluate the blood flow of the rotator cuff tendon in the clinical setting. Methods. Twenty-six patients were evaluated from October 2016 to December 2017. The participants were categorized into three groups based on their diagnoses: the rotator cuff tear group; normal rotator cuff group; and adhesive capsulitis group. After establishing a posterior standard viewing portal, intravenous administration of ICG at 0.2 mg/kg body weight was performed, and fluorescence images were recorded. The time from injection of the drug to the beginning of enhancement of the observed area was measured. The hypovascular area in the rotator cuff was evaluated, and the ratio of the hypovascular area to the anterolateral area of the rotator cuff tendon was calculated (hypovascular area ratio). Results. ICG fluorescence angiography allowed for visualization of blood flow in the rotator cuff in all groups. The adhesive capsulitis group showed significantly earlier enhancement than the other groups. Furthermore, the adhesive capsulitis group had a significantly smaller hypovascular area ratio than the other groups. Conclusion. ICG fluorescence angiography allowed for evaluation of real-time blood flow of the rotator cuff in arthroscopic shoulder surgery. The techniques of ICG fluorescence angiography are simple and easy to observe, observer reliability is high, and it has utility for evaluating blood flow during surgery. Cite this article: N. Doi, T. Izaki, S. Miyake, T. Shibata, T. Ishimatsu, Y. Shibata, T. Yamamoto. Intraoperative evaluation of blood flow for soft tissues in orthopaedic surgery using indocyanine green fluorescence angiography: A pilot study. Bone Joint Res 2019;8:118–125. DOI: 10.1302/2046-3758.83.BJR-2018-0151.R1


Bone & Joint Research
Vol. 3, Issue 5 | Pages 155 - 160
1 May 2014
Carr AJ Rees JL Ramsay CR Fitzpatrick R Gray A Moser J Dawson J Bruhn H Cooper CD Beard DJ Campbell MK

This protocol describes a pragmatic multicentre randomised controlled trial (RCT) to assess the clinical and cost effectiveness of arthroscopic and open surgery in the management of rotator cuff tears. This trial began in 2007 and was modified in 2010, with the removal of a non-operative arm due to high rates of early crossover to surgery. . Cite this article: Bone Joint Res 2014;3:155–60


Bone & Joint Research
Vol. 2, Issue 7 | Pages 122 - 128
1 Jul 2013
Mukovozov I Byun S Farrokhyar F Wong I

Aims. We performed a systematic review of the literature to determine whether earlier surgical repair of acute rotator cuff tear (ARCT) leads to superior post-operative clinical outcomes. Methods. The MEDLINE, Embase, CINAHL, Web of Science, Cochrane Libraries, controlled-trials.com and clinicaltrials.gov databases were searched using the terms: ‘rotator cuff’, or ‘supraspinatus’, or ‘infraspinatus’, or ‘teres minor’, or ‘subscapularis’ AND ‘surgery’ or ‘repair’. This gave a total of 15 833 articles. After deletion of duplicates and the review of abstracts and full texts by two independent assessors, 15 studies reporting time to surgery for ARCT repair were included. Studies were grouped based on time to surgery < 3 months (group A, seven studies), or > 3 months (group B, eight studies). Weighted means were calculated and compared using Student’s t-test. . Results. Group B had a significantly higher pre-operative Constant score (CS) (p < 0.001), range of movement in external rotation (p = 0.003) and abduction (p < 0.001) compared with group A. Both groups showed clinical improvement with surgical repair; group A had a significantly improved Constant score, University of California, Los Angeles (UCLA) shoulder score, abduction and elevation post-operatively (all p < 0.001). Group B had significantly improved Constant score (p < 0.001) and external rotation (p < 0.001) post-operatively. The mean Constant score improved by 33.5 for group A and by 27.5 for group B. Conclusion. These findings should be interpreted with caution due to limitations and bias inherent to case-series. We suggest a trend that earlier time to surgery may be linked to better Constant score, and active range of movement in abduction and elevation. Additional prospective studies are required


Bone & Joint Research
Vol. 12, Issue 3 | Pages 179 - 188
7 Mar 2023
Itoh M Itou J Imai S Okazaki K Iwasaki K

Aims

Orthopaedic surgery requires grafts with sufficient mechanical strength. For this purpose, decellularized tissue is an available option that lacks the complications of autologous tissue. However, it is not widely used in orthopaedic surgeries. This study investigated clinical trials of the use of decellularized tissue grafts in orthopaedic surgery.

Methods

Using the ClinicalTrials.gov (CTG) and the International Clinical Trials Registry Platform (ICTRP) databases, we comprehensively surveyed clinical trials of decellularized tissue use in orthopaedic surgeries registered before 1 September 2022. We evaluated the clinical results, tissue processing methods, and commercial availability of the identified products using academic literature databases and manufacturers’ websites.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 596 - 610
21 Oct 2024
Toegel S Martelanz L Alphonsus J Hirtler L Gruebl-Barabas R Cezanne M Rothbauer M Heuberer P Windhager R Pauzenberger L

Aims

This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated.

