R Appleyard, Murray Maxwell Biomechanics Lab, Royal North Shore Hospital, Sydney. The fundamental mechanisms that underlie tendon breakdown are ill understood. There is an emerging hypothesis that altered mechanical strain modulates the metabolism and/or phenotype of tenocytes, disrupting the balance of matrix synthesis and degradation, and that rupture then occurs through an abnormal tendon matrix. The critically regulated genes have not yet been determined. We have developed sheep model in sheep where both stress-deprived and over-stressed areas can be examined in the one tendon, to evaluate the pathological and molecular changes over time. We have also used ‘wild type’ and genetically modified mice to determine the role of specific enzymes and proteoglycans in
Coblation is supposed to enhance healing due to increasing vascularity in the degenerated tendon. In the present study the effect of coblation treatment on
Aims. Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related
Introduction. We previously reported that disruption of TGFβ signaling in limb mesenchyme resulted in complete failure of tendon differentiation. Materials and Methods. To bypass this early function and study additional roles of TGFβ signaling in tendon development we disrupted TGFβ signaling in tenocytes after they assumed the tendon cell fate by using the tendon deletor ScxCre to target the floxed type2 TGFβ receptor. Results. Most mutant (Tgfbr2;ScxCre) pups appeared normal at birth but exhibited movement difficulties and splayed limbs by P3. ScxGFP signal revealed that tendon formation was not affected in CKO embryos. Nonetheless, three distinct tendon phenotypes were manifested later in development: (a) a single flexor tendon consistently snapped at late embryonic stage; whereas at post-natal stage, some tendons that appeared intact at birth were (b) eventually eliminated or (c) retained structural integrity with a substantial loss of the ScxGFP signal. Interestingly, the ScxGFP-negative cells also lost other tendon marker genes. Lineage tracing revealed that these cells were derived from Scx-expressing cells, suggesting a disruption of the tendon cell fate (dedifferentiation) but we found no evidence of transdifferentiation. Varying degrees of
Depletion of Scleraxis-lineage (ScxLin) cells in adult tendon recapitulates age-related decrements in cell density, ECM organization and composition. However, depletion of ScxLin cells improves tendon healing, relative to age-matched wildtype mice, while aging impairs healing. Therefore, we examined whether ScxLin depletion and aging result in comparable shifts in the tendon cell environment and defined the intrinsic programmatic shifts that occur with natural aging, to define the key regulators of age-related healing deficits. ScxLin cells were depleted in 3M-old Scx-Cre+; Rosa-DTRF/+ mice via diphtheria toxin injections into the hindpaw. Rosa-DTRF/+ mice were used as wildtype (WT) controls. Tendons were harvested from 6M-old ScxLin depleted and WT mice, and 21-month-old (21M) C57Bl/6 mice (aged). FDL tendons (n=6) were harvested for single-cell RNAseq, pooled, collagenase digested, and sorted for single cell capture. Data was processed using Cell Ranger and then aligned to the annotated mouse genome (mm10). Filtering, unsupervised cell clustering, and differential gene expression (DEG) analysis were performed using Seurat. Following integration and sub-clustering of the tenocyte populations, five distinct subpopulations were observed. In both ScxLin depletion and aging, ‘ECM synthesizers’ and ‘ECM organizers’ populations were lost, consistent with disruptions in tissue homeostasis and altered ECM composition. However, in ScxLin depleted mice retention of a ‘specialized ECM remodeler’ population was observed, while aging tendon cells demonstrated inflammatory skewing with retention of a ‘pro-inflammatory tenocyte population’. In addition, enrichment of genes associated with protein misfolding clearance were observed in aged tenocytes. Finally, a similar inflammatory skewing was observed in aged tendon-resident macrophages, with this skewing not observed in ScxLin depleted tendons. These data suggest that loss of ‘ECM synthesizer’ populations underpins disruptions in tendon homeostasis. However, retention of ‘specialized remodelers’ promotes enhanced healing (ScxLin depletion), while inflammatory skewing may drive the impaired healing response in aged tendons.
