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Bone & Joint Research
Vol. 13, Issue 4 | Pages 169 - 183
15 Apr 2024
Gil-Melgosa L Llombart-Blanco R Extramiana L Lacave I Abizanda G Miranda E Agirre X Prósper F Pineda-Lucena A Pons-Villanueva J Pérez-Ruiz A

Aims. Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells. Methods. HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential. Results. Vorinostat, a HDACi compound, blocked the adipogenic transformation of muscle-associated FAPs in culture, promoting myogenic progression of the satellite cells. Furthermore, it protected muscle from degeneration after acute RC in mice in the earlier muscle degenerative stage after tenotomy. Conclusion. The HDACi vorinostat may be a candidate to prevent early muscular degeneration after RC injury. Cite this article: Bone Joint Res 2024;13(4):169–183


Bone & Joint Research
Vol. 10, Issue 5 | Pages 298 - 306
1 May 2021
Dolkart O Kazum E Rosenthal Y Sher O Morag G Yakobson E Chechik O Maman E

Aims. Rotator cuff (RC) tears are common musculoskeletal injuries which often require surgical intervention. Noninvasive pulsed electromagnetic field (PEMF) devices have been approved for treatment of long-bone fracture nonunions and as an adjunct to lumbar and cervical spine fusion surgery. This study aimed to assess the effect of continuous PEMF on postoperative RC healing in a rat RC repair model. Methods. A total of 30 Wistar rats underwent acute bilateral supraspinatus tear and repair. A miniaturized electromagnetic device (MED) was implanted at the right shoulder and generated focused PEMF therapy. The animals’ left shoulders served as controls. Biomechanical, histological, and bone properties were assessed at three and six weeks. Results. Extension of the tendon from preload to the maximum load to failure was significantly better in the PEMF-treated shoulders at three weeks compared to controls (p = 0.038). The percentage strain was significantly higher in the PEMF group at both timepoints (p = 0.037). Collagen organization was significantly better (p = 0.034) as was tissue mineral density in the PEMF-treated group at three weeks (p = 0.028). Tendon immunohistochemistry revealed a prominent increase in type I collagen at the repair site at three weeks following continuous PEMF treatment compared with controls. None of the other tested parameters differed between the groups. Conclusion. MED-generated PEMF may enhance early postoperative tendon-to-bone healing in an acute rat supraspinatus detachment and repair model. Superior biomechanical elasticity parameters together with better collagen organization suggest improved RC healing. Cite this article: Bone Joint Res 2021;10(5):298–306


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.


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. 1, Issue 7 | Pages 158 - 166
1 Jul 2012
Dean BJF Franklin SL Carr AJ

Introduction. The pathogenesis of rotator cuff disease (RCD) is complex and not fully understood. This systematic review set out to summarise the histological and molecular changes that occur throughout the spectrum of RCD. Methods. We conducted a systematic review of the scientific literature with specific inclusion and exclusion criteria. Results. A total of 101 studies met the inclusion criteria: 92 studies used human subjects exclusively, seven used animal overuse models, and the remaining two studies involved both humans and an animal overuse model. A total of 58 studies analysed supraspinatus tendon exclusively, 16 analysed subacromial bursal tissue exclusively, while the other studies analysed other tissue or varying combinations of tissue types including joint fluid and muscle. The molecular biomarkers that were altered in RCD included matrix substances, growth factors, enzymes and other proteins including certain neuropeptides. Conclusions. The pathogenesis of RCD is being slowly unravelled as a result of the significant recent advances in molecular medicine. Future research aimed at further unlocking these key molecular processes will be pivotal in developing new surgical interventions both in terms of the diagnosis and treatment of RCD


Bone & Joint Research
Vol. 3, Issue 2 | Pages 38 - 47
1 Feb 2014
Hogendoorn S Duijnisveld BJ van Duinen SG Stoel BC van Dijk JG Fibbe WE Nelissen RGHH

Objectives

Traumatic brachial plexus injury causes severe functional impairment of the arm. Elbow flexion is often affected. Nerve surgery or tendon transfers provide the only means to obtain improved elbow flexion. Unfortunately, the functionality of the arm often remains insufficient. Stem cell therapy could potentially improve muscle strength and avoid muscle-tendon transfer. This pilot study assesses the safety and regenerative potential of autologous bone marrow-derived mononuclear cell injection in partially denervated biceps.

Methods

Nine brachial plexus patients with insufficient elbow flexion (i.e., partial denervation) received intramuscular escalating doses of autologous bone marrow-derived mononuclear cells, combined with tendon transfers. Effect parameters included biceps biopsies, motor unit analysis on needle electromyography and computerised muscle tomography, before and after cell therapy.


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.


Objectives

Local corticosteroid infiltration is a common practice of treatment for lateral epicondylitis. In recent studies no statistically significant or clinically relevant results in favour of corticosteroid injections were found. The injection of autologous blood has been reported to be effective for both intermediate and long-term outcomes. It is hypothesised that blood contains growth factors, which induce the healing cascade.

Methods

A total of 60 patients were included in this prospective randomised study: 30 patients received 2 ml autologous blood drawn from contralateral upper limb vein + 1 ml 0.5% bupivacaine, and 30 patients received 2 ml local corticosteroid + 1 ml 0.5% bupivacaine at the lateral epicondyle. Outcome was measured using a pain score and Nirschl staging of lateral epicondylitis. Follow-up was continued for total of six months, with assessment at one week, four weeks, 12 weeks and six months.