Effects of corticosteroids and platelet-rich plasma on synoviocytes in IL-1ß-induced inflammatory condition.

AIMS: Corticosteroid injections are used to treat shoulder pain. Platelet-rich plasma (PRP) is known to have anti-inflammatory and anabolic effects, as well as cytoprotective effects against corticosteroids. Thus, this study was to investigate the effects of co-treatment of corticosteroid and PRP on anti-inflammatory and matrix homeostasis of synoviocytes in IL-1ß-induced inflammatory conditions. MATERIALS AND METHODS: Synoviocytes were cultured with 1 ng/mL IL-1ß, 1 µM dexamethasone, and 10% (vol/vol) Platelet-poor plasma (PPP), PRP200, PRP1000, and PRP4000 X 103/µL. Gene expressions of pro-inflammatory and anti-inflammatory cytokines, degradative enzymes, and their inhibitors were evaluated and protein synthesis of degradative enzymes and their inhibitors were also examined. RESULTS: Corticosteroid modulated anti-inflammatory and pro-inflammatory cytokines, and subsequent PRP treatment did not interfere with the effect of a corticosteroid and modulated the gene expressions of cytokines such as TNF-α and IL-4, which were not regulated by the corticosteroid alone. Gene expressions and protein expressions of degradative enzymes and their inhibitors were suppressed by corticosteroid. Additional PRPs did not alter the gene expression and protein regulated by the corticosteroid and inhibited the gene expression of ADAMTS-5 and protein synthesis of MMP-9 and ADAMTS-5, which were not modulated by the corticosteroid alone. CONCLUSION: Corticosteroid regulated the inflammation and synovial homeostasis. When PRP and the corticosteroid were used together, it exhibited synergistic effects on synoviocytes by regulating the parts that were not controlled by corticosteroid alone while not interfering with the effects of the corticosteroid in an inflammatory condition.

Intratendinous Injection of Mesenchymal Stem Cells for the Treatment of Rotator Cuff Disease: A 2-Year Follow-Up Study.

PURPOSE: To assess the mid-term safety and efficacy of an intratendinous injection of autologous adipose tissue-derived mesenchymal stem cells (AD MSCs) for rotator cuff disease at 2-year follow-up. METHODS: The first part of the study consisted of 3 dose-escalation groups, with 3 patients each, for the evaluation of safety: low-dose (1.0 × 107 cells), mid-dose (5.0 × 107), and high-dose (1.0 × 108) groups. For the second part, we planned to include 9 patients receiving the high dose for the evaluation of exploratory efficacy. Clinical outcomes were assessed according to pain, range of motion, muscle strength, functional scores, overall satisfaction and function, and presence of failure. Structural outcomes included changes in volume of tendon defects measured using magnetic resonance imaging. RESULTS: This study enrolled 19 patients (9 for the first part and 10 for the second part) with partial-thickness rotator cuff tears. There were no treatment-related adverse events at minimum 2-year follow-up. Intratendinous injection of AD MSCs reduced shoulder pain by approximately 90% at 1 and 2 years in the mid- and high-dose groups. The strength of the supraspinatus, infraspinatus, and teres minor significantly increased by greater than 50% at 2 years in the high-dose group. Shoulder function measured with 6 commonly used scores improved for up to 2 years in all dose groups. Structural outcomes evaluated with magnetic resonance imaging showed that the volume of bursal-sided defects in the high-dose group nearly disappeared at 1 year and did not recur at up to 2 years. No failures-defined as the performance of any kind of shoulder surgery or return of the Shoulder Pain and Disability Index score to the preinjection level-occurred during follow-up. CONCLUSIONS: This study showed continued safety and efficacy of an intratendinous injection of AD MSCs for the treatment of partial-thickness rotator cuff tears over a 2-year period through regeneration of tendon defects. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Anterior capsular abnormality: another important MRI finding for the diagnosis of adhesive capsulitis of the shoulder.