There is a growing socio-economic need (i.e. “ageing society”) for effective and reproducible strategies to repair musculoskeletal tissue. In particular, acute tendon injury and chronic tendinopathies remain clinically challenging and novel treatment modalities are urgently needed. Tendons resemble a connective tissue rich in highly organized collagen fibers, displaying a remarkably high tensile strength. However, partly due to the low number of cells and their more or less avascular nature tendons heal relatively slowly. Ultimately, tendon regeneration encompasses the full restoration of the biological, biochemical and biomechanical properties, which are often impaired by endogenous healing cascades. Usually, a connective scar tissue forms at the injury site and the replaced tissue does not function adequately at high strain levels, increasing the chance of re-rupture. Despite significant advancements in tissue regeneration and engineering strategies, the clinical impact for the regeneration of tendon remains limited. For the development of novel methods to repair tendons we need to pin down the molecular and cellular mechanisms amenable to modulate endogenous (or exogenous) cell behaviour towards functional tissue regeneration. By comparing the gene expression profile of Achilles tendon tissue harvested from young-mature and old mice we demonstrate profound changes in the expression of ECM-related proteins and a previously unknown role of Secreted protein acidic and rich in cysteine (Sparc; also known as BM-40 or osteonectin) in tendons. Sparc levels in tendons are critical for proper collagen fibril maturation and its age-related decrease, together with a change in ECM properties potentially drives adipogenic differentiation of tendon stem and progenitor cells (TDSPCs) and consequently lipid accretion in tendons. Generally, the fate of stem/ progenitor cells is largely determined by stimuli from the stem cell niche. In tendons, we describe a novel cellular barrier, most likely preventing the leakage of blood-borne products into the tendon proper. We propose that this “blood-tendon barrier” is part of the stem cell niche in tendons controlling TDSCP fate, preventing erroneous differentiation. By investigating the developmental programs driving tendon tissue formation and on the other hand the mechanisms contributing to the senescence of tendons, ultimately resulting in decreased quality of tendons in the elderly, novel targets for clinical intervention potentially can be discovered.
Tendon and ligament tissues are fascinating in their simplistic appearance of tissue architecture coupled with outstanding biomechanical properties. In the last decade, the mechanisms governing their development, degenerative disease progression and step-wise repair process are becoming better understood. In this talk, I will present an overview of our basic research work on these following points. (i) Tendon generation: I will discuss our finding on the role of growth and biomechanical factors influencing tendon stem/progenitor cells; (ii)
Patellar tendinosis (PT) is common and can result in prolonged disability, especially in jumping athletes. Recently developed ultra-short-echo (UTE) MRI sequences allow for quantitative evaluation of tendon biostructure with T2* relaxometry. This study evaluated the relationships between changes over time (COT) in quantitative T2*-metrics, qualitative PT grades, and patient reported symptoms within 10 male basketball players from a single collegiate basketball team. All subjects completed weekly VISA-P symptomology questionnaires over the basketball season. Bilateral 3-Tesla MRIs (GE Healthcare) were obtained at pre- and post-season study visits. High-resolution, PD-weighted, FSE sequences were used to qualitatively grade PT. Quantitative T2*-metrics were evaluated using high-resolution, 3D, multi-echo, UTE-MRI sequences. Bilinear exponential fits of SI to corresponding echo time were used to calculate T2*-metrics. All qualitative and quantitative evaluations were region specific (proximal, middle, distal). Linear mixed effects models assessed associations of side and region with T2*-metrics. Spearman correlations evaluated relationships between outcome measures. Within and between study visits, significant side-to-side differences in T2*-metrics were found and were significantly impacted by leg dominance (p<0.05). Pre-season T2*-metrics correlated with COT in T2*-metrics, COT in T2*-metrics correlated with COT in qualitative PT grades, and post-season T2*-metrics correlated with max changes in VISA-P scores (ρ≥0.64). Quantitative T2*-metrics can detect PT and may be capable of predicting the onset of pathology. T2*-metrics could benefit the clinical management of PT: it is sensitive to changes in pathologic severity over time, and therefore can serve as a quantitative metric to guide treatment and evaluate intervention efficacy.
