Long non-coding RNA MFAT1 promotes skeletal muscle fibrosis by modulating the miR-135a-5p-Tgfbr2/Smad4 axis as a ceRNA.

Fibrosis after skeletal muscle injury is common in sports and can cause irreversible damage to the biomechanical properties of skeletal muscle. Long non-coding RNAs (lncRNAs) have been validated to act as important modulators in the fibrosis of various organs. Here, we reported a novel lncRNA (the skeletal muscle fibrosis-associated transcript 1, lnc-MFAT1), which was highly expressed in skeletal muscle fibrosis. We demonstrate that lnc-MFAT1 knockdown can reduce TGFß-induced fibrosis in vitro and attenuate skeletal muscle fibrosis after acute contusion in mice. Further study showed that lnc-MFAT1 acted as a competitive endogenous RNA of miR-135a-5p. Besides, the miR-135a-5p inhibition obviously promoted TGFß-induced fibrosis in vitro via enhancing its target genes Tgfbr2/Smad4. Moreover, we discovered that lnc-MFAT1 regulates Tgfbr2/Smad4 expression by sponging miR-135a-5p to exert competing endogenous RNA function, resulting in TGFß pathway activation. In conclusion, our study identified a crucial role of lnc-MFAT1-miR-135a-Tgfbr2/Smad4 axis in skeletal muscle fibrosis, providing a promising treatment option against skeletal muscle fibrosis.

miR-122-5p negatively regulates the transforming growth factor-ß/Smad signaling pathway in skeletal muscle myogenesis.

Regeneration remains a major challenge in skeletal muscle repair after injury. Recently, transforming growth factor-ß (TGF-ß)/Smad pathway was found to play an important role in inhibiting myogenesis, a crucial stage in skeletal muscle regeneration. In our previous study, microRNA-122-5p (miR-122) was proved to have the function of downregulating TGF-ß/Smad pathway. Theoretically, miR-122 might also be involved in the process of skeletal muscle myogenesis through the regulation of TGF-ß/Smad pathway. In this study, we aimed to investigate the impact of miR-122 on skeletal muscle myogenesis and explore its underlying mechanism. Results showed that miR-122 and myogenic markers were downregulated in C2C12 cells after TGF-ß stimulation, and miR-122 overexpression could restore the myogenesis inhibited by TGF-ß. We then located TGFBR2 as the direct target of miR-122 and discovered the effect of miR-122 overexpression could be rescued by TGFBR2 overexpression. Further, the downstream molecules of TGFBR2 in the TGF-ß/Smad pathway were found to be suppressed by miR-122. In conclusion, miR-122 could suppress the TGF-ß/Smad signalling pathway by directly targeting TGFBR2 and, consequently, restore myogenesis. SIGNIFICANCE OF THE STUDY: Regeneration remains a major challenge in skeletal muscle repair after injury. In this study, it was found that miR-122 could suppress the TGF-ß/Smad signalling pathway by directly targeting TGFBR2 and, consequently, restore myogenesis. Our findings could inspire future experiments on the role of miRs in skeletal muscle diseases and future translational studies on potential novel gene therapy for skeletal muscle injury.

Editorial Commentary: Arthroscopy for Borderline Developmental Dysplasia of the Hip: Selection Determines the Outcomes.

Although the literature has presented results that favored arthroscopic procedures in treating borderline developmental dysplasia of the hip (BDDH), it remains controversial whether arthroscopic surgery would be better than periacetabular osteotomy for BDDH. Instead of a debate on the application of arthroscopy, the issue worthy of discussion should be distinguishing suitable BDDH candidates for hip arthroscopy. First, identification of patients with real BDDH is critical for making management choices. Second, it should be distinguished whether the major symptoms result from mechanical lesions or functional hip instability. Third, once hip arthroscopy is suggested for BDDH patients, relative contraindications such as advanced age and osteoarthritis should be taken into consideration, in addition to labral repair and capsular closure or plication intraoperatively. In conclusion, more long-term and high-grade evidence is still demanded to end the debate, but we believe that an individualized management strategy based on an accurate diagnosis and comprehensive assessment will bring optimal outcomes for BDDH patients.

Influence of Femoral Version on the Outcomes of Hip Arthroscopic Surgery for Femoroacetabular Impingement or Labral Tears: A Systematic Review and Meta-analysis.

