SSP Muscle Research Articles

Allogenic Myocytes and Mesenchymal Stem Cells Partially Improve Fatty Rotator Cuff Degeneration in a Rat Model.

Rotator cuff (RC) tears result not only in functional impairment but also in RC muscle atrophy, muscle fattening and eventually to muscle fibrosis. We hypothesized that allogenic bone marrow derived mesenchymal stem cells (MSC) and myocytes can be utilized to improve the rotator cuff muscle fattening and increase the atrophied muscle mass in a rat model. The right supraspinatus (SSP) tendons of 105 inbred rats were detached and muscle fattening was provoked over 4weeks; the left side remained untouched (control group). The animals (n = 25) of the output group were euthanized after 4weeks for reference purposes. The SSP-tendon of one group (n = 16) was left unoperated to heal spontaneously. The SSP-tendons of the remaining 64 rats (4 groups with n = 16) were repaired with transosseous sutures. One group received a saline solution injection in the SSP muscle belly, two other groups received 5 × 106 allogenic myocytes and 5 × 106 allogenic MSC injections from donor rats, respectively, and one group received no additional treatment. After 4weeks of healing, the supraspinatus muscle mass was compared quantitatively and histologically to all the treated groups and to the untreated contralateral side. In the end of the experiments at week 8, the myocyte and MCS treated groups showed a significantly higher muscle mass with 0.2322g and 0.2257g, respectively, in comparison to the output group (0.1911g) at week 4 with p < 0.05. There was no statistical difference between the repaired, treated, or spontaneous healing groups at week 8. Supraspinatus muscle mass of all experimental groups of the right side was significantly lower compared to the untreated contralateral muscle mass. This defect model shows that the injection of allogenic mycocytes and MSC in fatty infiltrated SSP muscles is better than no treatment and can partially improve the SSP muscle belly fattening. Nevertheless, a full restoration of the degenerated and fattened rotator cuff muscle to its original condition is not possible using myocytes and MSC in this model.

Retained Myogenic Potency of Human Satellite Cells from Torn Rotator Cuff Muscles Despite Fatty Infiltration.

Rotator cuff tears (RCTs) are a common shoulder problem in the elderly that can lead to both muscle atrophy and fatty infiltration due to less physical load. Satellite cells, quiescent cells under the basal lamina of skeletal muscle fibers, play a major role in muscle regeneration. However, the myogenic potency of human satellite cells in muscles with fatty infiltration is unclear due to the difficulty in isolating from small samples, and the mechanism of the progression of fatty infiltration has not been elucidated. The purpose of this study was to analyze the population of myogenic and adipogenic cells in disused supraspinatus (SSP) and intact subscapularis (SSC) muscles of the RCTs from the same patients using fluorescence-activated cell sorting. The microstructure of the muscle with fatty infiltration was observed as a whole mount condition under multi-photon microscopy. Myogenic differentiation potential and gene expression were evaluated in satellite cells. The results showed that the SSP muscle with greater fatty infiltration surrounded by collagen fibers compared with the SSC muscle under multi-photon microscopy. A positive correlation was observed between the ratio of muscle volume to fat volume and the ratio of myogenic precursor to adipogenic precursor. Although no difference was observed in the myogenic potential between the two groups in cell culture, satellite cells in the disused SSP muscle showed higher intrinsic myogenic gene expression than those in the intact SSC muscle. Our results indicate that satellite cells from the disused SSP retain sufficient potential of muscle growth despite the fatty infiltration.

The prospective evaluation of changes in fatty infiltration and shoulder strength in nonsurgically treated rotator cuff tears.

The purpose of this study was to evaluate the relationship of fatty infiltration in rotator cuff muscles and shoulder strength in rotator cuff tears and these changes during nonsurgical treatment. Fifty-three shoulders from 47 patients (mean age: 69.9 years) diagnosed with rotator cuff tears by magnetic resonance imaging (MRI) were treated nonsurgically. The degrees of fatty infiltration in supraspinatus (SSP) and infraspinatus (ISP) muscles were graded by the modified Goutallier classification (grade 0-1, grade 2-3, or grade 4). The isometric strength of the abductors (Abd) and external rotators (ER) were examined with a hand dynamometer. We analyzed the correlation of the modified Goutallier classification in SSP and ISP muscles with the strength of Abd and ER at initial visit. In addition, MRI and strength tests were repeated after 24±6 months, and changes in fatty infiltration and strength were examined. Fatty infiltration of SSP and ISP muscles had a negative correlation with the strengths of Abd and ER at initial visit, respectively. Six of 45 shoulders (SSP grade: 0-3) and 7 of 43 shoulders (ISP grade: 0-3) had progression of fatty infiltration. Predictive factor of a progression of fatty infiltration during follow-up was decreased initial strength of Abd. There was no significant change in the strength of Abd, and the strength of ER showed significant improvement between the initial and post-treatment measurements. Even in the subgroup that had progression of fatty infiltration at follow-up, the strength of Abd and ER did not decrease significantly. Although fatty infiltration of the rotator cuff muscles exhibited a negative correlation with muscle strength, fatty infiltration and muscle weakness did not progress at the same rate.