OBJECTIVE: To evaluate the usefulness of anterior capsular abnormality, thickening, and abnormal signal intensity on MRI for the diagnosis of adhesive capsulitis of the shoulder. MATERIALS AND METHODS: This retrospective study included 29 patients with adhesive capsulitis and 20 controls. Clinical criteria with significant restricted passive motion was used for the diagnosis of adhesive capsulitis. The anterior capsular thickness and signal intensity were evaluated on the thickest portion of anterior glenohumeral joint capsule, located deep to the subscapularis muscle. In addition, the previously known MR findings of adhesive capsulitis, such as humeral and glenoid capsular thickness in axillary recess, maximal axillary capsular thickness, and coracohumeral ligament thickness, were measured. The presence of humeral and glenoid capsular abnormal hyperintensity in axillary recess, abnormal hyperintensity, and obliteration of the subcoracoid fat triangle were also evaluated. RESULTS: All MRI findings significantly differed between adhesive capsulitis and controls. Among MR findings, multivariable analysis showed that anterior capsular thickness, maximal axillary capsular thickness, and anterior capsular abnormal hyperintensity were variables that could differentiate adhesive capsulitis from the control group, with odds ratios of 7.97, 17.75, and 12.41, respectively (p < 0.05). In ROC analysis, the anterior capsular thickness showed high diagnostic performances with an AUC of 0.897. The cut-off value of anterior capsular thickness at 3.5 mm showed excellent diagnostic accuracy, with sensitivity of 68.97% and specificity of 100%. CONCLUSIONS: Anterior capsular abnormality, thickening, and abnormal hyperintensity can be used for the diagnosis of adhesive capsulitis of shoulder, in addition to previously known abnormal MRI findings.

Changes of fatty infiltration according to the immediate postoperative time point in magnetic resonance imaging after arthroscopic rotator cuff repair.

PURPOSE: Fatty infiltration (FI) is known to be an irreversible change which continues degeneration after rotator cuff repair. Previous studies evaluated postoperative changes in FI using a preoperative baseline. This study aimed to investigate the changes in FI using an immediate postoperative baseline. We hypothesized that FI was progressed more when measured relative to an immediate postoperative baseline than to a preoperative baseline. METHODS: From 2008 to 2010, 77 patients who met the following criteria were included in this study: arthroscopic rotator cuff repair of a full-thickness rotator cuff tear and presence of preoperative (approximately 1 month before surgery), immediate postoperative (approximately 3 days after surgery), and 1-year postoperative (at least 9 months to 1 year after surgery) magnetic resonance imaging (MRI) undertaken. The exclusion criteria were: absence of any of the three MRIs, isolated subscapularis repair, and rotator cuff repair with margin convergence only. The MRIs were examined to assess the Goutallier grade of the rotator cuff muscles for the assessment of FI. Structural integrity was evaluated using the Sugaya classification. Measurements 1 year after surgery were compared with those at the preoperative and immediate postoperative time points according to the integrity. RESULTS: In the total and retear group, FI in the supraspinatus and infraspinatus 1 year after surgery did not change significantly relative to the preoperative baseline (all n.s.), but progressed compared to the immediate postoperative baseline (all p < 0.001). In the retear group, FI in the supraspinatus and infraspinatus reduced for seven and two of 20 patients, respectively, compared with the preoperative baseline; however, no patients showed a reduced FI compared with the immediate postoperative baseline. CONCLUSIONS: The results of the study showed that the changes in FI reduced, remained or progressed in accordance with the baseline and structural integrity. FI progressed when compared with the immediate postoperative baseline than with the preoperative baseline. The immediate postoperative time point would be considered as the baseline to monitor the true changes of FI after repair. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Degree of tendon degeneration and stage of rotator cuff disease.

PURPOSE: While tendon degeneration has been known to be an important cause of rotator cuff disease, few studies have objectively proven the association of tendon degeneration and rotator cuff disease. The purpose of this study was to investigate changes of tendon degeneration with respect to the stage of rotator cuff disease. METHODS: A total of 48 patients were included in the study: 12 with tendinopathy, 12 with a partial-thickness tear (pRCT), 12 with a full-thickness tear (fRCT), and 12 as the control. A full-thickness supraspinatus tendon sample was harvested en bloc from the middle portion between the lateral edge and the musculotendinous junction of the tendon using a biopsy punch with a diameter of 3 mm. Harvested samples were evaluated using a semi-quantitative grading scale with 7 parameters after haematoxylin and eosin staining. RESULTS: There was no significant difference in age, gender, symptom duration, and Kellgren-Lawrence grade between the groups except for the global fatty degeneration index. All of the seven parameters were significantly different between the groups and could be categorized as follows: early responders (fibre structure and arrangement), gradual responder (rounding of the nuclei), after-tear responders (cellularity, vascularity, and stainability), and late responder (hyalinization). The total degeneration scores were not significantly different between the control (6.08 ± 1.16) and tendinopathy (6.67 ± 1.83) (n.s.). However, the score of pRCT group (10.42 ± 1.31) was greater than that of tendinopathy (P < 0.001), and so was the score of fRCT (12.33 ± 1.15) than that of pRCT (p = 0.009). CONCLUSION: This study showed that the degeneration of supraspinatus tendon increases as the stage of rotator cuff disease progresses from tendinopathy to pRCT, and then to fRCT. The degree of degeneration of tendinopathy was not different from that of normal but aged tendons, and significant tendon degeneration began from the stage of pRCT. The clinical relevance of the study is that strategies and goals of the treatment for rotator cuff disease should be specific to its stage, in order to prevent disease progression for tendinopathy and pRCT, as well to restore the structural integrity for fRCT. LEVEL OF EVIDENCE: Diagnostic, Level I.