The rotator cuff tendinopathy is one of the most common shoulder problems leading to full-thickness rotator cuff tendon tear and, eventually, to degenerative arthritis. Recent research on rotator cuff
Tendinopathy is a disease associated with pain and
Though retear rates following rotator cuff repair are well established, we set out to review current literature to determine when early retears occurred (defined as <12m following surgery), and examine which pre- and post-operative variables might affect outcome. Pubmed, Medline, and CINAHL were searched for literature published from 2011 to 2021 using specific search terms. The inclusion criteria were studies reporting retear rates within 12 months of initial surgical repair. Exclusionary criteria were studies that included partial thickness tears, and studies that did not use imaging modalities within 12 months to assess for retears. PRISMA guidelines were followed, identifying a total of 10 papers. A combined total of 3372 shoulders included (Mean age 56 −67 years). The most common modality used to identify early retears were ultrasound scan and MRI. 6 of the 10 studies completed imaging at 0-3 months, 6 studies imaged at 3-6 months and 6 studies imaged at 6-12 months. Across all studies, there was a 17% early retear rate (574 patients). Of these, 13% occurred by 3 months, whilst the peak for retears occurred at 3-6 months (82%) and 5% occurred at 6-12 months. The risk of retear was higher in larger tears and extensive
Tendons mainly consist of collagen in order to withstand high tensile forces. Compared to other, high turnover tissues, cellularity and vascularity in tendons are low. Thus, the natural healing process of tendons takes long and can be problematic. In case of injury to the enthesis, the special transition from tendon over cartilage to bone is replaced by a fibrous scar tissue, which remains an unsolved problem in rotator cuff repair. To improve tendon healing, many different approaches have been described using scaffolds, stem cells, cytokines, blood products, gene therapy and others. Despite promising in vitro and in vivo results, translation to patient care is challenging. In clinics however, tendon auto- or allografts remain still first choice to augment tendon healing if needed. Therefore, it is important to understand natural tendon properties and natural tendon healing first. Like in other tissues, senescence of tenocytes seems to play an important role for
Energy storing tendons such as the human Achilles and equine superficial digital flexor tendon (SDFT) are prone to age-related injury. Tendons have poor healing capacity and a lack of effective treatments can lead to ongoing pain, reduced function and re-injury. It is therefore important to identify the mechanisms underpinning age-related tendinous changes in order to develop more effective treatments. Our recent single cell sequencing data has shown that tendon cell populations have extensive heterogeneity and cells housed in the tendon interfascicular matrix (IFM) are preferentially affected by ageing. There is, however, a lack of established surface markers for cell populations in tendon, limiting the capacity to isolate distinct cell populations and study their contribution to age-related
Background. Weightbearing computed tomography scans allow for better understanding of foot alignment in patients with Progressive Collapsing Foot Deformity. However, soft tissue integrity cannot be assessed via WBCT. As performing both WBCT and magnetic resonance imaging is not cost effective, we aimed to assess whether there is an association between specific WBCT and MRI findings. Methods. A cohort of 24 patients of various stages of PCFD (mean age 51±18 years) underwent WBCT scans and MRI. In addition to signs of sinus tarsi impingement, four three-dimensional measurements (talo-calcaneal overlap, talo-navicular coverage, Meary's angle axial/lateral) were obtained using a post processing software (DISIOR 2.1, Finland) on the WBCT datasets. Sinus tarsi obliteration, spring ligament complex and tibiospring ligament integrity, as well as tibialis posterior
During aging, tendons demonstrate substantial disruptions in homeostasis, leading to impairments in structure-function. Impaired tendon function contributes to substantial declines quality of life during aging. Aged tendons are more likely to undergo spontaneous rupture, and the healing response following injury is impaired in aged tendons. Thus, there is a need to develop strategies to maintain tendon homeostasis and healing capacity through the lifespan. Tendon cell density sharply declines by ∼12 months of age in mice, and this low cell density is retained in geriatric tendons. Our data suggests that this decline in cellularity initiates a degenerative cascade due to insufficient production of the extracellular matrix (ECM) components needed to maintain tendon homeostasis. Thus, preventing this decline in tendon cellularity has great potential for maintaining tendon health. Single cell RNA sequencing analysis identifies two changes in the aged tendon cell environment. First, aged tendons primarily lose tenocytes that are associated with ECM biosynthesis functions. Second, the tenocytes that remain in aged tendons have disruptions in proteostasis and an increased pro-inflammatory phenotype, with these changes collectively termed ‘programmatic skewing'. To determine which of these changes drives homeostatic disruption, we developed a model of tenocyte depletion in young animals. This model decreases tendon cellularity to that of an aged tendon, including decreased biosynthetic tenocyte function, while age-related programmatic skewing is absent. Loss of biosynthetic tenocyte function in young tendons was sufficient to induce homeostatic disruption comparable to natural aging, including deficits in ECM organization, composition, and material quality, suggesting loss biosynthetic tenocytes as an initiator of
