Intramuscular Brown Fat Activation Decreases Muscle Atrophy and Fatty Infiltration and Improves Gait After Delayed Rotator Cuff Repair in Mice

2020 ◽  
Vol 48 (7) ◽  
pp. 1590-1600 ◽  
Author(s):  
Zili Wang ◽  
Xuhui Liu ◽  
Kunqi Jiang ◽  
Hubert Kim ◽  
Shingo Kajimura ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Muscle Atrophy ◽  
Fatty Infiltration ◽  
Tendon Repair ◽  
Muscle Quality ◽  
Adrenergic Agonists ◽  
Wild Type ◽  
Reporter Mice ◽  
White Fat ◽  
Dependent Mechanism

Background: Successful repair of large and massive rotator cuff (RC) tears remains a challenge at least partially because of secondary muscle atrophy and fatty infiltration. β3 Adrenergic agonists are a group of drugs that promote fat resorption through “white fat browning” of intramuscular stem cells. Purpose: To test the role of a β3 adrenergic receptor agonist, amibegron, in improving muscle quality and forelimb function in a delayed RC repair model via promoting brown/beige adipose tissue activation. Study Design: Controlled laboratory study. Methods: Three-month-old PDGFRα-GFP reporter mice, wild type C57BL/6J mice, and uncoupling protein 1 (UCP-1) knockout mice underwent unilateral supraspinatus tendon transection with a 6-week delayed tendon repair. Animals with sham surgery served as controls. Amibegron was given either immediately after tendon transection or after repair. Gait analysis was conducted to measure forelimb function at 6 weeks after tendon repair. Animals were sacrificed at 6 weeks after repair. Supraspinatus muscles were harvested and analyzed histologically. Reverse transcription polymerase chain reaction was performed to quantify gene expression related to atrophy, fibrosis, and fatty infiltration. Results: Histology of PDGFRα reporter mice showed significantly increased UCP-1 expression, suggesting white fat browning in muscle after RC repair. As administered either immediately after tendon transection or after tendon repair, amibegron significantly reduced muscle atrophy and fatty infiltration and resumed normal upper extremity gait in wild type mice. However, the effect of amibegron was not present in UCP-1 knockout mice, suggesting that the effect of amibegron in treating RC muscle atrophy and fatty infiltration is through a UCP 1–dependent mechanism. Conclusion: Amibegron reduced muscle atrophy and fatty infiltration and improved forelimb function after delayed RC repair through a UCP 1–dependent mechanism. This may be an effective clinical treatment strategy for patients to improve muscle quality after RC repair. Clinical Relevance: β3 Adrenergic agonists may serve as a new pharmacologic modality to treat RC muscle atrophy and fatty infiltration to improve clinical outcome of RC repair.

scholarly journals Effect of Muscle Quality on Operative and Nonoperative Treatment of Rotator Cuff Tears

2019 ◽  
Vol 7 (8) ◽  
pp. 232596711986301
Author(s):  
Micah Naimark ◽  
Thai Trinh ◽  
Christopher Robbins ◽  
Bridger Rodoni ◽  
James Carpenter ◽  
...  
Keyword(s):  
Cohort Study ◽  
Rotator Cuff ◽  
Muscle Atrophy ◽  
Fatty Infiltration ◽  
Nonoperative Treatment ◽  
Nonsurgical Treatment ◽  
Muscle Quality ◽  
Rotator Cuff Tears ◽  
The Impact ◽  
Surgical Group

Background: Rotator cuff muscle atrophy and fatty infiltration are predictors of negative outcomes after rotator cuff repair. However, the impact of muscle degeneration on nonsurgical treatment is unknown. Hypothesis: Rotator cuff muscle atrophy and fatty infiltration will reduce the outcomes of operative repair while having a minimal effect on nonsurgical treatment. Additionally, in the setting of atrophy and fatty infiltration, surgical and nonsurgical treatment will produce equivalent outcomes. Study Design: Cohort study; Level of evidence, 2. Methods: Patients undergoing operative and nonoperative treatment of full-thickness rotator cuff tears were prospectively enrolled into a nonrandomized cohort study. Muscle quality was assessed on magnetic resonance imaging by use of the supraspinatus tangent sign, Warner atrophy, and Goutallier fatty infiltration classifications. Grading was performed by 2 independent observers who were blinded to patient treatment and outcomes. Normalized Western Ontario Rotator Cuff (WORC) index was the primary patient-reported outcome. Multivariate linear regression analysis was used to determine the impact of muscle quality on treatment outcomes. Results: The cohort consisted of 157 patients, 89 (57%) surgical and 68 (43%) nonsurgical, with a mean follow-up of 2.4 years (range, 1-5 years). Tangent sign had the best inter- and intrarater reliability, with kappa statistics of 0.81 and 0.86, respectively. Reliability for Warner atrophy was 0.69 to 0.76 and for Goutallier classification was 0.54 to 0.64. Overall, improvement in WORC scores was higher in the surgical group than the nonsurgical group (39.3 vs 21.2; P < .001). A positive tangent sign was the only independent predictor ( P < .01) of worse outcomes in the surgical group, accounting for an estimated 22-point lower improvement in WORC scores. Conclusion: A positive tangent sign was predictive of worse operative outcomes, resulting in equivalent improvements between surgical and nonsurgical treatment. The tangent sign is a reliable, prognostic indicator that clinicians can use when counseling patients on the optimal treatment of rotator cuff tears.