Changes of Muscle Atrophy According to the Immediate Postoperative Time Point in Magnetic Resonance Imaging After Arthroscopic Rotator Cuff Repair.

PURPOSE: The purpose of this study was to investigate changes of rotator cuff muscles after arthroscopic rotator cuff repair by measuring the muscle atrophy (MA) of rotator cuff muscles at the preoperative, immediate postoperative, and 1-year postoperative time points. METHODS: Inclusion criteria were (1) arthroscopic rotator cuff repair of a full-thickness rotator cuff tear and (2) the presence of the preoperative (approximately 1 month before surgery), immediate postoperative (approximately 3 days after surgery), and 1-year postoperative magnetic resonance imaging (MRI) undertaken at our institution. Exclusion criteria were (1) the absence of any of the 3 MRIs, (2) isolated subscapularis repair, and (3) rotator cuff repair with margin convergence only. The MA was assessed with the modified tangent sign (TS), the occupation ratio (OR), and the cross-sectional areas (CSAs) of the supraspinatus and infraspinatus. Structural integrity was evaluated using Sugaya's classification. Measurements 1 year after surgery were compared with those of the preoperative and the immediate postoperative time points according to the integrity. RESULTS: Seventy-seven patients were included in the study. The TS improved in 23.4% of patients and worsened in 6.5% with the preoperative baseline, while it improved in 5.2% of patients and worsened in 23.4% (P < .001). The OR improved in 24.5% of patients but worsened in 3.9% with the preoperative baseline, while it improved in 13.0% and worsened in 11.7% patients (P < .001). The CSAs of the supraspinatus and infraspinatus changed by 8.7% ± 24.5% and -0.3% ± 16.1% with the preoperative baseline and by -12.8% ± 20.3% and -10.5% ± 14.9% with the immediate postoperative baseline (all P < .001). CONCLUSIONS: The results of the study showed that changes of the MA after arthroscopic rotator cuff repair were different with respect to the baselines and the integrity. Generally, the MA measured with the immediate postoperative baseline worsened, whereas that measured with the preoperative baseline improved. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial.

Mesenchymal stem cells (MSCs) are known to have a potential for articular cartilage regeneration. However, most studies focused on focal cartilage defect through surgical implantation. For the treatment of generalized cartilage loss in osteoarthritis, an alternative delivery strategy would be more appropriate. The purpose of this study was to assess the safety and efficacy of intra-articular injection of autologous adipose tissue derived MSCs (AD-MSCs) for knee osteoarthritis. We enrolled 18 patients with osteoarthritis of the knee and injected AD MSCs into the knee. The phase I study consists of three dose-escalation cohorts; the low-dose (1.0 × 10(7) cells), mid-dose (5.0 × 10(7)), and high-dose (1.0 × 10(8)) group with three patients each. The phase II included nine patients receiving the high-dose. The primary outcomes were the safety and the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) at 6 months. Secondary outcomes included clinical, radiological, arthroscopic, and histological evaluations. There was no treatment-related adverse event. The WOMAC score improved at 6 months after injection in the high-dose group. The size of cartilage defect decreased while the volume of cartilage increased in the medial femoral and tibial condyles of the high-dose group. Arthroscopy showed that the size of cartilage defect decreased in the medial femoral and medial tibial condyles of the high-dose group. Histology demonstrated thick, hyaline-like cartilage regeneration. These results showed that intra-articular injection of 1.0 × 10(8) AD MSCs into the osteoarthritic knee improved function and pain of the knee joint without causing adverse events, and reduced cartilage defects by regeneration of hyaline-like articular cartilage.

Multimodal analgesia for arthroscopic rotator cuff repair: a randomized, placebo-controlled, double-blind trial.