BACKGROUND: It remains controversial whether abnormal femoral version (FV) affects the outcomes of hip arthroscopic surgery for femoroacetabular impingement (FAI) or labral tears. PURPOSE: To review the outcomes of hip arthroscopic surgery for FAI or labral tears in patients with normal versus abnormal FV. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: Embase, PubMed, and the Cochrane Library were searched in July 2020 for studies reporting the outcomes after primary hip arthroscopic surgery for FAI or labral tears in patients with femoral retroversion (<5°), femoral anteversion (>20°), or normal FV (5°-20°). The primary outcome was the modified Harris Hip Score (mHHS), and secondary outcomes were the visual analog scale (VAS) for pain, Hip Outcome Score-Sport-Specific Subscale (HOS-SSS), Non-Arthritic Hip Score (NAHS), failure rate, and patient satisfaction. The difference in preoperative and postoperative scores (Δ) was also calculated when applicable. RESULTS: Included in this review were 5 studies with 822 patients who underwent hip arthroscopic surgery for FAI or labral tears; there were 166 patients with retroversion, 512 patients with normal version, and 144 patients with anteversion. Patients with retroversion and normal version had similar postoperative mHHS scores (mean difference [MD], 2.42 [95% confidence interval (CI), -3.42 to 8.26]; P = .42) and ΔmHHS scores (MD, -0.70 [96% CI, -8.56 to 7.15]; P = .86). Likewise, the patients with anteversion and normal version had similar postoperative mHHS scores (MD, -3.09 [95% CI, -7.66 to 1.48]; P = .18) and ΔmHHS scores (MD, -1.92 [95% CI, -6.18 to 2.34]; P = .38). Regarding secondary outcomes, patients with retroversion and anteversion had similar ΔNAHS scores, ΔHOS-SSS scores, ΔVAS scores, patient satisfaction, and failure rates to those with normal version, although a significant difference was found between the patients with retroversion and normal version regarding postoperative NAHS scores (MD, 5.96 [95% CI, 1.66-10.26]; P = .007) and postoperative HOS-SSS scores (MD, 7.32 [95% CI, 0.19-14.44]; P = .04). CONCLUSION: The results of this review indicated that abnormal FV did not significantly influence outcomes after hip arthroscopic surgery for FAI or labral tears.

Sex-Based Differences in Clinical Outcomes After Arthroscopic Anterior Shoulder Stabilization: Results at 5-Year Follow-up.

BACKGROUND: The influence of patient sex on clinical outcomes after arthroscopic anterior shoulder stabilization is unclear. PURPOSE: To investigate sex-based differences in clinical outcomes after arthroscopic anterior shoulder stabilization. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective study was conducted among 76 patients who underwent arthroscopic anterior shoulder stabilization from February 2010 to December 2017. The patients were grouped by sex. The recurrence rate of instability was compared, as were pre- and postoperative pain scores, functional outcome scores, and active range of motion (ROM). Postoperative magnetic resonance imaging (MRI) was also performed for structural assessment of the glenohumeral joint. RESULTS: No significant difference was found in the recurrence rate between female and male patients (13.3% vs 14.8%; P ≥ .999; risk ratio, 1.107 [95% CI, 0.266-4.597]). Compared with male patients, female patients had a significantly lower preoperative Constant score (94.4 ± 6.4 vs 85.4 ± 11.1; P = .002), forward flexion (173.8° ± 10.7° vs 154.0° ± 33.8°; P = .011), abduction (171.0° ± 18.4° vs 142.7° ± 39.9°; P = .001), and external rotation (76.6° ± 21.6° vs 67.7° ± 20.4°; P = .037). Postoperatively, female patients had a significantly lower Simple Shoulder Test score compared with men (8.8 ± 1.9 vs 10.3 ± 1.6; P = .005). The mean changes from pre- to postoperative Rowe score (43.6 ± 21.4 vs 31.5 ± 19.8; P = .044), Constant score (9.9 ± 8.9 vs 0.8 ± 8.1; P = .002), forward flexion (24.0 ± 36.2 vs 4.2 ± 10.9; P = .013), abduction (36.0 ± 38.3 vs 7.6 ± 18.4; P < .001), and external rotation (19.7 ± 21.3 vs 6.7 ± 26.2; P = .023) in female patients were significantly higher than those in the men. There were no sex-based differences on any MRI parameter measured. CONCLUSION: Female patients had a similar recurrence rate as that of male patients after arthroscopic anterior shoulder stabilization. Most postoperative clinical outcome measures showed no significant difference between the sexes. Despite worse preoperative values, more significant improvements in postoperative shoulder function and active ROM were seen in women.