Methods

Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA).


Bone & Joint Research
Vol. 13, Issue 9 | Pages 474 - 484
10 Sep 2024
Liu Y Li X Jiang L Ma J

Aims

Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration.

Methods

Linear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 165 - 177
1 Mar 2023
Boyer P Burns D Whyne C

Aims

An objective technological solution for tracking adherence to at-home shoulder physiotherapy is important for improving patient engagement and rehabilitation outcomes, but remains a significant challenge. The aim of this research was to evaluate performance of machine-learning (ML) methodologies for detecting and classifying inertial data collected during in-clinic and at-home shoulder physiotherapy exercise.

Methods

A smartwatch was used to collect inertial data from 42 patients performing shoulder physiotherapy exercises for rotator cuff injuries in both in-clinic and at-home settings. A two-stage ML approach was used to detect out-of-distribution (OOD) data (to remove non-exercise data) and subsequently for classification of exercises. We evaluated the performance impact of grouping exercises by motion type, inclusion of non-exercise data for algorithm training, and a patient-specific approach to exercise classification. Algorithm performance was evaluated using both in-clinic and at-home data.


Bone & Joint Research
Vol. 9, Issue 6 | Pages 285 - 292
1 Jun 2020
Wang Z Li H Long Z Lin S Thoreson AR Moran SL Gingery A Amadio PC Steinmann SP Zhao C

Aims

Many biomechanical studies have shown that the weakest biomechanical point of a rotator cuff repair is the suture-tendon interface at the medial row. We developed a novel double rip-stop (DRS) technique to enhance the strength at the medial row for rotator cuff repair. The objective of this study was to evaluate the biomechanical properties of the DRS technique with the conventional suture-bridge (SB) technique and to evaluate the biomechanical performance of the DRS technique with medial row knots.

Methods

A total of 24 fresh-frozen porcine shoulders were used. The infraspinatus tendons were sharply dissected and randomly repaired by one of three techniques: SB repair (SB group), DRS repair (DRS group), and DRS with medial row knots repair (DRSK group). Specimens were tested to failure. In addition, 3 mm gap formation was measured and ultimate failure load, stiffness, and failure modes were recorded.


Bone & Joint Research
Vol. 9, Issue 1 | Pages 23 - 28
1 Jan 2020
Kurosawa T Mifune Y Inui A Nishimoto H Ueda Y Kataoka T Yamaura K Mukohara S Kuroda R

Aims

The purpose of this study was to evaluate the in vitro effects of apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase (NOX) and a downregulator of intracellular reactive oxygen species (ROS), on high glucose-induced oxidative stress on tenocytes.

Methods

Tenocytes from normal Sprague-Dawley rats were cultured in both control and high-glucose conditions. Apocynin was added at cell seeding, dividing the tenocytes into four groups: the control group; regular glucose with apocynin (RG apo+); high glucose with apocynin (HG apo+); and high glucose without apocynin (HG apo–). Reactive oxygen species production, cell proliferation, apoptosis and messenger RNA (mRNA) expression of NOX1 and 4, and interleukin-6 (IL-6) were determined in vitro.


Objectives

Platelet-rich fibrin matrix (PRFM) has been proved to enhance tenocyte proliferation but has mixed results when used during rotator cuff repair. The optimal PRFM preparation protocol should be determined before clinical application. To screen the best PRFM to each individual’s tenocytes effectively, small-diameter culture wells should be used to increase variables. The gelling effect of PRFM will occur when small-diameter culture wells are used. A co-culture device should be designed to avoid this effect.

Methods

Tenocytes harvested during rotator cuff repair and blood from a healthy volunteer were used. Tenocytes were seeded in 96-, 24-, 12-, and six-well plates and co-culture devices. Appropriate volumes of PRFM, according to the surface area of each culture well, were treated with tenocytes for seven days. The co-culture device was designed to avoid the gelling effect that occurred in the small-diameter culture well. Cell proliferation was analyzed by water soluble tetrazolium-1 (WST-1) bioassay.


Bone & Joint Research
Vol. 3, Issue 8 | Pages 252 - 261
1 Aug 2014
Tilley JMR Murphy RJ Chaudhury S Czernuszka JT Carr AJ

Objectives

The effects of disease progression and common tendinopathy treatments on the tissue characteristics of human rotator cuff tendons have not previously been evaluated in detail owing to a lack of suitable sampling techniques. This study evaluated the structural characteristics of torn human supraspinatus tendons across the full disease spectrum, and the short-term effects of subacromial corticosteroid injections (SCIs) and subacromial decompression (SAD) surgery on these structural characteristics.

