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Improvement of clinical outcomes of rotator cuff pathology requires in-depth understanding of the underlying cellular and molecular mechanisms of healing. This study presents a robust murine model of supraspinatus repair to serve as a standard research tool for basic and translational investigations into signaling pathways, gene expression, and the effect of biologic augmentation approaches.

Object Extreme lateral interbody fusion (ELIF) is a popular technique for anterior fixation of the thoracolumbar spine. Clinical and radiological outcome studies are required to assess safety and efficacy. The aim of this study was to describe the functional and radiological impact of ELIF in a degenerative disc disease population with a longer follow-up and to assess the durability of this procedure. Methods Demographic and perioperative data for all patients who had undergone ELIF for degenerative lumbar disorders between 2007 and 2011 were collected. Trauma and tumor cases were excluded. For radiological outcome, the preoperative, immediate postoperative, and latest follow-up coronal Cobb angle, lumbar sagittal lordosis, bilateral foraminal heights, and disc heights were measured. Pelvic incidence (PI) and PI–lumbar lordosis (PI-LL) mismatch were assessed in scoliotic patients. Clinical outcome was evaluated using the Oswestry Disability Index (ODI) and visual analog scale (VAS), as well as the Macnab criteria. Results One hundred forty-five vertebral levels were surgically treated in 90 patients. Pedicle screw and rod constructs and lateral plates were used to stabilize fixation in 77% and 13% of cases, respectively. Ten percent of cases involved stand-alone cages. At an average radiological follow-up of 12.6 months, the coronal Cobb angle was 10.6° compared with 23.8° preoperatively (p < 0.0001). Lumbar sagittal lordosis increased by 5.3° postoperatively (p < 0.0001) and by 2.9° at the latest follow-up (p = 0.014). Foraminal height and disc height increased by 4 mm (p < 0.0001) and 3.3 mm (p < 0.0001), respectively, immediately after surgery and remained significantly improved at the last follow-up. Separate evaluation of scoliotic patients showed no statistically significant improvement in PI and PI-LL mismatch either immediately postoperatively or at the latest follow-up. Clinical evaluation at an average follow-up of 17.6 months revealed an improvement in the ODI and the VAS scores for back, buttock, and leg pain by 21.1% and 3.7, 3.6, and 3.7 points, respectively (p < 0.0001). According to the Macnab criteria, 84.8% of patients had an excellent, good, or fair functional outcome. New postoperative thigh numbness and weakness was detected in 4.4% and 2.2% of the patients, respectively, which resolved within the first 3 months after surgery in all but 1 case. Conclusions This study provides what is to the authors' knowledge the most comprehensive set of radiological and clinical outcomes of ELIF in a fairly large population at a midterm follow-up. Extreme lateral interbody fusion showed good clinical outcomes with a low complication rate. The procedure allows for at least midterm clinically effective restoration of disc and foraminal heights. Improvement in coronal deformity and a small but significant increase in sagittal lordosis were observed. Nonetheless, no significant improvement in the PI-LL mismatch was achieved in scoliotic patients.

The ideal period of restricted weight-bearing and motion following ACL reconstruction remains undefined. In a murine model, improved healing was noted for animals immobilized for a brief period of 5 days. This work may serve as an initial step in determining the ideal time period in a clinical population.

In patients with LSS and DS, minimally invasive decompression is associated with lower reoperation and fusion rates, less slip progression, and greater patient satisfaction than open surgery.

