Characterising 24-h skeletal muscle gene expression alongside metabolic & endocrine responses under diurnal conditions.

CONTEXT: Skeletal muscle plays a central role in the storage, synthesis, and breakdown of nutrients, yet little research has explored temporal responses of this human tissue, especially with concurrent measures of systemic biomarkers of metabolism. OBJECTIVE: To characterise temporal profiles in skeletal muscle expression of genes involved in carbohydrate metabolism, lipid metabolism, circadian clocks, and autophagy and descriptively relate them to systemic metabolites and hormones during a controlled laboratory protocol. METHODS: Ten healthy adults (9M/1F, mean ± SD: age: 30 ± 10 y; BMI: 24.1 ± 2.7 kg·m-2) rested in the laboratory for 37 hours with all data collected during the final 24 hours of this period (i.e., 0800-0800 h). Participants ingested hourly isocaloric liquid meal replacements alongside appetite assessments during waking before a sleep opportunity from 2200-0700 h. Blood samples were collected hourly for endocrine and metabolite analyses, with muscle biopsies occurring every 4 h from 1200 h to 0800 h the following day to quantify gene expression. RESULTS: Plasma insulin displayed diurnal rhythmicity peaking at 1804 h. Expression of skeletal muscle genes involved in carbohydrate metabolism (Name - Acrophase; GLUT4 - 1440 h; PPARGC1A -1613 h; HK2 - 1824 h) and lipid metabolism (FABP3 - 1237 h; PDK4 - 0530 h; CPT1B - 1258 h) displayed 24 h rhythmicity that reflected the temporal rhythm of insulin. Equally, circulating glucose (0019 h), NEFA (0456 h), glycerol (0432 h), triglyceride (2314 h), urea (0046 h), CTX (0507 h) and cortisol concentrations (2250 h) also all displayed diurnal rhythmicity. CONCLUSION: Diurnal rhythms were present in human skeletal muscle gene expression as well systemic metabolites and hormones under controlled diurnal conditions. The temporal patterns of genes relating to carbohydrate and lipid metabolism alongside circulating insulin are consistent with diurnal rhythms being driven in part by the diurnal influence of cyclic feeding and fasting.

Finding Your Job in Orthopaedic Trauma: A Survey Revealing the Cold Hard Facts.

OBJECTIVES: Finding a first job after fellowship can be stressful due to the uncertainty about which resources to use, including fellowship program directors, residency faculty, and other sources. There are more than 90 orthopaedic trauma fellows seeking jobs annually. We surveyed orthopaedic trauma fellows to determine the job search process. DESIGN: An anonymous 37-question survey. SETTING: Online Survey. PATIENT SELECTION CRITERIA: Orthopaedic trauma fellows from the 5 fellowship-cycle years of 2016-2021. OUTCOME MEASURES AND COMPARISONS: The primary questions were related to the job search process, current job, and work details. The secondary questions addressed job satisfaction. Data analysis was performed using STATA 17. RESULTS: There were 159 responses (40%). Most of the respondents completed a fellowship at an academic program (84%). Many (50%) took an academic job and 24% were hospital employed. Sixteen percent had a job secured before fellowship and 49% went on 2-3 interviews. Word of mouth was the top resource for finding a job (53%) compared with fellowship program director (46%) and residency faculty (33%). While 82% reported ending up in their first-choice job, 34% of respondents felt they "settled." The number of trauma cases was important (62%), ranked above compensation (52%) as a factor affecting job choice. Surgeons who needed to supplement their practice (46%) did so with primary and revision total joints (37%). CONCLUSIONS: Jobs were most often found by word of mouth. Most fellows landed their first job choice, but still a third of respondents reporting settling on a job. Case volume played a significant role in factors affecting job choice.

Dorsal Impaction Injuries of the Distal Radius: Operative Technique Through Dorsal Approach to the Wrist.

SUMMARY: Distal radius fractures vary widely in fracture pattern and displacement. Impaction injuries involving the dorsal articular surface of the distal radius can present challenges when anatomic reduction and fixation is attempted through a standard volar approach. Dorsal approach to the distal radius can provide direct visualization of these fracture patterns, greatly facilitating anatomic reduction and stabilization. In this technique video, surgical approach, fracture reduction, and operative fixation of a dorsally impacted, intra-articular distal radius fracture through a dorsal approach is presented. Low-profile dorsal plating can be a safe and effective technique in treating amenable distal radius fractures, with satisfactory radiographic and clinical outcomes. Although this technique provides excellent exposure and facilitates anatomic reduction, surgeons should be aware of associated risks of wrist stiffness and extensor tendon irritation and select low-profile constructs to mitigate these risks.