Outcome Comparison of Graft Bridging and Superior Capsule Reconstruction for Large to Massive Rotator Cuff Tears: A Systematic Review.

BACKGROUND: Graft bridging (GB) and superior capsule reconstruction (SCR) were developed to treat large to massive rotator cuff tears (RCTs); however, the outcome differences between GB and SCR remain unclear. PURPOSE: To systematically review and compare the outcomes of GB and SCR for large to massive RCT. STUDY DESIGN: Systematic review. METHODS: A systematic review was performed via a comprehensive search of PubMed, Embase, and the Cochrane Library. Studies of GB or SCR were included according to the inclusion and exclusion criteria. The primary outcome was Constant-Murley score at the final follow-up. Secondary outcomes included the American Shoulder and Elbow Surgeons score, visual analog scale score for pain, active shoulder range of motion, and graft healing rate. Complication rate was the safety outcome measure. Outcomes were summarized into group SCR and group GB, and the results were compared statistically (P < .05). RESULTS: A total of 23 studies were included in this review: 238 repairs from the 5 studies in group SCR and 593 repairs from the 18 studies in group GB. For group SCR and group GB, the mean age was 61.6 and 63.3 years, and the mean follow-up was 18.0 and 40.1 months, respectively. Overall, both procedures demonstrated improvement of clinical outcomes. When compared with group SCR, group GB had significantly higher mean differences of the Constant-Murley score (41.9 vs 19.8), American Shoulder and Elbow Surgeons score (39.3 vs 33.8), visual analog scale score for pain (4.4 vs 3.4), and active external rotation at side (15.3 vs 9.3). No statistically significant difference was detected in the mean difference of active forward flexion, internal rotation, abduction, and graft healing rate between the groups. The complication rates were 0.84% (2 of 238) in group SCR and 0.67% (4 of 593) in group GB. CONCLUSION: In general, GB showed significantly better clinical and functional outcomes postoperatively than SCR, with a similar complication rate. The available fair-quality evidence suggested that GB might be a better choice for large to massive RCT. More high-quality randomized controlled studies are required to further evaluate the relative benefits of the 2 procedures.

Relationship Between Age at Initial Shoulder Instability and Overall Outcomes After Arthroscopic Bankart Repair: Mean 6-Year Follow-up.

BACKGROUND: Age at surgery plays a crucial role in the frequency of recurrent shoulder instability. However, there are few studies that evaluate the relationship between age at initial shoulder instability and overall outcomes after stabilization surgery. PURPOSE: To compare clinical outcomes and structural changes after arthroscopic Bankart repair in patients who experienced initial shoulder instability during adolescence versus those with later onset instability. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study included patients who underwent arthroscopic Bankart repair at a single institution between 2007 and 2017. Comparisons were made between patients who experienced initial shoulder instability during adolescence (age 13-19 years; group A) and those with later onset instability (age 20-35 years; group B). Clinical outcomes (recurrence rate, postoperative pain, functional scores, active range of motion, and return to sports) and structural changes demonstrated by magnetic resonance imaging (MRI) were evaluated at minimum 2-year follow-up. In addition, functional outcomes within each group were compared between the patients with and without postoperative recurrence. RESULTS: A total of 58 patients were included (24 patients in group A and 34 patients in group B). The mean follow-up was 72.1 months. Group A demonstrated a significantly higher recurrence rate than group B (41.7% vs 11.8%, respectively; P = .009; risk ratio, 5.36 [95% CI, 1.43-20.09]) as well as significantly lower Rowe (76.9 ± 20.1 vs 88.7 ± 13.2, respectively; P = .01) and Constant-Murley scores (92.2 ± 7.6 vs 96.3 ± 4.2, respectively; P = .01). Postoperative MRI revealed no significant structural differences between the groups regarding the glenoid labrum, glenohumeral cartilage, or osseous reaction around the implanted anchors. In group A, patients with recurrence had less satisfaction regarding postoperative sports level than those without recurrence, whereas in group B, patients with recurrence had more postoperative pain and functional impairment compared with those without recurrence. CONCLUSION: Initial shoulder instability during adolescence was associated with a higher recurrence rate and lower functional scores after arthroscopic Bankart repair compared with later onset instability, although no significant structural differences were found between the groups on MRI at a mean 6-year follow-up.

Location of the Suture Anchor in Hill-Sachs Lesion Could Influence Glenohumeral Cartilage Quality and Limit Range of Motion After Arthroscopic Bankart Repair and Remplissage.