BACKGROUND: The aim of the study was to investigate whether a multimodal analgesia (MMA) protocol reduces postoperative pain and opioids consumption in patients undergoing arthroscopic rotator cuff repair. METHODS: Fifty-four patients scheduled for arthroscopic rotator cuff repair were randomly assigned to either the MMA group or the control group. The primary outcome was visual analog scale (VAS) for pain. Secondary outcome measures included the time required for the VAS pain to reduce to that of a blood draw, (PCA) consumption, rescue morphine consumption, night awakening, and opioid-related side effects. RESULTS: The MMA group showed significantly less postoperative pain at postoperative 5 h, and 9 a.m. and 5 p.m. at 4th postoperative day (P < 0.001, = 0.040, and 0.013, respectively). MMA also shortened the time for postoperative pain to reduce down to the blood draw pain level from 5 days in the control group to 2 days in the MMA group. MMA also significantly reduced PCA consumption for up to 24 h postoperatively (P = 0.038) and rescue morphine consumption during the first 6 h and between 48 and 60 h postoperatively (P = 0.036 and 0.044, respectively). No significant differences were observed between the MMA and control groups with respect to side effects. CONCLUSION: The MMA protocol used in this study was found to reduce postoperative pain and opioid consumption during the acute postoperative period after arthroscopic rotator cuff repair without increasing side effects after arthroscopic rotator cuff repair.

Effects of Quality of Integrity on Clinical and Structural Outcomes of Rotator Cuff Repair: A Retrospective Cohort Study of 504 Cases.

BACKGROUND: The clinical implications of structural integrity have been a subject of long debate. The oversimplified binary categorization of structural integrity into either healing or retear, along with faulty preoperative baselines for comparison, may contribute to the controversy. PURPOSE: To determine how the quality of structural integrity in a repaired cuff tendon affects both clinical and structural outcomes by dividing the patients into groups based on integrity and using the immediate postoperative baseline (time zero). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 504 patients with a full-thickness rotator cuff tear who underwent arthroscopic rotator cuff repair and were followed up for at least a year with magnetic resonance imaging (MRI) were included. The quality of structural integrity was graded using the Sugaya classification. To evaluate clinical outcomes, pain, range of motion, strength, functional scores, and overall satisfaction and function were used for within- and between-group analyses at the last follow-up. For the assessment of structural outcomes, the Goutallier classification for fatty infiltration (FI) and the tangent sign, occupation ratio, and normalized cross-sectional area for muscle atrophy (MA) were used. The baselines for these structural measurements were both the preoperative and the time-zero MRI scans. RESULTS: The mean clinical follow-up period was 31.8 ± 27.5 months, and the MRI follow-up period was 10.9 ± 5.3 months. There were 178 (35.3%), 228 (45.2%), 58 (11.5%), 14 (2.8%), and 26 (5.2%) shoulders with Sugaya grades 1, 2, 3, 4, and 5, respectively. Regardless of structural integrity, all clinical outcomes at a mean follow-up of 31.8 months after repair significantly improved compared with those before repair. Only in shoulders with Sugaya grade 1 did the FI of the supraspinatus muscle improve significantly from baseline. FI of the infraspinatus muscle did not change significantly in those with grades 1 and 2 but worsened in those with grades 3 and 5. MA measured using the occupation ratio improved significantly in shoulders with Sugaya grades 1 and 2 but declined in those with grade 5. CONCLUSION: This study established a correlation between improved structural integrity of the repaired cuff tendon and enhanced structural outcomes in rotator cuff muscles. Furthermore, the findings revealed that both FI and MA could be reversed in patients exhibiting high-quality structural integrity. However, these structural improvements were not mirrored in the clinical outcomes.

Comparative evaluation of in vivo osteogenic differentiation of fetal and adult mesenchymal stem cell in rat critical-sized femoral defect model.