Paper #39 - Reduced muscle degeneration and decreased fatty infiltration after rotator cuff tear in a PARP-1 knock-out mouse model

Introduction: Disturbed muscular architecture, fatty infiltration and muscular atrophy remain irreversible in chronic rotator cuff tears (RCT) even after repair. Poly-[ADP-ribose]-polymerase 1 (PARP1), a nuclear factor involved in DNA damage repair, has shown to be a key element in the up-regulation of early muscle inflammation, atrophy and fat deposition. We therefore hypothesized that the absence of PARP1 would lead to a reduction in muscular architectural damage, early inflammation, atrophy and fatty infiltration subsequent to combined tenotomy and neurotomy in a PARP1 knock-out mouse model. Methods: PARP1 knock-out (KO group) and standard wild type C57BL/6 (WT group) mice were randomly allocated into three different time points (1, 6 and 12 weeks, total n = 72). In all mice the supraspinatus (SSP) and infraspinatus (ISP) tendons of the left shoulder were detached and the SSP muscle was denervated according to a recently established model. Macroscopic muscle weight analysis, retraction documentation using macroscopic suture, magnetic resonance imaging, immunohistochemistry gene expression analysis using real time qPCR (RTqPCR) and histology were used to assess the differences in muscle architecture, early inflammation, fatty infiltration and atrophy between knock out and wild type mice in the supraspinatus muscle. Results: The SSP did retract in both groups, however; the KO muscles and tendons retracted less than the WT muscles (2.1 ± .21 mm vs 3.4 ± .41 mm;P = .02). Further assessment of muscle architecture demonstrated that the pennation angle was significantly lower in the KO groups at 6 and 12 weeks (28 ± 5 vs 36 ± 5 and 29 ± 4 vs 34 ± 3; P < .0001). Combined Tenotomy and neurotomy resulted in a significant loss of muscle mass in both groups compared to the contralateral unoperated side (KO group 62 ± 11% and WT group 52 ± 11%, P = .04) at 6 weeks. But at 12 weeks postoperatively, there was a significant increase in muscle mass to near normal levels in KO group compared to the WT group (14 ± 6% and 42 ± 7% lower muscle mass respectively; P < .0001). Immunohistochemistry revealed a significant decrease in the expression of inflammatory, apoptotic, adipogenic and muscular atrophy genes at both the 1 week and 6 weeks time points, but not at 12 weeks in the KO group compared to the WT group. This was confirmed by histology. Discussion: Our study is the first to show that knocking out PARP1 leads to decreased loss of muscle architecture, early inflammation, fatty infiltration and atrophy after combined tenotomy and neurotomy of the rotator cuff muscle. Although KO and WT mice developed severe atrophy and fatty infiltration 6 weeks after surgery, the muscles of the KO mice regenerated to almost normal size after 12 weeks. We conclude that PARP1 has an influence on the muscular deterioration after RCT.

Quantitative Shear-Wave US Elastography of the Supraspinatus Muscle: Reliability of the Method and Relation to Tendon Integrity and Muscle Quality.