Single-Incision, Four-Compartment Fasciotomy and Application of Negative Pressure Dressing for Compartment Syndrome of the Leg.

SUMMARY: The video described by this article presents a safe and effective technique for single-incision, 4-compartment fasciotomy of the leg in a patient with a tibial plateau fracture and clinically diagnosed compartment syndrome. We also demonstrate a technique for the application of a negative pressure wound dressing when delayed closure or coverage is planned.

Phosphate Loading Does not Improve 30-km Cycling Time-Trial Performance in Trained Cyclists.

Phosphate is integral to numerous metabolic processes, several of which strongly predict exercise performance (i.e., cardiac function, oxygen transport, and oxidative metabolism). Evidence regarding phosphate loading is limited and equivocal, at least partly because studies have examined sodium phosphate supplements of varied molar mass (e.g., mono/di/tribasic, dodecahydrate), thus delivering highly variable absolute quantities of phosphate. Within a randomized cross-over design and in a single-blind manner, 16 well-trained cyclists (age 38 ± 16 years, mass 74.3 ± 10.8 kg, training 340 ± 171 min/week; mean ± SD) ingested either 3.5 g/day of dibasic sodium phosphate (Na2HPO4: 24.7 mmol/day phosphate; 49.4 mmol/day sodium) or a sodium chloride placebo (NaCl: 49.4 mmol/day sodium and chloride) for 4 days prior to each of two 30-km time trials, separated by a washout interval of 14 days. There was no evidence of any ergogenic benefit associated with phosphate loading. Time to complete the 30-km time trial did not differ following ingestion of sodium phosphate and sodium chloride (3,059 ± 531 s vs. 2,995 ± 467 s). Accordingly, neither absolute mean power output (221 ± 48 W vs. 226 ± 48 W) nor relative mean power output (3.02 ± 0.78 W/kg vs. 3.08 ± 0.71 W/kg) differed meaningfully between the respective intervention and placebo conditions. Measures of cardiovascular strain and ratings of perceived exertion were very closely matched between treatments (i.e., average heart rate 161 ± 11 beats per minute vs. 159 ± 12 beats per minute; Δ2 beats per minute; and ratings of perceived exertion 18 [14-20] units vs. 17 [14-20] units). In conclusion, supplementing with relatively high absolute doses of phosphate (i.e., >10 mmol daily for 4 days) exerted no ergogenic effects on trained cyclists completing 30-km time trials.

Elbow Trauma: An Evidence-Based Approach to Improving Outcomes.

The management of elbow fractures remains difficult and controversial. The failure rate of surgical intervention in elbow fractures remains higher than that seen with other fractures, and there remains significant room for improvement in the care of these injuries. Evidence-based management strategies for elbow fractures and how to prevent and manage complications following elbow fracture surgery have been described.

Recommendations on the use of virtual interviews in the orthopaedic trauma fellowship match: A survey of applicant and fellowship director perspectives.

OBJECTIVE: The aim of this study was to assess applicant and fellowship director (FD) perspectives on virtual interviewing based on the 2019 to 2020 orthopaedic trauma fellowship interview experience and to develop recommendations for future application cycles. METHODS: Web-based surveys were distributed to all matched applicants and orthopaedic trauma FDs after the 2019 and 2020 orthopaedic trauma fellowship match. Thirty-one applicants and 23 FDs completed the survey-response rates of 34% and 38%, respectively. RESULTS: Virtual interviews were completed by 68% of applicants and 17% of FDs. Twenty-nine percent of applicants felt they were able to familiarize themselves with the culture of programs, and 38% of applicants were satisfied with their ability to present themselves. Most (62%) were comfortable ranking programs based on the virtual interview, but 38% reported the format influenced them to rank a program lower. Among all applicants, 77% preferred the in-person interview. Most FDs (75%) reported virtual interviews limited their ability to familiarize themselves with an applicant, and only 50% were comfortable ranking an applicant afterward. Still, 78% of FDs believe there is a role for virtual interviews in the fellowship match. Choosing a virtual interview may negatively affect applicants as 97% of applicants worry the choice conveys less interest to programs, while 43% of FDs would interpret it as less interest. CONCLUSIONS: Virtual interviews have multiple shortcomings but are technically feasible and provide reasonable information to applicants and FDs to complete the match process. Our recommendations, based on the perspectives of applicants and FDs, can guide their implementation.

Retrograde Intramedullary Nail for Distal Femur Fracture, Through a Total Knee Arthroplasty.