Mesenchymal stem cells (MSCs) can be obtained from various sources. MSCs from different origins appear to have different preferences for differentiation. In this study, we have compared the in vivo osteogenic potential of adult MSCs from adipose tissue (AT) and bone marrow (BM) with fetal MSCs from umbilical cord (UC) and umbilical cord blood (UCB) by using a rat critical-sized femoral defect model. We have also sought to determine whether pretreatment with an osteogenic medium promotes osteogenesis in MSCs. Study groups were divided as follows: (1) defect only, (2) scaffold only, (3) AT MSCs in scaffolds, (4) BM MSCs in scaffolds, (5) UC MSCs in scaffolds and (6) UCB MSCs in scaffolds. Groups with MSCs were further divided with respect to their pretreatment. At 12 weeks after surgery, in vivo osteogenesis was measured radiographically and by micro-computed tomography (CT). Based on quantitative assessment by micro-CT, no significant difference of the mean bone volume fraction value (BV/TV) was seen between adult MSCs (AT and BM MSCs) and fetal MSCs (UC and UCB MSCs). The mean BV/TVs were significantly higher in non-pretreated BM MSC (14.2±1.4%) and UCB MSC (14.0±1.2%) and pretreated UC MSC (14.8±2.0%) than in those with the scaffold only (11.3±1.3%; P<0.05). In addition, AT (from 10.4±1.2% to 13.1±2.2%) and UC (from 10.3±0.7% to 14.8±2.0%) MSCs from solid tissues showed a significant increase in the mean BV/TV with pretreatment (P<0.05). In contrast, BM MSC (from 14.2±1.4% to 10.9±1.2%) and UCB MSC (from 14.0±1.2% to 11.6±1.0%) from non-solid tissues showed a significant decrease with pretreatment (P<0.05).

Changes in appearance of fatty infiltration and muscle atrophy of rotator cuff muscles on magnetic resonance imaging after rotator cuff repair: establishing new time-zero traits.

PURPOSE: To investigate whether and how arthroscopic rotator cuff repair changes the appearance of fatty infiltration and muscle atrophy as shown on magnetic resonance imaging (MRI) by comparing measurements taken before and immediately after surgery. METHODS: The first study determined appropriate measurements of fatty infiltration and muscle atrophy, and the second study assessed immediate postoperative changes caused by surgery per se. Forty-two patients who underwent arthroscopic shoulder surgery for reasons other than rotator cuff repair were included in the first study, and 101 patients who underwent arthroscopic rotator cuff repair were included in the second study. MRI was undertaken preoperatively and 3 days after surgery. Fatty infiltration was evaluated with the Goutallier grade and by measuring signal intensities of rotator cuff muscles, and muscle atrophy was assessed with the tangent sign, occupation ratio, and cross-sectional areas of muscles. RESULTS: In the first study, only the cross-sectional area of the subscapularis significantly changed after surgery and was excluded in the second study. In the second study, fatty infiltration seemingly improved by at least 1 grade in 50.0%, 75.0%, and 95.8% of patients with Goutallier grade 2, 3, and 4, respectively, in the supraspinatus (P < .001) and in 28.6%, 57.1%, and 66.7%, respectively, in the infraspinatus (P < .001). Muscle atrophy of the supraspinatus changed by at least 1 grade in 93.6% of patients with a grade 2 tangent sign and 100.0% with a grade 3 tangent sign, as well as 84.0% of patients with a grade 3 occupation ratio; cross-sectional areas of the supraspinatus and infraspinatus significantly increased by 21.6% and 7.0%, respectively (all P < .001). CONCLUSIONS: This study showed that arthroscopic rotator cuff repair changed the appearance of both fatty infiltration and muscle atrophy of the supraspinatus and infraspinatus on MRI. We suggest that these changes be considered when one is assessing rotator cuff muscle changes by comparing the appearance on MRI before surgery with that at a certain time after surgery. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Implications of Axis Inhibition Protein 2 in Breast Cancer Progression.

BACKGROUND/AIM: Although axis inhibition protein 2 (Axin2) has been reported to act as a tumour suppressor, recent findings suggest that it exhibits oncogenic effects by mediating Snail1-induced epithelial-mesenchymal transition (EMT) in breast cancer cells. EMT is a crucial biological process involved in the initiation of metastasis in cancer progression. This study elucidated the biological significance and mechanism of Axin2 in breast cancer using transcriptomic and molecular techniques. MATERIALS AND METHODS: The expression of Axin2 and Snail1 in MDA-MB-231 breast cancer cells was determined by western blotting analysis, and the role of Axin2 in breast cancer tumorigenesis was investigated in xenograft mouse models constructed using pLKO-Tet-shAxin2-transfected triple negative (TN) breast cancer cells. Additionally, the expression levels of EMT markers were determined using qRT-PCR, and clinical data were analysed using Kaplan-Meier (KM) plotter and The Cancer Genome Atlas (TCGA). RESULTS: Axin2 knockdown significantly decreased (p<0.001) the proliferation of MDA-MB-231 cells in vitro and attenuated (p<0.05) the tumorigenic potential of the cells in vivo. Moreover, Axin2 knockdown significantly increased the relative mRNA levels of epithelial markers but decreased the expression of mesenchymal markers in MDA-MB-231 cells. CONCLUSION: Axin2 may be involved in the progression of breast cancer, particularly triple-negative breast cancer, through the regulation of Snail1-induced EMT, making it a potential therapeutic target.