Re-rupture rates after rotator cuff repair remain high because of inadequate biological healing at the tendon-bone interface. Single-growth factor therapies to augment healing at the enthesis have so far yielded inconsistent results. An emerging approach is to combine multiple growth factors over a spatiotemporal distribution that mimics normal healing. We propose a novel combination treatment of insulin-like growth factor 1 (IGF-1), transforming growth factor β1 (TGF-β1) and parathyroid hormone (PTH) incorporated into a controlled-release tyraminated poly-vinyl-alcohol hydrogel to improve healing after rotator cuff repair. We aimed to evaluate this growth factor treatment in a rat chronic rotator cuff tear model. A total of 30 male Sprague-Dawley rats underwent unilateral supraspinatus tenotomy. Delayed rotator cuff repairs were then performed after 3 weeks, to allow
Introduction: Tendon injury is an important cause of injury in racehorses, with flexor tendon and suspensory ligament injuries accounting for 46% of all musculoskeletal injuries at British racecourses (. 1. ). In the galloping horse the superficial digital flexor tendon (SDFT) undergoes strains that are close to the functional limit of the tendon (. 2. ) and it is hypothesised that exercise induces cumulative microdamage in the SDFT of skeletally mature horses which may predispose to clinical disease. We hypothesised that matrix metalloproteinases (MMPs) play a role in the process of
Introduction. Differing levels of tendon retraction are found in full-thickness rotator cuff tears. The pathophysiology of
As we grow older, the risk of
A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient’s quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach. A group of eight patients revised due to a PJI with a previous lateral approach was compared with a group of 21 revised THAs without infection, performed using the same approach. The primary variables of the study were the fibril diameter, as seen in transmission electron microscopy (TEM), and the total degeneration score (TDS), as seen under the light microscope. An analysis of bacteriology, classification of infection, and antibiotic treatment was also performed.Aims
Methods
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
The exact pathways of collagen remodeling in tendon tissue are not well understood. Therefore, we have established an ex vivo 3D collagen gel-based system and we studied the remodeling capacity of two different TSPC lines from young, Y-TSPC and aged/degenerative, A-TSPC donors. Here, we specifically focused on investigating the involvement of integrin receptors in the remodeling process. Integrins are transmembrane receptors consisting of alpha (a) and beta (b) subunits, which form cell-to-matrix bonds, activate various pathways and thereby control cell proliferation, differentiation and survival. Y- and A-TSPC were derived from human Achilles tendons and are fully described in Kohler et al. 2013. RT-PCR was used to assess the expression of collagen-binding integrins in the TSPC cultivated in collagen gels. Next, a1 and a11 integrins were silenced by stable lentiviral delivery of target-specific shRNA in the Y-TSPC. Control (con-shRNA), integrin (a1-shRNA) and integrin a11 (a11-shRNA) virus-containing supernatant was given for 24h and then cells were selected with 50 microg./ml zeocin for 10 days. The integrin knockdown (KD) efficiency was assessed by quantitative PCR and western blotting. Last, functional tests were carried out by time-lapse recording gel contraction of four cell groups (Y-TSPC+con, Y-TSPC+a1KD, Y-TSPC+a11KD, and A-TSPC). Among the screened integrins we found that integrin a1 and a11 were significantly downregulated in A-TSPC with 3.8 and 5.6 folds, correspondingly. Therefore, to mimic the A-TSPC we carried out a gene KD of a1 and a11 in Y-TSPC. PCR and western blot clearly validated the efficient KD. Analyses of collagen contraction, revealed that Y-TSPC+a11KD significantly reduced collagen contractability comparable to A-TSPC. This indicated the indispensable role of this integrin in the signaling pathway of collagen matrix remodeling. In respect to integrin a1, we found that this receptor did not affect the contraction rate of Y-TSPC, which was similar to Y-TSPC+con. To our knowledge we have now identified for the first time the critical role of a11 integrin receptor in tendon collagen remodeling, and a follow up analysis of its exact downstream cascade is on the way. Future efforts in deciphering how tendon matrix makeover is regulated can lead to innovation in preventive strategies for