BACKGROUND: No study has reported clinical evidence for cartilage change in the glenohumeral joint or the cause of loss in range of motion (ROM) after arthroscopic Bankart repair with remplissage technique (BR). PURPOSE: To investigate the postoperative features of glenohumeral joint cartilage, ROM, and anchor placement for remplissage at a minimum of 2 years of follow-up after BR and to analyze the correlations. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 21 patients who underwent BR received follow-up for a minimum of 2 years. At both preoperative assessment and final follow-up, passive shoulder ROM, Oxford Shoulder Instability Score, Simple Shoulder Test score, and Single Assessment Numerical Evaluation score were assessed. All patients underwent 3.0-T magnetic resonance imaging (MRI) examination at final follow-up. The clinical outcomes, glenohumeral cartilage or Hill-Sachs lesion-related MRI parameters, and their potential correlations were analyzed. RESULTS: The mean follow-up was 55.0 months (range, 24-119 months). Compared with preoperative assessment, all functional scores significantly improved (P < .001). At the final follow-up, a significant ROM loss (>15°) of external rotation (ER) at the side (ER0) was found in 12 patients, among whom 8 patients had significant ROM loss of ER at 90° of abduction as well. Further, 12 patients with decreased ER had significantly higher signal intensity of cartilage on the anterior, middle, and posterior humeral head (anterior, P = .002; middle, P < .001; posterior, P < .001) than 9 patients with normal ER. The ratio of the width of the remplissage anchor to the diameter of the humeral head (w:d ratio) was significantly greater (P = .031) in the decreased ER group than in the normal ER group. Correlation analysis showed that signal intensity on the posterior humeral head and ER0 loss (ΔER0) had a significantly positive correlation (r = 0.516; P = .034), while the w:d ratio and ΔER0 had a significantly positive correlation (r = 0.519; P = .039). CONCLUSION: At a minimum of 2 years of follow-up, patients who underwent BR showed significant clinical improvement compared with preoperative assessment, except for limitations in ER. The glenohumeral cartilage degeneration (higher signal intensity) after BR had a significantly positive correlation with the postoperative ER loss, which was found to be associated with a relatively medial placement of the remplissage anchor.

Tendon Healing Progression Evaluated With Magnetic Resonance Imaging Signal Intensity and Its Correlation With Clinical Outcomes Within 1 Year After Rotator Cuff Repair With the Suture-Bridge Technique.

BACKGROUND: After a rotator cuff (RC) is repaired, its signal intensity (SI) on magnetic resonance imaging (MRI) gradually changes to normal and could reflect the degree of RC healing. Nevertheless, it remains unclear how long it takes for SI to recover to normal and whether the SI progression correlates with clinical outcomes after RC repair (RCR). PURPOSE: To serially evaluate the SIs of the repaired RC tendon on MRI and the postoperative clinical outcomes and then analyze the correlation between them. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This study prospectively included 25 patients who underwent arthroscopic RCR with the suture-bridge technique between June 2016 and July 2017. Twenty-three patients accepted full follow-ups at 1, 3, 6, 9, and 12 months. Before surgery and at each follow-up, visual analog scale (VAS) for pain and 4 functional scores were evaluated: Constant-Murley score, American Shoulder and Elbow Surgeons shoulder evaluation form, modified University of California at Los Angeles score, and Fudan University shoulder score. The patients underwent MRI examinations at every follow-up. The values of the signal/noise quotient at the distal (SNQd) and proximal (SNQp) areas were calculated to evaluate the SI of the repaired tendon. The correlations of clinical outcomes with SNQd and SNQp values were analyzed, and subgroup analyses were performed. RESULTS: Overall, the mean postoperative VAS score significantly decreased at postoperative 1 month (P < .001), and the functional scores were all significantly higher than the preoperative values at 6 months (all P < .001). SNQd and SNQp values were both significantly higher than normal at 1 and 3 months (all P < .001) and reduced to normal after 9 and 6 months, respectively. Correlation analyses showed that the SNQp value significantly correlated with VAS score (positive) and all functional scores (negative) at 1 and 3 months postoperatively. Further comparison indicated that the patients with VAS score >3 had higher SNQp values than patients with VAS score ≤3 at 1 and 3 months postoperatively (both P = .01). CONCLUSION: After RCR with the suture-bridge technique, it took longer for SI to become relatively normal than it did to have a significant clinical improvement. Early after surgery (1-3 months), worse clinical outcome correlated with higher SI on proximal cuff tendon.