Prognostic factors affecting structural integrity after arthroscopic rotator cuff repair: a clinical and histological study.

BACKGROUND: Tendon degeneration contributes to rotator cuff tears; however, its role in postoperative structural integrity is poorly understood. The purpose of this study was to investigate the factors associated with postoperative structural integrity after rotator cuff repair, particularly focusing on the histology of tendons harvested intraoperatively. METHODS: A total of 56 patients who underwent primary arthroscopic rotator cuff repair between 2009 and 2011 were analyzed. A 3-mm-diameter sample of supraspinatus tendons was harvested en bloc from each patient after minimal debridement of the torn ends. Tendon degeneration was assessed using seven histological parameters on a semi-quantitative grading scale, and the total degeneration score was calculated. One-year postoperative magnetic resonance imaging was used to classify the patients based on retear. RESULTS: The total degeneration scores in the healed and retear groups were 13.93±2.03 and 14.08±2.23 (P=0.960), respectively. Arthroscopically measured anteroposterior (AP) tear sizes in the healed and retear groups were 24.30±12.35 mm and 36.42±25.23 mm (P=0.026), respectively. Preoperative visual analog scale pain scores at rest in the healed and retear groups were 3.54±2.37 and 5.16±2.16 (P=0.046), respectively. Retraction sizes in the healed and retear groups were 16.02±7.587 mm and 22.33±13.364 mm (P=0.037), respectively. The odds of retear rose by 4.2% for every 1-mm increase in AP tear size (P=0.032). CONCLUSIONS: The postoperative structural integrity of the rotator cuff tendon was not affected by tendon degeneration, whereas the arthroscopically measured AP tear size of the rotator cuff tendon was an independent predictor of retear.

Degenerative tendon matrix induces tenogenic differentiation of mesenchymal stem cells.

PURPOSE: Mesenchymal stem cells (MSCs) react dynamically with the surrounding microenvironment to promote tissue-specific differentiation and hence increase targeted regenerative capacity. Extracellular matrix (ECM) would be the first microenvironment to interact with MSCs injected into the tissue lesion. However, degenerative tissues would have different characteristics of ECM in comparison with healthy tissues. Therefore, the influence of degenerative ECM on tissue-specific differentiation of MSCs and the formation of matrix composition need to be considered for the sophisticated therapeutic application of stem cells for tissue regeneration. METHODS: Human degenerative tendon tissues were obtained from patients undergoing rotator cuff repair and finely minced into 2 ~ 3 mm fragments. Different amounts of tendon matrix (0.005 g, 0.01 g, 0.025 g, 0.05 g, 0.1 g, 0.25 g, 0.5 g, 1 g, and 2 g) were co-cultured with bone marrow MSCs (BM MSCs) for 7 days. Six tendon-related markers, scleraxis, tenomodulin, collagen type I and III, decorin, and tenascin-C, osteogenic marker, alkaline phosphatase (ALP), and chondrogenic marker, aggrecan (ACAN), were analyzed by qRT-PCR. Cell viability and senescence-associated beta-galactosidase assays were performed. The connective tissue growth factor was used as a positive control. RESULTS: The expressions of six tendon-related markers were significantly upregulated until the amount of tendon matrix exceeded 0.5 g, the point where the mRNA expressions of all six genes analyzed started to decrease. The tendon matrix exerted an inhibitory effect on ACAN expression but had a negligible effect on ALP expression. Cell viability did not change significantly over the culture period. The amount of tendon matrix exceeding 0.01 g significantly increased the SA-ßgal activity of BM MSCs. CONCLUSION: This study successfully demonstrated tendon ECM-stimulated tenogenesis of BM MSCs through an indirect co-culture system without the use of exogenous growth factors and the alteration of cellular viability. In contrast to the initial hypothesis, the tenogenesis of BM MSCs induced with the degenerative tendon matrix accompanied cellular senescence.

Clinical Implication of Glenohumeral and Subacromial Synovitis in Rotator Cuff Tears.