To evaluate the reliability of ultrasonographic (US) elastography of the supraspinatus (SSP) muscle, define normal shear-wave velocity (SWV) values, and correlate findings with tendon integrity and muscle quality. The study was approved by the local ethics committee, and written informed consent was obtained from all patients. SSP SWV (in meters per second) was prospectively assessed twice in 22 asymptomatic volunteers (mean age ± standard deviation, 53.8 years ± 15.3; 11 women and 11 men) by two independent examiners by using shear-wave elastography. Forty-four patients (mean age, 51.9 years ± 15.0; 22 women and 22 men) were prospectively included. SWV findings were compared with tendon integrity, tendon retraction (Patte classification), fatty muscle infiltration (Goutallier stages 0-IV), and muscle volume atrophy (tangent sign) on magnetic resonance (MR) images. Descriptive statistics, Spearman correlation, analysis of variance, two-sample t test, and intraclass correlation coefficient (ICC) were used. Test-retest reliability for mean total SWV (MTSWV) was good for examiner 1 (ICC = 0.70; 95% confidence interval [CI]: 0.30, 0.87; P = .003) and excellent for examiner 2 (ICC = 0.80; 95% CI: 0.53, 0.92; P < .001). Interexaminer reliability was excellent (ICC = 0.89; 95% CI: 0.64, 0.96; P < .001). MTSWV in volunteers (3.0 m/sec ± 0.5) was significantly higher than that in patients (2.5 m/sec ± 0.5; P = .001). For tendon integrity, no significant difference in MTSWV was found. For tendon retraction, MTSWV varies significantly between patients with different degrees of retraction (P = .047). No significant differences were found for Goutallier subgroups. MTSWV was significantly lower with a positive tangent sign (P = .015; n = 10). Shear-wave elastography is reproducible for assessment of the SSP muscle. Mean normal SSP SWV is 3.0 m/sec ± 0.5. SWV decreases with increasing fat content (Goutallier stage 0-III) and increases in the final stage of fatty infiltration (Goutallier stage IV).

Quantitative assessment of rotator cuff muscle elasticity: Reliability and feasibility of shear wave elastography

Ultrasound imaging has been used to evaluate various shoulder pathologies, whereas, quantification of the rotator cuff muscle stiffness using shear wave elastography (SWE) has not been verified. The purpose of this study was to investigate the reliability and feasibility of SWE measurements for the quantification of supraspinatus (SSP) muscle elasticity. Thirty cadaveric shoulders (18 intact and 12 with torn rotator cuff) were used. Intra- and inter-observer reliability was evaluated on an established SWE technique for measuring the SSP muscle elasticity. To assess the effect of overlying soft tissues above the SSP muscle, SWE values were measured with the transducer placed on the skin, on the subcutaneous fat after removing the skin, on the trapezius muscle after removing the subcutaneous fat, and directly on the SSP muscle. In addition, SWE measurements on 4 shoulder positions (0°, 30°, 60°, and 90° abduction) were compared in those with/without rotator cuff tears. Intra- and inter-observer reliability of SWE measurements were excellent for all regions in SSP muscle. Also, removing the overlying soft tissue showed no significant difference on SWE values measured in the SSP muscle. The SSP muscle with 0° abduction showed large SWE values, whereas, shoulders with large-massive tear showed smaller variation throughout the adduction–abduction positions. SWE is a reliable and feasible tool for quantitatively assessing the SSP muscle elasticity. This study also presented SWE measurements on the SSP muscle under various shoulder abduction positions which might help characterize patterns in accordance to the size of rotator cuff tears.

Intramuscular fat accumulation and muscle atrophy in the absence of muscle retraction.

ObjectivesAlthough many clinical and experimental investigations have shed light on muscle atrophy and intramuscular accumulation of fat after rotator cuff disruption, none have reported on their onset in the absence of muscle retraction.MethodsIn 30 rabbits, we detached one supraspinatus (SSP) tendon and repaired it immediately, thus preventing muscle retraction. The animals were killed in groups of 10 at one, two and six weeks. Both shoulders of 15 non-operated rabbits served as controls. We measured the weight and volume of SSP muscles and quantified the cross-sectional area of intramuscular fat (i-fat) histologically.ResultsThere was significant loss of muscle weight and volume after one week (p = 0.004 and 0.003, respectively), and two weeks (both p < 0.001) in the experimental group; which recovered to control values after six weeks. I-fat accumulated one week after immediate repair, greater than in the control group and statistically significant at the mid-part of the muscle (mean 2.7% vs 1.5%, p = 0.008). I-fat continued to accumulate up to six weeks at all sites of the SSP muscle (all 3, p < 0.001). More fat accumulated closer to the musculotendinous junction than at the mid-part after two and six weeks (p = 0.012 and 0.019, respectively).ConclusionMuscle atrophy and i-fat accumulation occur early after SSP tendon tear and immediate repair. While early repair benefitted muscle recovery, it did not prevent fat accumulation. SSP muscle retraction was not essential to the muscle alterations. The divergent evolution of muscle and fat points to different pathophysiologies.

Possible involvement of IGF-1 signaling on compensatory growth of the infraspinatus muscle induced by the supraspinatus tendon detachment of rat shoulder.