Methods

Samples were collected inter-operatively from supraspinatus tendons containing small, medium, large and massive full thickness tears (n = 33). Using a novel minimally invasive biopsy technique, paired samples were also collected from supraspinatus tendons containing partial thickness tears either before and seven weeks after subacromial SCI (n = 11), or before and seven weeks after SAD surgery (n = 14). Macroscopically normal subscapularis tendons of older patients (n = 5, mean age = 74.6 years) and supraspinatus tendons of younger patients (n = 16, mean age = 23.3) served as controls. Ultra- and micro-structural characteristics were assessed using atomic force microscopy and polarised light microscopy respectively.


Bone & Joint Research
Vol. 5, Issue 6 | Pages 269 - 275
1 Jun 2016
Ono Y Woodmass JM Nelson AA Boorman RS Thornton GM Lo IKY

Objectives

This study evaluated the mechanical performance, under low-load cyclic loading, of two different knotless suture anchor designs: sutures completely internal to the anchor body (SpeedScrew) and sutures external to the anchor body and adjacent to bone (MultiFIX P).

Methods

Using standard suture loops pulled in-line with the rotator cuff (approximately 60°), anchors were tested in cadaveric bone and foam blocks representing normal to osteopenic bone. Mechanical testing included preloading to 10 N and cyclic loading for 500 cycles from 10 N to 60 N at 60 mm/min. The parameters evaluated were initial displacement, cyclic displacement and number of cycles and load at 3 mm displacement relative to preload. Video recording throughout testing documented the predominant source of suture displacement and the distance of ‘suture cutting through bone’.


Bone & Joint Research
Vol. 3, Issue 6 | Pages 193 - 202
1 Jun 2014
Hast MW Zuskov A Soslowsky LJ

Tendinopathy is a debilitating musculoskeletal condition which can cause significant pain and lead to complete rupture of the tendon, which often requires surgical repair. Due in part to the large spectrum of tendon pathologies, these disorders continue to be a clinical challenge. Animal models are often used in this field of research as they offer an attractive framework to examine the cascade of processes that occur throughout both tendon pathology and repair. This review discusses the structural, mechanical, and biological changes that occur throughout tendon pathology in animal models, as well as strategies for the improvement of tendon healing.

Cite this article: Bone Joint Res 2014;3:193–202.


Bone & Joint Research
Vol. 7, Issue 5 | Pages 362 - 372
1 May 2018
Ueda Y Inui A Mifune Y Sakata R Muto T Harada Y Takase F Kataoka T Kokubu T Kuroda R

Objectives

The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy.

Methods

Using tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours in vitro. In an in vivo study, using diabetic rats and controls, NOX1 and 4 expressions in Achilles tendon were also determined.


Bone & Joint Research
Vol. 3, Issue 4 | Pages 117 - 122
1 Apr 2014
Uhthoff HK Coletta E Trudel G

Objectives

Although many clinical and experimental investigations have shed light on muscle atrophy and intramuscular accumulation of fat after rotator cuff disruption, none have reported on their onset in the absence of muscle retraction.

Methods

In 30 rabbits, we detached one supraspinatus (SSP) tendon and repaired it immediately, thus preventing muscle retraction. The animals were killed in groups of 10 at one, two and six weeks. Both shoulders of 15 non-operated rabbits served as controls. We measured the weight and volume of SSP muscles and quantified the cross-sectional area of intramuscular fat (i-fat) histologically.


Bone & Joint Research
Vol. 5, Issue 12 | Pages 602 - 609
1 Dec 2016
Muto T Kokubu T Mifune Y Inui A Sakata R Harada Y Takase F Kurosaka M

Objectives

Triamcinolone acetonide (TA) is widely used for the treatment of rotator cuff injury because of its anti-inflammatory properties. However, TA can also produce deleterious effects such as tendon degeneration or rupture. These harmful effects could be prevented by the addition of platelet-rich plasma (PRP), however, the anti-inflammatory and anti-degenerative effects of the combined use of TA and PRP have not yet been made clear. The objective of this study was to determine how the combination of TA and PRP might influence the inflammation and degeneration of the rotator cuff by examining rotator cuff-derived cells induced by interleukin (IL)-1ß.

Methods

Rotator cuff-derived cells were seeded under inflammatory stimulation conditions (with serum-free medium with 1 ng/ml IL-1ß for three hours), and then cultured in different media: serum-free (control group), serum-free + TA (0.1mg/ml) (TA group), serum-free + 10% PRP (PRP group), and serum-free + TA (0.1mg/ml) + 10% PRP (TA+PRP group). Cell morphology, cell viability, and expression of inflammatory and degenerative mediators were assessed.


Bone & Joint Research
Vol. 1, Issue 9 | Pages 210 - 217
1 Sep 2012
Walton JR Murrell GAC

Objectives

The aim of this study was to determine whether there is any significant difference in temporal measurements of pain, function and rates of re-tear for arthroscopic rotator cuff repair (RCR) patients compared with those patients undergoing open RCR.

Methods

This study compared questionnaire- and clinical examination-based outcomes over two years or longer for two series of patients who met the inclusion criteria: 200 open RCR and 200 arthroscopic RCR patients. All surgery was performed by a single surgeon.