SUMMARY: Distal femur fractures are common in the elderly population. The risk of sustaining a distal femur fracture is increased with the presence of total knee arthroplasty components. Fixation with a retrograde intramedullary nail is a viable option for treatment of these injuries. This case-based video demonstrates the preoperative planning, techniques, and potential technical pitfalls to performing a retrograde intramedullary nail through a total knee arthroplasty in patients with a distal femur fracture.

Examination Under Anesthesia for Evaluation of Hip Stability in Posterior Wall Acetabulum Fractures.

Posterior wall fractures of the acetabulum are the most common acetabular fracture pattern. Stable, congruous hips are amenable to nonoperative management, whereas any instability in the hip is an indication for operative management of the posterior wall fracture. Stability cannot adequately be predicted by static imaging alone. Therefore, the dynamic stress examination under anesthesia remains the gold standard in determining hip stability to guide treatment. This case-based video demonstrates a systematic technique for performing an examination under anesthesia and explains how to interpret the fluoroscopic imaging to differentiate stable and unstable hips.

Irrigation and Debridement of an Open Ankle Fracture With Open Reduction and Internal Fixation and Syndesmotic Fixation Using a Suture Button Device.

Ankle fractures are among the most common surgically treated fractures. The incidence of syndesmotic injury in ankle fractures is 13%-20%. The goal of syndesmotic fixation is a stable, symmetric ankle joint. Missing or poorly reducing a syndesmotic injury can result in diminished function and tibiotalar arthritis. Recently, a suture button-type device has been used instead of the traditional trans-syndesmotic screw-type fixation. This case-based video demonstrates a technique for using suture button-type devices to repair syndesmotic ankle injuries and presents the data regarding the outcomes of this novel technique.

Modern Implant Options for the Treatment of Distal Femur Fractures.

Distal femur fractures occur in a periarticular fracture pattern and disproportionately afflict an aging population. Although the goals of treatment have not changed, the emergence of new surgical techniques and devices has recently been developed and refined to treat this challenging fracture pattern. Treatment options include open reduction and internal fixation with periarticular locking plates, intramedullary nails, or distal femur replacement. Despite rapid adoption, these modern solutions display a concerning complication rate, specifically from nonunion and malunion. The indications for each of these treatment strategies are not well defined and are the subject of current debate. As with the use of any orthopaedic implant, the knowledge of the strengths and weaknesses of each construct is paramount to successful treatment of these fractures. Recently, as the understanding of the biomechanics of distal femur fracture healing has improved, the literature has demonstrated clinical and theoretical improvements in the outcomes after distal femur fracture repair.

Inhibition of p38 mitogen-activated protein kinase signaling reduces fibrosis and lipid accumulation after rotator cuff repair.

BACKGROUND: The repair of rotator cuff tears is often complicated by fatty degeneration, which is the combination of lipid accumulation, fibrosis, inflammation, and muscle weakness. A signaling molecule that plays a central role in these processes is p38 mitogen-activated protein kinase (MAPK). The purpose of this study was to evaluate the ability of a small molecule inhibitor of p38 MAPK, SB203580, to reduce fatty degeneration in a preclinical model of rotator cuff injury and repair. MATERIALS AND METHODS: Adult rats underwent a bilateral supraspinatus tenotomy that was repaired 30 days later. Rats were treated with SB203580 or vehicle every 2 days, with injections beginning 3 days before surgery and continuing until 7 days after surgery. Two weeks after surgical repair, muscles were analyzed using histology, lipid profiling, gene expression, and permeabilized muscle fiber contractility. RESULTS: Inhibition of p38 MAPK resulted in a nearly 49% reduction in fat accumulation and a 29% reduction in collagen content, along with changes in corresponding genes regulating adipogenesis and matrix accumulation. There was also a marked 40% to 80% decrease in the expression of several proinflammatory genes, including IL1B, IL6, and COX2, and a 360% increase in the anti-inflammatory gene IL10. No differences were observed for muscle fiber force production. CONCLUSION: Inhibition of p38 MAPK was found to result in a significant decrease in intramuscular lipid accumulation and fibrosis that is usually seen in the degenerative cascade of rotator cuff tears, without having negative effects on the contractile properties of the rotator cuff muscle tissue.

Simvastatin reduces fibrosis and protects against muscle weakness after massive rotator cuff tear.