A rotator cuff tear (RCT) is a common musculoskeletal disorder among elderly people. RCT is often treated conservatively for functional compensation by the remaining muscles. However, the mode of such compensation after RCT has not yet been fully understood. Here, we used the RCT rat model to investigate the compensatory process in the remaining muscles. The involvement of insulin‐like growth factor 1 (IGF‐1)/Akt signaling which potentially contributes to the muscle growth was also examined. The RCT made by transecting the supraspinatus (SSP) tendon resulted in atrophy of the SSP muscle. The remaining infraspinatus (ISP) muscle weight increased rapidly after a transient decrease (3 days), which could be induced by posttraumatic immobilization. The IGF‐1 mRNA levels increased transiently at 7 days followed by a gradual increase thereafter in the ISP muscle, and those of IGF‐1 receptor mRNA significantly increased after 3 days. IGF‐1 protein levels biphasically increased (3 and 14 days), then gradually decreased thereafter. The IGF‐1 protein levels tended to show a negative correlation with IGF‐1 mRNA levels. These levels also showed a negative correlation with the ISP muscle weight, indicating that the increase in IGF‐1 secretion may contribute to the ISP muscle growth. The pAkt/Akt protein ratio decreased transiently by 14 days, but recovered later. The IGF‐1 protein levels were negatively correlated with the pAkt/Akt ratio. These results indicate that transection of the SSP tendon activates IGF‐1/Akt signaling in the remaining ISP muscle for structural compensation. Thus, the remaining muscles after RCT can be a target for rehabilitation through the activation of IGF‐1/Akt signaling.

Deltoid muscle shape analysis with magnetic resonance imaging in patients with chronic rotator cuff tears

BackgroundIt seems appropriate to assume, that for a full and strong global shoulder function a normally innervated and active deltoid muscle is indispensable. We set out to analyse the size and shape of the deltoid muscle on MR-arthrographies, and analyse its influence on shoulder function and its adaption (i.e. atrophy) for reduced shoulder function.MethodsThe fatty infiltration (Goutallier stages), atrophy (tangent sign) and selective myotendinous retraction of the rotator cuff, as well as the thickness and the area of seven anatomically defined segments of the deltoid muscle were measured on MR-arthrographies and correlated with shoulder function (i.e. active abduction). Included were 116 patients, suffering of a rotator cuff tear with shoulder mobility ranging from pseudoparalysis to free mobility. Kolmogorov-Smirnov test was used to determine the distribution of the data before either Spearman or Pearson correlation and a multiple regression was applied to reveal the correlations.ResultsOur developed method for measuring deltoid area and thickness showed to be reproducible with excellent interobserver correlations (r = 0.814–0.982).The analysis of influencing factors on active abduction revealed a weak influence of the amount of SSP tendon (r = −0.25; p < 0.01) and muscle retraction (r = −0.27; p < 0.01) as well as the stage of fatty muscle infiltration (GFDI: r = −0.36; p < 0.01). Unexpectedly however, we were unable to detect a relation of the deltoid muscle shape with the degree of active glenohumeral abduction. Furthermore, long-standing rotator cuff tears did not appear to influence the deltoid shape, i.e. did not lead to muscle atrophy.ConclusionsOur data support that in chronic rotator cuff tears, there seems to be no disadvantage to exhausting conservative treatment and to delay implantation of reverse total shoulder arthroplasty, as the shape of deltoid muscle seems only to be influenced by natural aging, but to be independent of reduced shoulder motion.

Muscle tissue atrophy, extramuscular and intramuscular fat accumulation, and fat gradient after delayed repair of the supraspinatus tendon: A comparative study in the rabbit

To investigate the atrophy of supraspinatus (SSP) muscle tissue and accumulation of extramuscular fat (e-fat) and intramuscular fat (i-fat) after delayed repair of the SSP tendon, and to correlate CT findings with histology. One SSP tendon of 36 rabbits was transected, then repaired in groups of 12 at 4, 8, or 12 weeks and then followed for 12 weeks. Thirty-six normal shoulders served as controls. We compared the SSP muscle, e-fat weights and volumes, muscle tissue and i-fat areas on histology, e-fat and attenuation values on CT between the experimental and control shoulders. CT-to-histology correlations were run. SSP muscle tissue atrophy, e-fat and i-fat accumulation were present after tendon repair delayed by 4, 8, or 12 weeks (all p < 0.05). Both e-fat and i-fat accumulation presented increasing proximal-to-distal gradients (both p < 0.05). CT depicted the muscle tissue atrophy, e-fat and i-fat accumulation, and increasing proximal-to-distal gradients (all p < 0.05). We found strong CT-to-histology correlations (p < 0.05). SSP muscles showed tissue atrophy, e-fat and i-fat accumulation after successful SSP tendon repairs delayed by 4, 8, or 12 weeks. Subtracting i-fat from the muscle area determined the SSP muscle tissue atrophy. Increasing proximal-to-distal fat gradients were diagnostic if not pathognomonic of an initial SSP tendon disruption.