Metabolic disorders are frequently associated with
Objectives. To investigate the appropriate dose and interval for the administration
of triamcinolone acetonide (TA) in treating tendinopathy to avoid
adverse effects such as
Dislocation of the hip remains a major complication after periacetabular tumour resection and endoprosthetic reconstruction. The position of the acetabular component is an important modifiable factor for surgeons in determining the risk of postoperative dislocation. We investigated the significance of horizontal, vertical, and sagittal displacement of the hip centre of rotation (COR) on postoperative dislocation using a CT-based 3D model, as well as other potential risk factors for dislocation. A total of 122 patients who underwent reconstruction following resection of periacetabular tumour between January 2011 and January 2020 were studied. The risk factors for dislocation were investigated with univariate and multivariate logistic regression analysis on patient-specific, resection-specific, and reconstruction-specific variables.Aims
Methods
Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors. Cite this article:
Introduction. recent studies recognised metabolic abnormalities as additional factors in the development of rotator cuff (RC) tendinopathy. It has been hypothesised that the insertional area of this tendon is susceptible to degenerative changes due to intrinsic hypovascularization. The mechanisms underlying this process are not yet clear. In this study we attempted to confirm if larger lesions of the RC are related to impaired vasodilatatory response of the local circulation in conditions of “hemodynamic stress”. Patients & Methods. it was assumed that impaired vasal reaction to “hemodynamic stress” was a systemic condition. This phenomenon should therefore be not limited to the critical area of the tendon tear. Given this assumption post-ischemic vasodilation of brachial artery was studied through an echo-doppler (US) evaluation. 50 patients (mean 61 ± 4, range 50–65) all scheduled for surgical rotator cuff repair following a tendon tear, were enrolled. Three preoperative measurements of the brachial artery diameter before and after application of an ischemic band were collected. The size of the lesions was later assessed at the time of surgery. A statistical analysis was carried on to investigate the correlation between US assessment of brachial artery diameter and the corresponding size of the RC lesions. UCLA and ASES scores were also measured to assess clinical and functional outcomes. Results. Patients were classified into 4 groups according to Cofield's classification of tear size; respectively, 4 patients had massive lesions, 32 large, 10 medium and 4 had finally small lesions. The extent of the RC lesion showed an inverse correlation with the diameter of brachial artery after an ischemic stimulus: an increase in size of the lesion corresponded to lower mean post-ischemic diameter of the vessel (p <0.0001). UCLA and ASES data showed no statistically significant differences between the subgroups (p > 0.534). Discussion/Conclusion. It is not clear why the insertional area of tendons composing the RC is hypovascularised. We hypothesised there is an imbalance between local vasodilator and vasoconstrictor factors. The prevalence of vasoconstrictor substances determines a reduced post-ischemic vasodilation. The data presented provide the basis for the future identification of vascular impairment that could underlie the beginning of
Aims: 1 To assess the histological changes in patients with Achilles tendinopathy. 2 To map the distribution of nerves and nerve endings within the Achilles tendon. Methods: Tendon biopsy specimens were taken from patients with spontaneous (ie previously painless) Achilles rupture patients and chronic painful tendinopathy patients. ‘Normal’ cadaveric /lacerated tendon biopsies were used for comparison. Sections were stained with H&
E for basic histology. Immunolocalisation of nerve tissue was performed with 2 anti-neurofilament antibodies. Non-specific immunoglobulin was used as a negative control. Results: The number of nerves and nerve endings found within the normal tendons and both groups of degenerate tendons was very low. Only 30% of the normal tendon sections showed any positive staining at all. Compared to 36% of ruptured tendon and 43% of the painful tendinopathy sections. Conclusions: Tendon rupture and chronic painful tendinopathy biopsies ALL show widespread degenerative changes. There is a paucity of nerve tissue within these tendons, which may have implications for the neurogenic hypothesis of
Achilles tendinitis can result, through inflammatory procedures, to
Local dysregulation of the proteolytic matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) is a feature of
Aim: The purpose of this study was to evaluate the cytokine molecules present in a rat tendinopathy model and in the torn edge of human rotator cuff tendon in an attempt to understand their role in