Background: Synovitis of the glenohumeral (GH) joint and the subacromial (SA) space is commonly observed during arthroscopic rotator cuff surgery. Purpose: To investigate the distribution, severity, and clinical implications of synovitis in the GH joint and SA space in patients with a full-thickness rotator cuff tear (RCT). Study Design: Case series; Level of evidence, 4. Methods: Data were retrospectively collected from 207 patients with a full-thickness RCT who underwent arthroscopic repair. Preoperative parameters used in the clinical assessment included pain, range of motion (ROM), muscle strength, and functional scores. Macroscopic assessment of synovitis was performed intraoperatively in the 3 regions of interest (ROIs) of the GH joint and 4 ROIS of the SA space using an evaluation system. The distribution and severity of synovitis and the association between synovitis and clinical assessment were evaluated. Results: Synovitis was more severe in the GH joint than in the SA space (P < .001). Synovitis in the posterior GH joint and the lateral SA space, where most of the rotator cuff was located, was the most severe area among the ROIs of the GH joint and the SA space, respectively (P < .05). All types of pain, except for pain at rest, were associated with synovitis in the posterior GH joint (P < .05). All ROM measures were associated with synovitis in the posterior and inferior GH joint (|r| > 0.20; P < .05 for both). The strength of the supraspinatus and the infraspinatus was associated with synovitis in the posterior GH joint (P < .05). Shoulder function was associated with synovitis in the posterior and inferior GH joint and more in the posterior GH joint (P < .05 for both). Synovitis in the SA space was not associated with any of the clinical parameters. Conclusion: Synovitis in the posterior GH joint was the most severe form of synovitis in the GH joint in patients with a full-thickness RCT. Synovitis in the posterior GH joint was closely associated with increased pain and decreased ROM, muscle strength, and functional score. Synovitis in the SA space was milder and not associated with any clinical parameters.

Minimal Cube Explant Provides Optimal Isolation Condition of Mesenchymal Stem Cells from Umbilical Cord.

BACKGROUND: Enzymatic digestion and explant method have been widely used for isolating umbilical cord-derived mesenchymal stem cells (UC MSCs), although there is still a strong need for robust protocols for optimal isolation for large-scale stem cell banks. This study aims to establish an explant method for clinical scale production of MSCs from human UC tissue and to characterize UC MSCs isolated and cultured with the explant method. METHODS: UC MSCs were isolated by enzymatic digestion, minimal cube explant (MCE) 1-2, MCE 2-4, and MCE 10 and cultured, respectively. Also, human antibody array and basic fibroblast growth factor (bFGF) secretion in conditioned medium (CM) was analyzed. The cells were evaluated initial cell number, colony forming unit-fibroblast (CFU-F), proliferation capacity, CD marker expression, and multi-lineage differentiation. SA-ß-gal assay as well as expression of p16, p21 and p53 was performed by RT-PCR. RESULTS: MCE 2-4 is the most optimized method for isolation of small umbilical cord-derived fast proliferating cells (smumf cells) with the greatest number. MCE 2-4 had the highest secretion of various bioactive factors including bFGF. The MCE 2-4 provided significantly higher CD146 expression than enzymatic digestion, and that expression was maintained until P20. The gene expression of p16, p21, and p53 of smumf cells did not change until P10 and SA-ß-gal activity did not increase until P14. CONCLUSION: This study demonstrated that MCE 2-4 provided an optimal environment to isolate MSCs with quantity and quality from human whole UC tissue through secretion of various bioactive factors inherent to UC.

Arthroscopic supraspinatus advancement for retracted rotator cuff tears: a technical note.

Irreparable rotator cuffs with retracted torn ends remain a significant challenge for most shoulder surgeons. Since repairs are preferable to reconstruction or replacement whenever possible, studies for anatomical reductions with minimal tension and secure fixation are important. In this study, the authors introduce an arthroscopic supraspinatus advancement (ASSA) procedure for retracted rotator cuff tears that could not be adequately reduced to the original footprint. Using modified long, narrow, curved Cobb elevators, procedures can be performed through lateral portals without any additional skin incision. Following meticulous stepwise three-compartment elevation procedures based on the supraspinatus insertion anatomy, the supraspinatus muscle could be safely elevated from the fossa and sufficiently advanced laterally. The authors suggest that ASSA could be a useful procedure for management of challenging retracted rotator cuff tears by maximizing lateral excursions that could convert irreparable tears to reparable tears in select patients.

Effect of Quality of Repair on Clinical and Structural Outcomes of Rotator Cuff Repair.