Using chemical-shift MR imaging to quantify fatty degeneration within supraspinatus muscle due to supraspinatus tendon injuries

The objective of this study was to prospectively quantify the fatty degeneration of supraspinatus (SSP) muscle due to SSP tendon injuries by using chemical-shift magnetic resonance imaging (CS-MRI). Forty-one patients with suspected rotator cuff tear or impingement examined with MR arthrography were included in the study. The following images were obtained after injection of diluted gadolinium chelate into glenohumeral joint: fat-saturated T1-weighted spin echo in the coronal, axial, and sagittal-oblique plane; fat-saturated T2-weighted and intermediate-weighted fast spin-echo in the coronal-oblique plane; and T1-weighted spin echo in the sagittal-oblique plane. CS-MRI was performed in the coronal plane using a double-echo fast low-angle shot (FLASH) sequence. SSP tendon changes were classified as normal, tendinosis, and partial and complete tear according to MR arthrography findings. Fatty degeneration was quantified after measurement of signal intensity values within the region of interest (ROI) placed over SSP muscle. Signal intensity (SI) suppression ratio and SI index were calculated with the values obtained. Degrees of fatty degeneration depicted in normal subjects and subjects with rotator cuff injuries were compared. Median (min:max) was used as descriptive values. SI suppression ratio was -3.5% (-15.5:3.03) in normal subjects, whereas it was -13.5% (-28.55:-6.60), -30.7% (-41.5:-20.35), and -43.75% (-62:-24.90) in tendinosis, partial and complete tears, respectively. SI index was 0.75% (-6:11.5) in normal subjects. It was 10% (4.50:27), 26.5% (19.15:35.5), and 41% (23.9:57) in tendinosis, partial and complete tears, respectively. The increase in degree of fatty degeneration parallels the seriousness of tendon pathology. CS-MRI is a useful method for grading fat accumulation within SSP muscle.

Fatty Atrophy of Supraspinatus and Infraspinatus Muscles: Accuracy of US

To prospectively evaluate the accuracy of ultrasonography (US) in depicting fatty atrophy of the supraspinatus (SSP) and infraspinatus (ISP) muscles, with magnetic resonance (MR) imaging as the reference standard. Institutional review board approval and informed consent were obtained. SSP and ISP muscles of 65 consecutive patients (27 women, 38 men; mean age, 53.1 years; range, 28-83 years) with possible rotator cuff tears were evaluated with US in two planes. Visibility of muscle contour, pennate pattern, the central tendon, and muscle echogenicity was assessed by two radiologists. On the basis of these findings, diagnosis of substantial fatty atrophy was made at US. Accuracy, sensitivity, specificity, proportion of over- and underestimations, and interobserver agreement in diagnosis of substantial (grade 2 or greater) muscle atrophy were determined. Fatty atrophy was graded at MR imaging as follows: score of 0 = no intramuscular fat, score of 1 = some fatty streaks, score of 2 = fat evident but less extensive than muscle, score of 3 = fat equal to muscle, and score of 4 = fat more extensive than muscle. For readers 1 and 2, the accuracy of US in depicting fatty atrophy of SSP muscle was 75% (49 of 65) and 72% (47 of 65), sensitivity was 89% (eight of nine) and 100% (nine of nine), and specificity was 73% (41 of 56) and 68% (38 of 56), respectively. For readers 1 and 2, the accuracy of US in depicting fatty atrophy of ISP muscle was 85% (55 of 65) and 80% (52 of 65), sensitivity was 58% (11 of 19) and 63% (12 of 19), and specificity was 96% (44 of 46) and 87% (40 of 46), respectively. Overestimation of SSP muscle atrophy was more common (23% [15 of 65] for reader 1 and 28% [18 of 65] for reader 2) than underestimation (2% [one of 65] for reader 1 and 0% [0 of 65] for reader 2). For readers 1 and 2, overestimation of ISP muscle atrophy was 3% (two of 65) and 9% (six of 65) and underestimation was 12% (eight of 65) and 9% (seven of 65), respectively. Interobserver agreement was moderate for SSP (kappa = 0.55) and substantial for ISP (kappa = 0.71) muscles. US is moderately accurate in the diagnosis of substantial fatty atrophy of the SSP or ISP muscle.