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

Critical shoulder angle (CSA), lateral acromial angle (LAA), and acromion index (AI) are common radiologic parameters used to distinguish between patients with rotator cuff tears (RCT) and those with an intact rotator cuff. This study aims to assess the predictive power of these parameters in degenerative RCT. This retrospective study included data from 92 patients who were divided into two groups: the RCT group, which included 47 patients with degenerative full-thickness supraspinatus tendon tears, and a control group of 45 subjects without tears. CSA, AI, and LAA measurements from standardized true anteroposterior radiographs were independently derived and analyzed by two orthopedic surgeons. Receiver operating characteristic (ROC) analyses were performed to determine the cutoff values. No significant differences were found between patients in the RCT and control groups in age (p = 0.079), gender (p = 0.804), or injury side (p = 0.552). Excellent inter-observer reliability was seen for CSA, LAA, and AI values. Mean CSA (38.1°) and AI (0.72) values were significantly larger in the RCT group than in the control group (34.56° and 0.67°, respectively, p < 0.001) with no significant difference between groups for LAA (RCT, 77.99° vs. control, 79.82°; p = 0.056). ROC analysis yielded an area under the curve (AUC) of 0.815 for CSA with a cutoff value of 37.95°, and CSA was found to be the strongest predictor of the presence of a RCT, followed by AI with an AUC of 0.783 and a cutoff value of 0.705. We conclude that CSA and AI may be useful predictive factors for degenerative RCT in the Turkish population

Introduction. Platelet Rich Plasma (PRP) is widely used in clinical praxis. Especially the effects in musculoskeletal repair studies are diverse and an augmentation of healing processes stays questionable. However, diverse cell culture studies reported promising results, which seem not be transferable into the clinical situation. We therefore performed a cell culture study which better reflects the clinical situation: the autologous stimulation of human tendon cells with PRP. Materials and Methods. Human tenocyte-like cells (hTLCs) from 24 donors (12 male/female) with supraspinatus tendon tears were isolated and characterized. The donors were grouped into 4 groups according to their age (</> 65 years) and sex. During follow up, approximately 2.5 years after initial surgery, the patients donated blood for PRP preparation (Ethic vote and written informed consent). Growth factors and platelets were quantified and the effect of autologous stimulation of the hTLCs was measured by analysis of cell proliferation, Collagen I synthesis and expression of Collagen I, III and Osteocalcin. Results. The platelet concentration for the 4 groups was between 3.6–4.5 × 10. 5. platelets/µl (reference level: 1.5–3×10. 5. platelets/µl blood). PRP contained high amounts of IGF-1, lower amounts of TGF-β1 and PDGF-AB. PDGF-AB concentration significantly correlated with platelet concentration and the TGF-β1 concentration. The amounts of BMP-7 and −12 were underneath the detection limits of the assays. Cell proliferation was positively affected by PRP exposure when compared to controls (2% FCS and 10% FCS) (p<0.05). However, the expression and synthesis of Collagen I was significantly reduced compared to controls. Collagen III expression was partly increased, while Osteocalcin expression was not affected. Discussion. PRP is a source of growth factors such as IGF-1, TGF-β and PDGF-AB. It has a high potential to stimulate cell proliferation, which might have a positive effect in clinical applications. However, the decreased expression and synthesis of Collagen I, the most important Collagen in the tendon, might explain the, to date, less satisfactory clinical results. PRPs might have their potential in chronic situation with pain reducing function rather than in acute healing situations. Further studies are necessary to better understand these mechanisms