1. The avascular zone in the tendon of the supraspinatus near its insertion was not seen in the other tendons comprising the rotator cuff, except for the superior portion of the insertion of the infraspinatus which, on occasions, showed a small avascular area. The biceps tendon, however, also showed an avascular zone as it coursed over the head of the humerus. It is suggested that the anatomical disposition of these tendons makes them subject to constant pressure from the head of the humerus, which tends to wring out the blood supply to these tendons when the arm is held in the resting position of adduction and neutral rotation. 2. Although this study did not produce any evidence that the relative avascularity of the tendons over a prolonged period could be indicted as the sole cause of the degenerative changes that so commonly occur, it was noted that the degenerative changes occurred first and that they were always most extensive in the areas of avascularity. It was also observed that the zones of relative avascularity preceded, and were not the result of, the degenerative changes. 3. With the onset of
The overall incidence of cuff tears increases with age, individuals over 80years having a 51% incidence of a tear. Currently, the aetiology of rotator cuff tears remains unclear and successful repair is achieved in only 30% patients. Matrix metalloproteinases (MMPs) have roles in a wide range of physiological processes including placentation and embryogenesis, tissue remodelling and wound healing. However, the ability of MMPs to dissolve extracellular matrix has been linked to a variety of pathological processes including rheumatoid arthritis, osteoarthritis, periodontitis and multiple sclerosis, which involve excessive matrix destruction. Production of gelatinase MMPs by torn rotator cuff has been demonstrated. The objectives of this study were to examine the expression of MMPs and their association with histological changes in full thickness tears of the rotator cuff. Rotator cuff tissue was obtained from ten patients (age 40–80years) undergoing surgical repair. The size of tear was 1–4.5cm; time from presentation to surgery was 1 month (acute) to between 0.5–4years (chronic). Immunohistochemical staining with commercial monoclonal antibodies to a range of MMPs, endothelial, macrophage and fibroblast markers was performed. Production of gelatinase MMPs was measured by gelatin zymography on tissue culture supernatant. Visualisation used a standard DAB chromagen technique. In the acute specimens there was an infiltrate of macrophages with little collagen degeneration; the fibro-blasts were MMP1 positive and endothelial cells MMP2 positive. At 12 months post-tear mature collagen, plump fibroblasts and proliferating endothelial cells were identified adjacent to the resection edge. Towards the torn edge areas of lower cellularity, sparse vascularity and collagen degeneration were observed. Vimentin positive, CD68 negative cells within this matrix were rounded with foamy cytoplasm, and intensely positive for MMP1 and MMP2, and positive for MMP-3, -10, -11, -13 and -14. Tissue culture supernatant demonstrated active and latent MMP2 production in all cases. The prolonged interval between trauma and surgical repair, with potential pharmacological intervention, remedial physiotherapy and disuse immobility, make assessment of the factors contributing to
Introduction. The exact mechanisms leading to tendinopathies and tendon ruptures remain poorly understood while their occurrence is clearly associated with exercise. Overloading is thought to be a major factor contributing to the development of tendon pathologies. However, as animal studies have shown, heavy loading alone won't cause tendinopathies. It has been speculated, that malfunctioning adaptation or healing processes might be involved, triggering
Failure of healing is a well-known problem after repair of the rotator cuff. This study aimed to investigate if early repair of trauma-related full-thickness rotator cuff tears (FTRCTs) could prevent this failure. In this prospective trial, 62 consecutive patients (14 women (23%), 48 men (77%); median age 61 years (interquartile range (IQR) 54 to 65)) with trauma-related FTRCT underwent arthroscopic single-row repair within six weeks of trauma. Tendon integrity was assessed one year after surgery using the Sugaya score on MR images. Patients were followed up with Western Ontario Rotator Cuff (WORC) index, EuroQol visual analogue scale (EQ VAS), and the Constant–Murley score (CS) two years after repair.Aims
Patients and Methods
The supraspinatus tendon (SP) often ruptures. Gray established that the tendinous insertion always attaches to the highest facet of the greater tubercle of the humerus. Our osteological study of 124 shoulders in men and women between the ages of 35 and 94 years refocuses on the humeral insertion of the SP in relation to infraspinatus (IS) and teres minor (TM). We found type-I SFs (cubic) in 53 shoulders (43%) and type-II SFs (rectangular or oblong) in 21 (17%). Type-III (ellipsoid) SFs were present in 20 shoulders (16%) and type-IV (angulated or sloping) in 11 (9%). SFs were type V (with tuberosity) in 12 shoulders (10%) and type VI (pitted) in three (2%). The facet area of the SP, IP and TM varied from 49 mm, 225 mm and 36mm2. Of the three muscles, the IS facet was consistently the largest (p <
0.05) and shaped rectangularly. The SP inserted in a cubic or rectangular facet format in 75% of people. SP facet-size may relate to