Hip Arthroscopic Surgery in Borderline Developmental Dysplastic Hips: A Systematic Review.

BACKGROUND: It remains controversial whether hip arthroscopic surgery should be applied to patients with a borderline developmental dysplastic hip (BDDH). PURPOSE: To review the outcomes of hip arthroscopic surgery for a BDDH and which factors influence these outcomes. STUDY DESIGN: Systematic review. METHODS: PubMed, Embase, and the Cochrane Library were searched through March 2018 for studies reporting the outcomes of primary hip arthroscopic surgery in patients with a BDDH. Inclusion in the review was based on the definition of a BDDH, patient-reported outcomes, and duration of follow-up. The primary outcome was the modified Harris Hip Score (mHHS). The failure rate, visual analog scale, satisfaction score, and patient-reported outcomes such as the Hip disability and Osteoarthritis Outcome Score were defined as secondary outcomes. RESULTS: Nine studies with 425 patients who underwent hip arthroscopic surgery were included in this review. The mean follow-up times ranged from 25.4 to 28.8 months across the studies. A significant improvement was obtained in the mHHS, with a mean score of 61.8 preoperatively to 82.8 postoperatively; all other patient-reported outcomes also improved significantly, except the 12-Item Short Form Health Survey mental component summary. The overall failure rate was 14.1%, and the mean reoperation rate was 8.5%. The rate of conversion to total hip arthroplasty ranged from 4.4% to 26.0%, and the rate of conversion to periacetabular osteotomy was 4.0%. Combined defects such as cartilage damage, hip osteoarthritis, ligamentum teres tears, and femoroacetabular impingement could influence the outcomes after arthroscopic surgery in BDDHs. CONCLUSION: Hip arthroscopic surgery was demonstrated to be a promising approach for BDDHs, but the outcomes could be influenced by multiple risk factors. A higher level of evidence is still needed to support current findings.

Advantages of an Attached Semitendinosus Tendon Graft in Anterior Cruciate Ligament Reconstruction in a Rabbit Model.

BACKGROUND: The semitendinosus tendon graft with an intact tibial insertion has a sustainable blood supply and might be beneficial for graft maturation after anterior cruciate ligament reconstruction (ACLR); however, its potential advantages for graft tendon-bone healing is still unclear. HYPOTHESIS: Intact tibial insertion of the hamstring tendon can preserve enough blood supply to keep the harvested tendon alive, which can improve tendon-bone healing and the biomechanical strength of the graft. STUDY DESIGN: Controlled laboratory study. METHODS: Sixty-four healthy New Zealand White rabbits underwent unilateral ACLR with a semitendinosus tendon autograft after random enrollment into 2 groups (study group, n = 32 rabbits with semitendinosus tendon-preserved tibial insertions; control group, n = 32 rabbits with free semitendinosus tendons). At weeks 3, 6, 12, and 24, 8 rabbits in each group were sacrificed to evaluate tendon-bone healing by histologic staining, micro-computed tomography (micro-CT) examination, and biomechanical test. RESULTS: The grafts in the study group maintained a similar cell count with no signs of necrosis or hypocellularity across all time points, but the grafts in the control group underwent a characteristic stage of necrosis at weeks 3 and 6. Sharpey-like fibers were observed from postoperative 3 weeks at the tendon-bone interface in the study group, and a normal insertion-like structure was formed at week 12, which became more mature at week 24. In the control group, however, Sharpey-like fibers could not be observed until week 12, and a normal transition through cartilage from bone to tendon was not observed at any time point. Histologic scores of the tendon-bone interface in the study group were significantly higher than those in the control group at week 6 ( P = .04), week 12 ( P < .001), and week 24 ( P = .04). As compared with the control group via micro-CT, the study group had a significantly smaller bone tunnel area at week 6 ( P = .01) and larger bone volume/total volume at week 3 ( P = .0026) and week 6 ( P = .01). Also, the study group had a significantly higher failure load at weeks 12 and 24 (both P = .03) and a significantly higher stiffness at week 24 ( P < .001) versus the control group. CONCLUSION: The semitendinosus tendon graft with an intact tibial insertion in ACLR would bypass the graft avascular necrosis stage, which improves tendon-bone healing and biomechanical strength. CLINICAL RELEVANCE: An alive graft in ACLR could improve tendon-bone healing and the biomechanical strength of the graft, which might be beneficial to early and intensive rehabilitation after ACLR.