scholarly journals Muscle Degeneration Induced by Sequential Release and Denervation of the Rotator Cuff Tendon in Sheep

2021 ◽  
Vol 9 (8) ◽  
pp. 232596712110253
Author(s):  
Karl Wieser ◽  
Florian Grubhofer ◽  
Anita Hasler ◽  
Tobias Götschi ◽  
Silvan Beeler ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Muscle Atrophy ◽  
Fatty Infiltration ◽  
Tendon Repair ◽  
Suprascapular Nerve ◽  
Muscle Volume ◽  
Nerve Lesion ◽  
Tendon Tear ◽  
Sequential Release ◽  
Magnetic Resonance Imaging Mri

Background: In a sheep rotator cuff model, tenotomy predominantly induces fatty infiltration, and denervation induces mostly muscle atrophy. In clinical practice, myotendinous retraction after tendon tear or lateralization after tendon repair tear may lead to traction injury of the nerve. Purpose/Hypothesis: To analyze whether an additional nerve lesion during rotator cuff repair leads to further degeneration of the rotator cuff muscle in the clinical setting. We hypothesized that neurectomy after tendon tear would increase atrophy as well as fatty infiltration and that muscle paralysis after neurectomy would prevent myotendinous retraction after secondary tendon release. Study Design: Controlled laboratory study. Methods: Twelve Swiss alpine sheep were used for this study. For the 6 sheep in the tenotomy/neurectomy (T/N) group, the infraspinatus tendon was released; 8 weeks later, the suprascapular nerve was transected. For the 6 sheep in the neurectomy/tenotomy (N/T) group, neurectomy was performed, and the infraspinatus was tenotomized 8 weeks later. All sheep were sacrificed after 16 weeks. Magnetic resonance imaging (MRI) was performed before the first surgery (baseline) and then after 8 and 16 weeks. The MRI data were used to assess muscle volume, fat fraction, musculotendinous retraction, pennation angle, and muscle fiber length of the infraspinatus muscle. Results: Three sheep (2 in the T/N and 1 in the N/T group) had to be excluded because the neurectomy was incomplete. After 8 weeks, muscle volume decreased significantly less in the T/N group (73% ± 2% of initial volume vs 52% ± 7% in the N/T group; P < .001). After 16 weeks, the mean intramuscular fat increase was higher in the T/N group (36% ± 9%) than in the N/T group (23% ± 6%), without reaching significance ( P = .060). After 16 weeks, the muscle volumes of the N/T (52% ± 8%) and T/N (49% ± 3%) groups were the same ( P = .732). Conclusion: Secondary neurectomy after tenotomy of a musculotendinous unit increases muscle atrophy. Tenotomy of a denervated muscle is associated with substantial myotendinous retraction but not with an increase of fatty infiltration to the level of the tenotomy first group. Clinical Relevance: Substantial retraction, which is associated with hitherto irrecoverable fatty infiltration, should be prevented, and additional neurogenic injury during repair should be avoided to limit the development of further atrophy.

scholarly journals Do Outcomes of Arthroscopic Subscapularis Tendon Repairs Depend on Rotator Cuff Fatty Infiltration?

2020 ◽  
Vol 8 (4) ◽  
pp. 232596712091303
Author(s):  
Emily J. Monroe ◽  
Sergio E. Flores ◽  
Alan L. Zhang ◽  
Brian T. Feeley ◽  
Drew A. Lansdown ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Patient Reported Outcomes ◽  
Fatty Infiltration ◽  
Tendon Repair ◽  
Muscle Quality ◽  
Subscapularis Tendon ◽  
Infraspinatus Muscle ◽  
Patient Reported ◽  
Infraspinatus Tendon