The rotator cuff is sited on the anatomical neck of the humerus and is formed by the insertion of the supraspinatus (SP), infraspinatus (IS), teres minor (TM) and subscapularis. All play a vital role in the movement of the glenohumeral joint, and the anatomy is of critical importance in arthroscopic rotator cuff repair. We undertook an osteological and gross anatomical dissection study of the insertion mechanism of these tendons, in particular the SP . The SP inserts by a triple or quadruple mechanism. The ‘heel’ (medial) and capsule fuse, inserting into the anatomical neck proximal to the anterior facet of the greater humeral tubercle. The ‘foot arch’ inserts as a strong, flat, fibrous tendon into the facet. This area is cuboidal, rectangular, or ellipsoid, and measures 36 mm. 2. to 64 mm. 2. In about 5%, the insertion is fleshy (pitted), rendering it weaker than a tendinous attachment. The ‘toe’ lips over the edge of the facet laterally and fuses with the periosteum, fibres of the inter-transverse ligament and the IS. A proximal ‘hood’ of about 4 mm stretches down inferiorly and fuses with the periosteum of the humeral shaft. The subacromial or subdeltoid synovial bursa are sited laterally. The IS and TM insert into the middle and posterior facets (225 mm and 36 mm. 2. ) at respective angles of 80° and 115°. The inferior portion of the TM facet is not fused with the shoulder capsule. The subscapularis inserts broadly into the lesser tubercle, and the superior fibres fuse with the shoulder capsule and intertransverse ligament. The insertion of the subscapularis does not contribute directly to the formation of the ‘hood’, which belongs exclusively to the SP, IP and TM. This study confirms the complexity of the SP insertion and suggests that an unfavourable attachment or biomechanical anatomical malalignment may lead to eventual
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. 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 Objectives
Methods
If a modular convertible total shoulder system
is used as a primary implant for an anatomical total shoulder arthroplasty,
failure of the prosthesis or the rotator cuff can be addressed by
converting it to a reverse shoulder arthroplasty (RSA), with retention
of the humeral stem and glenoid baseplate. This has the potential
to reduce morbidity and improve the results. In a retrospective study of 14 patients (15 shoulders) with a
mean age of 70 years (47 to 83) we reviewed the clinical and radiological
outcome of converting an anatomical shoulder arthroplasty (ASA)
to a RSA using a convertible prosthetic system (SMR system, Lima,
San Daniele, Italy). The mean operating time was 64 minutes (45 to 75). All humeral
stems and glenoid baseplates were found to be well-fixed and could
be retained. There were no intra-operative or early post-operative
complications and no post-operative infection. The mean follow-up was 43 months (21 to 83), by which time the
mean visual analogue scale for pain had decreased from 8 pre-operatively
to 1, the mean American Shoulder and Elbow Surgeons Score from 12
to 76, the mean Oxford shoulder score from 3 to 39, the mean Western
Ontario Osteoarthritis of the Shoulder Score from 1618 to 418 and
the mean Subjective shoulder value from 15 to 61. On radiological review, one patient had a lucency around the
humeral stem, two had stress shielding. There were no fatigue fractures
of the acromion but four cases of grade 1 scapular notching. The use of a convertible prosthetic system to revise a failed
ASA reduces morbidity and minimises the rate of complications. The
mid-term clinical and radiological results of this technique are
promising. Cite this article:
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. We conducted a systematic review of the scientific literature
with specific inclusion and exclusion criteria.Introduction
Methods
The role of inflammatory cells and their products in tendinopathy is not completely understood. Pro-inflammatory cytokines are upregulated after oxidative and other forms of stress. Based on observations that increased cytokine expression has been demonstrated in cyclically-loaded tendon cells we hypothesised that because of their role in oxidative stress and apoptosis, pro-inflammatory cytokines may be present in rodent and human models of tendinopathy. A rat supraspinatus tendinopathy model produced by running overuse was investigated at the genetic level by custom micro-arrays. Additionally, samples of torn supraspinatus tendon and matched intact subscapularis tendon were collected from patients undergoing arthroscopic shoulder surgery for rotator-cuff tears and control samples of subscapularis tendon from ten patients with normal rotator cuffs undergoing arthroscopic stabilisation of the shoulder were also obtained. These were all evaluated using semiquantitative reverse transcription polymerase chain-reaction and immunohistochemistry. We identified significant upregulation of pro-inflammatory cytokines and apoptotic genes in the rodent model (p = 0.005). We further confirmed significantly increased levels of cytokine and apoptotic genes in human supraspinatus and subscapularis tendon harvested from patients with rotator cuff tears (p = 0.0008). These findings suggest that pro-inflammatory cytokines may play a role in tendinopathy and may provide a target for preventing tendinopathies.