BACKGROUND: Anatomic repair of a torn rotator cuff tendon on the greater tuberosity (GT) is an important surgical goal in rotator cuff repair. However, few studies have investigated whether the efforts made to maximize coverage of the GT are associated with the clinical and structural outcomes after rotator cuff repair surgery. PURPOSE: To investigate whether the quality of repair at the time of surgery is associated with clinical and structural outcomes after surgery and to identify factors influencing the quality of repair. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Data were retrospectively collected from 141 patients who underwent arthroscopic rotator cuff repair between 2008 and 2016. All repairs were classified according to the amount of postoperative GT coverage: A, complete coverage of the GT (n = 96); B, incomplete coverage, comprising more than half of GT (n = 27); C, incomplete coverage, comprising less than half of the GT (n = 16); and D, exposure of the glenohumeral joint (n = 2). All patients underwent magnetic resonance imaging 1 year after surgery. Clinical outcomes and structural integrity based on Sugaya classification were assessed 2 years and 1 year after surgery, respectively. Preoperative factors associated with the postoperative GT coverage (measured at the close of surgery) were identified using a multivariable proportional odds cumulative logit model. RESULTS: The forward flexion strength in group A (10.3 ± 4.6 lb) was significantly greater than that in group C (6.5 ± 3.7 lb) (P = .003) 2 years after surgery. The postoperative Constant score in group A (76.6 ± 11.5) was greater than that in group C (66.7 ± 15.6) (P = .018). The number of cases that showed retearing of the repaired tendon was as follows: group A (5/96; 5.2%), group B (7/27; 25.9%), and group C (10/16; 62.5%). There was no significant difference in the changes of pain visual analog scale scores among groups 2 years after surgery (all P > .05). Also, there was no significant difference in the changes of range of motion in all directions among groups 2 years after surgery (all P > .05). Patients with preoperative GT coverage B included in the postoperative GT coverage groups through surgery were as follows: group A (23/45; 51.1%), group B (17/45; 37.8%), and group C (5/45; 11.1%). Preoperative GT coverage was the only independent factor that was associated with GT coverage in multivariable analysis. CONCLUSION: Quality of repair, measured as the extent of postoperative GT coverage at the time of surgery, was associated with clinical and structural outcomes after rotator cuff repair surgery.

Florid Reactive Periostitis of the Clavicle: A Case Report.

Florid reactive periostitis (FRP) is a rare benign fibro-osseous proliferation, occurring mostly in the short tubular bones of hands and rarely in the long tubular bones. We report a surgically confirmed case of FRP involving the clavicle in a 26-year-old male. On MRI scans, a soft tissue mass with T2 high signal intensity was found that originated from the periosteum of the clavicle and included surrounding a periosteal elevation and perilesional soft tissue edema. Strong contrast enhancement was noted inside the mass and along the periosteum involving more than half of the circumference of the clavicle. Serial radiographs revealed a soft tissue mass without mineralization that turned into an ossified mass with a solid periosteal reaction within a month.

Accuracy of intra-articular injection of the glenohumeral joint: a modified anterior approach.

PURPOSE: This study examined the accuracy of our modified anterior approach to the glenohumeral joint using arthrography. METHODS: Two hundred fifty-six consecutive patients with adhesive capsulitis received the glenohumeral joint injection: a mixture of 1 mL of 40 mg of triamcinolone hexacetonide, 2 mL of 2% lidocaine, 3 mL of contrast medium (Ioxitalamate), and 4 mL of normal saline solution, for a total of 10 mL, through a modified anterior approach. Anteroposterior, lateral, and axial arthrography after each injection was performed to determine the accuracy and patterns of the injection. The injection was judged to be successful if some of the contrast medium was placed within the joint. RESULTS: There were 78 male and 178 female patients, and the mean age was 54 years (range, 28 to 87 years). In 232 of the 256 patients (90.6%), the injection was deemed to have reached the glenohumeral joint, and these cases were considered successful. Among these patients, the contrast medium was shown only in the joint in 189 (73.8%), whereas in 43 (16.8%) it was shown both in and out of the joint. Of the 24 misguided injections, 15 (5.9%) had anterior placement, 6 (2.3%) had posterior placement, and 2 (0.8%) had superior placement, whereas the material was located in all portions outside the joint in 1 (0.4%). CONCLUSIONS: This study showed that our modified anterior approach had an accuracy greater than 90% for the intra-articular injection of the glenohumeral joint without radiographic guidance.