Background: Rotator cuff fatty infiltration has been correlated with poorer radiographic and clinical outcomes in supraspinatus and infraspinatus tendon repairs, but this has not been well-studied in subscapularis tendon repairs. Purpose: To evaluate the influence of preoperative rotator cuff fatty infiltration on postoperative outcomes for patients undergoing arthroscopic subscapularis tendon repair. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent arthroscopic subscapularis repair between 2010 and 2016 were retrospectively identified, and demographic data and surgical findings were recorded. The extent of fatty infiltration was determined on preoperative magnetic resonance imaging by the Fuchs modification of the Goutallier classification. At the most recent follow-up, patients completed the Patient-Reported Outcomes Measurement Information System for Upper Extremity (PROMIS-UE) computer adaptive test and a postoperative visual analog scale for pain. The distribution of fatty infiltration was compared between patients undergoing subscapularis tendon repair versus subscapularis tendon repair combined with a posterior cuff repair. Outcomes were compared for patients using Goutallier grade 0-1 versus grade ≥2 changes in each rotator cuff muscle. Multivariate linear regression analysis was performed to evaluate the influence of muscle quality, as well as demographic factors, on PROMIS-UE scores. Significance was defined as P < .05. Results: There were 140 shoulders included (mean age, 61.8 years; 42.1% female; mean follow-up, 51.7 months). The prevalence of Goutallier grade 2 changes or higher was significantly greater in patients with multitendon repair relative to isolated subscapularis tendon repair. For the overall group of all patients undergoing subscapularis tendon repair, whether in isolation or as part of a multitendon repair, PROMIS-UE scores were significantly lower for patients with infraspinatus muscle grade 2 or higher Goutallier changes relative to grade 0 or 1. After adjustment for age, body mass index, patient sex, and fatty infiltration in other rotator cuff muscles, poor infraspinatus muscle quality remained the only significant predictor for lower PROMIS-UE scores. Conclusion: Patients undergoing arthroscopic subscapularis tendon repair with poor infraspinatus muscle quality had worse patient-reported outcomes. This was true whether subscapularis tendon repair was isolated or was performed in conjunction with supraspinatus and infraspinatus tendon repairs.

Rotator Cuff Fatty Infiltration and Muscle Atrophy: Relation to Glenoid Deformity in Primary Glenohumeral Osteoarthritis

2021 ◽  
Author(s):  
Michael A. Moverman ◽  
Richard N. Puzzitiello ◽  
Mariano E. Menendez ◽  
Nicholas R. Pagani ◽  
Paul-Anthony J. Hart ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Muscle Atrophy ◽  
Fatty Infiltration ◽  
Glenohumeral Osteoarthritis

Does successful rotator cuff repair improve muscle atrophy and fatty infiltration of the rotator cuff?

2014 ◽  
Vol 23 (5) ◽  
pp. 604
Author(s):  
Noritaka Hamano ◽  
Atsushi Yamamoto ◽  
Tsutomu Kobayashi ◽  
Hitoshi Shitara ◽  
Tsuyoshi Ichinose ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Muscle Atrophy ◽  
Rotator Cuff Repair ◽  
Fatty Infiltration ◽  
Cuff Repair

scholarly journals Fatty Infiltration Is a Prognostic Marker of Muscle Function After Rotator Cuff Tear

2018 ◽  
Vol 46 (9) ◽  
pp. 2161-2169 ◽  
Author(s):  
Ana P. Valencia ◽  
Jim K. Lai ◽  
Shama R. Iyer ◽  
Katherine L. Mistretta ◽  
Espen E. Spangenburg ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Muscle Atrophy ◽  
Muscle Function ◽  
Contractile Function ◽  
Isometric Force ◽  
Fatty Infiltration ◽  
Collagen Content ◽  
Strongly Correlated ◽  
Computed Tomography Scanning ◽  
Maximal Isometric Force

Background: Massive rotator cuff tears (RCTs) begin as primary tendon injuries and cause a myriad of changes in the muscle, including atrophy, fatty infiltration (FI), and fibrosis. However, it is unclear which changes are most closely associated with muscle function. Purpose: To determine if FI of the supraspinatus muscle after acute RCT relates to short-term changes in muscle function. Study Design: Controlled laboratory study. Methods: Unilateral RCTs were induced in female rabbits via tenotomy of the supraspinatus and infraspinatus. Maximal isometric force and rate of fatigue were measured in the supraspinatus in vivo at 6 and 12 weeks after tenotomy. Computed tomography scanning was performed, followed by histologic analysis of myofiber size, FI, and fibrosis. Results: Tenotomy resulted in supraspinatus weakness, reduced myofiber size, FI, and fibrosis, but no differences were evident between 6 and 12 weeks after tenotomy except for increased collagen content at 12 weeks. FI was a predictor of supraspinatus weakness and was strongly correlated to force, even after accounting for muscle cross-sectional area. While muscle atrophy accounted for the loss in force in tenotomized muscles with minimal FI, it did not account for the greater loss in force in tenotomized muscles with the most FI. Collagen content was not strongly correlated with maximal isometric force, even when normalized to muscle size. Conclusion: After RCT, muscle atrophy results in the loss of contractile force from the supraspinatus, but exacerbated weakness is observed with increased FI. Therefore, the level of FI can help predict contractile function of torn rotator cuff muscles. Clinical Relevance: Markers to predict contractile function of RCTs will help determine the appropriate treatment to improve functional recovery after RCTs.

MRI quantification of fatty infiltration and muscle atrophy in a mouse model of rotator cuff tears

2012 ◽  
Vol 31 (3) ◽  
pp. 421-426 ◽  
Author(s):  
Sanjum P. Samagh ◽  
Erik J. Kramer ◽  
Gerd Melkus ◽  
Dominique Laron ◽  
Blake M. Bodendorfer ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Mouse Model ◽  
Muscle Atrophy ◽  
Fatty Infiltration ◽  
Rotator Cuff Tears
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