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. 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 Aims
Methods
This study reports the clinical and sonographic
outcome of arthroscopic rotator cuff repair in patients aged ≥ 70 years
and aimed to determine factors associated with re-tear. A total
of 69 consecutive repairs were performed in 68 patients with a mean
age of 77 years (70 to 86). Constant-Murley scores were collected
pre-operatively and at one year post-operatively. The integrity
of the repair was assessed using ultrasound. Re-tear was detected
in 20 of 62 patients (32%) assessed with ultrasound. Age at operation We conclude that arthroscopic rotator cuff repair in patients
aged ≥ 70 years is a successful procedure. The gender and age of
the patient are important factors to consider when planning management. Cite this article:
We have studied cellular and vascular changes in different stages of full thickness tears of the rotator cuff. We examined biopsies from the supraspinatus tendon in 40 patients with chronic rotator cuff tears who were undergoing surgery and compared them with biopsies from four uninjured subscapularis tendons. Morphological and immunocytochemical methods using monoclonal antibodies directed against leucocytes, macrophages, mast cells, proliferative and vascular markers were used. Histological changes indicative of repair and inflammation were most evident in small sized rotator cuff tears with increased fibroblast cellularity and intimal hyperplasia, together with increased expression of leucocyte and vascular markers. These reparative and inflammatory changes diminished as the size of the rotator cuff tear increased. Marked oedema and degeneration was seen in large and massive tears, which more often showed chondroid metaplasia and amyloid deposition. There was no association between the age of the patient and the duration of symptoms. In contrast, large and massive tears showed no increase in the number of inflammatory cells and blood vessels. Small sized rotator cuff tears retained the greatest potential to heal, showing increased fibroblast cellularity, blood vessel proliferation and the presence of a significant inflammatory component. Tissue from large and massive tears is of such a degenerative nature that it may be a significant cause of re-rupture after surgical repair and could make healing improbable in this group.
The effect of timing of a manipulation under
anaesthetic (MUA) and injection of corticosteroid and local anaesthetic for
the treatment of frozen shoulder has attracted little attention
to date. All studies describe a period of conservative treatment
before proceeding to an MUA. Delay has been associated with a poorer
outcome. We present a retrospective review of a prospectively collected,
single-surgeon, consecutive series of 246 patients with a primary
frozen shoulder treated by MUA within four weeks of presentation.
The mean duration of presenting symptoms was 28 weeks (6 to 156),
and time to initial post-operative assessment was 26 days (5 to
126). The Oxford shoulder score (OSS) improved by a mean of 16 points
(Wilcoxon signed-ranks test,
p <
0.001) with a mean OSS at this time of 43 (7 to 48). Linear
regression analysis showed no correlation between the duration of
presenting symptoms and OSS at initial follow-up
(R2 <
0.001) or peri-operative change in OSS (R2 <
0.001)
or OSS at long-term follow-up
(R2 <
0.03). Further analysis at a mean of 42 months (8 to 127)
revealed a sustained improvement with a mean OSS of 44 (16 to 48). A good outcome follows an MUA and injection of corticosteroid
and local anaesthetic in patients with primary frozen shoulder,
independent of the duration of the presenting symptoms, and this
improvement is maintained in the long term.
The aim of this study was to investigate the occurrence of tissue hypoxia and apoptosis at different stages of tendinopathy and tears of the rotator cuff. We studied tissue from 24 patients with eight graded stages of either impingement (mild, moderate and severe) or tears of the rotator cuff (partial, small, medium, large and massive) and three controls. Biopsies were analysed using three immunohistochemical techniques, namely antibodies against HIF-1α (a transcription factor produced in a hypoxic environment), BNip3 (a HIF-1α regulated pro-apoptotic protein) and TUNEL (detecting DNA fragmentation in apoptosis). The HIF-1α expression was greatest in mild impingement and in partial, small, medium and large tears. BNip3 expression increased significantly in partial, small, medium and large tears but was reduced in massive tears. Apoptosis was increased in small, medium, large and massive tears but not in partial tears. These findings reveal evidence of hypoxic damage throughout the spectrum of pathology of the rotator cuff which may contribute to loss of cells by apoptosis. This provides a novel insight into the causes of degeneration of the rotator cuff and highlights possible options for treatment.