Increasing evidence shows that aldosterone and specific microRNAs (miRs) contribute to vascular smooth muscle cell (VSMC) calcification. In this study, we aim to explore the mechanistic links between miR-34b/c and aldosterone in VSMC calcification. VSMC calcification models were established both in vitro and in vivo. First, the levels of aldosterone, miR-34b/c and special AT-rich sequence-binding protein 2 (SATB2) were measured. Then, miR-34b/c mimics or inhibitors were transfected into VSMCs to evaluate the function of miR-34b/c. Luciferase reporter assays were used to demonstrate whether SATB2 was a direct target of miR-34b/c. Aldosterone and SATB2 were found to be markedly upregulated during VSMC calcification, whereas miR-34b/c expression was downregulated. Treatment with the mineralocorticoid receptor (MR) antagonist eplerenone inhibited VSMC calcification. In aldosterone-induced VSMC calcification, miR-34b/c levels were downregulated and SATB2 protein was upregulated. Furthermore, miR-34b/c overexpression alleviated aldosterone-induced VSMC calcification as well as inhibited the expression of SATB2 protein, whereas miR-34b/c inhibition markedly enhanced VSMC calcification and upregulated SATB2 protein. In addition, luciferase reporter assays showed that SATB2 is a direct target of miR-34b/c in VSMCs. Overexpression of SATB2 induced Runx2 overproduction and VSMC calcification. Therefore, miR-34b/c participates in aldosterone-induced VSMC calcification via a SATB2/Runx2 pathway. As miR-34b/c appears to be a negative regulator, it has potential as a therapeutic target of VSMC calcification.

Mechanical stress has an important effect on tendon-to-bone healing. The purpose of the present study was to compare tendon-to-bone healing in animals exposed to either tendon unloading (botulinum toxin injection) or excessive loading (treadmill running) in a murine rotator cuff repair model. Forty-eight C57BL/6 mice underwent unilateral supraspinatus tendon detachment and repair. Mice in the unloaded group were injected with botulinum toxin to the supraspinatus muscle. The contralateral shoulder of the unloaded group was used as a control. Mice were euthanized at 1, 2, and 4 weeks after surgery and evaluated with hematoxylin-eosin and immunohistochemical (IHC) staining for Ihh, Gli1, Wnt3a, and β-catenin. The positive staining area on IHC and the Modified Tendon Maturing Score were measured. The score of the unloaded group was significantly higher (better healing) than that of the treadmill group at 4 weeks. Ihh and the glioma-associated oncogene homolog 1 (Gli1) positive area in the unloaded group were significantly higher than those of the control group at 1 week. The peak time-points of the Ihh and Gli1 positive area was 1 week for the unloaded group and 2 weeks for the treadmill group. The Wnt3a positive area in the unloaded group was significantly higher than that of the control group at 2 weeks. The β-catenin positive area in the unloaded group was significantly higher than that of the treadmill group and the control group at 1 week. Our data indicated that the unloaded group has superior tendon maturation compared to the treadmill running group. Excessive tendon loading may delay the tendon healing process by affecting the activity of Ihh and Wnt/β-Catenin pathways.

Subacromial impingement of the rotator cuff is understood as a contributing factor in the development of rotator cuff tendinopathy. However, changes that occur in the impinged tendon are poorly understood and warrant further study. To enable further study of rotator cuff tendinopathy, we performed a controlled laboratory study to determine feasibility and baseline characteristics of a new murine model for subacromial impingement. This model involves surgically inserting a microvascular clip into the subacromial space in adult C57Bl/6 mice. Along with a sham surgery arm, 90 study animals were distributed among time point groups for sacrifice up to 6 weeks. All animals underwent bilateral surgery (total N = 180). Biomechanical, histologic, and molecular analyses were performed to identify and quantify the progression of changes in the supraspinatus tendon. Decreases in failure force and stiffness were found in impinged tendon specimens compared to sham and no-surgery controls at all study time points. Semi-quantitative scoring of histologic specimens demonstrated significant, persistent tendinopathic changes over 6 weeks. Quantitative real-time polymerase chain reaction analysis of impinged tendon specimens demonstrated persistently increased expression of genes related to matrix remodeling, inflammation, and tendon development. Overall, this novel murine subacromial impingement model creates changes consistent with acute tendonitis, which may mimic the early stages of rotator cuff tendinopathy. A robust, simple, and reproducible animal model of rotator cuff tendinopathy is a valuable research tool to allow further studies of cellular and molecular mechanisms and evaluation of therapeutic interventions in rotator cuff tendinopathy. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2780-2788, 2018.