BACKGROUND: Chronic rotator cuff tears are a common source of shoulder pain and disability, and patients with chronic cuff tears often have substantial weakness, fibrosis, inflammation, and fat accumulation. Identifying therapies to prevent the development of these pathologic processes will likely have a positive impact on clinical outcomes. Simvastatin is a drug with demonstrated anti-inflammatory and antifibrotic effects in many tissues but had not previously been studied in the context of rotator cuff tears. We hypothesized that after the induction of a massive supraspinatus tear, simvastatin would protect muscles from a loss of force production and fibrosis. METHODS: We measured changes in muscle fiber contractility, histology, and biochemical markers of fibrosis and fatty infiltration in rats that received a full-thickness supraspinatus tear and were treated with either carrier alone or simvastatin. RESULTS: Compared with vehicle-treated controls, simvastatin did not have an appreciable effect on muscle fiber size, but treatment did increase muscle fiber specific force by 20%. Simvastatin also reduced collagen accumulation by 50% but did not affect triglyceride content of muscles. Several favorable changes in the expression of genes and other markers of inflammation, fibrosis, and regeneration were also observed. CONCLUSIONS: Simvastatin partially protected muscles from the weakness that occurs as a result of chronic rotator cuff tear. Fibrosis was also markedly reduced in simvastatin-treated animals. Whereas further studies are necessary, statin medication could potentially help improve outcomes for patients with rotator cuff tears.

Reduced muscle fiber force production and disrupted myofibril architecture in patients with chronic rotator cuff tears.

BACKGROUND: A persistent atrophy of muscle fibers and an accumulation of fat, collectively referred to as fatty degeneration, commonly occur in patients with chronic rotator cuff tears. The etiology of fatty degeneration and function of the residual rotator cuff musculature have not been well characterized in humans. We hypothesized that muscles from patients with chronic rotator cuff tears have reduced muscle fiber force production, disordered myofibrils, and an accumulation of fat vacuoles. METHODS: The contractility of muscle fibers from biopsy specimens of supraspinatus muscles of 13 patients with chronic full-thickness posterosuperior rotator cuff tears was measured and compared with data from healthy vastus lateralis muscle fibers. Correlations between muscle fiber contractility, American Shoulder and Elbow Surgeons (ASES) scores, and tear size were analyzed. Histology and electron microscopy were also performed. RESULTS: Torn supraspinatus muscles had a 30% reduction in maximum isometric force production and a 29% reduction in normalized force compared with controls. Normalized supraspinatus fiber force positively correlated with ASES score and negatively correlated with tear size. Disordered sarcomeres were noted, along with an accumulation of lipid-laden macrophages in the extracellular matrix surrounding supraspinatus muscle fibers. CONCLUSIONS: Patients with chronic supraspinatus tears have significant reductions in muscle fiber force production. Force production also correlates with ASES scores and tear size. The structural and functional muscle dysfunction of the residual muscle fibers is independent of the additional area taken up by fibrotic tissue. This work may help establish future therapies to restore muscle function after the repair of chronically torn rotator cuff muscles.

Muscle fibers are injured at the time of acute and chronic rotator cuff repair.

BACKGROUND: Rotator cuff tears are a common source of shoulder pain and disability. Even after surgical repair, some patients continue to have reduced function and progression of fatty degeneration. Because patients with chronic cuff tears often experience muscle shortening, it is possible that repairing the tendon to its anatomic footprint induces a stretch-induced muscle injury that could contribute to failures of the repair and perhaps ongoing pain. QUESTIONS/PURPOSES: We hypothesized that, compared with acutely torn and repaired muscles, the stretch that is required to repair a chronically torn cuff would result in more muscle fiber damage. Specifically, we asked: (1) Is there muscle fiber damage that occurs from repair of an acutely torn rotator cuff and does it vary by location in the muscle; and (2) is the damage greater in the case of repair of a chronic injury? METHODS: We used an open surgical approach to create a full-thickness rotator cuff tear in rats, and measured changes in muscle mass, length, and the number of fibers containing the membrane impermeable Evans Blue Dye after acute (1 day) or chronic (28 days) cuff tear or repair in rats. Differences between groups were tested using a one-way ANOVA followed by Tukey's post hoc sorting. RESULTS: Chronic tears resulted in 24% to 35% decreases in mass and a 20% decrease in length. The repair of acutely and chronically torn muscles resulted in damage to 90% of fibers in the distal portion of the muscle. In the proximal portion, no differences between the acutely torn and repaired groups and controls were observed, whereas repairing the chronically torn group resulted in injury to almost 70% of fibers. CONCLUSIONS: In a rat model, marked injury to muscle fibers is induced when the tendons of torn rotator cuffs are repaired to their anatomic footprint. CLINICAL RELEVANCE: In this animal model, we found that repair of chronically torn cuff muscles results in extensive injury throughout the muscle. Based on these findings, we posit that inducing a widespread injury at the time of surgical repair of chronically torn rotator cuff muscles may contribute to the problems of failed repairs or continued progression of fatty degeneration that is observed in some patients that undergo rotator cuff repair. Therapeutic interventions to protect muscle fiber membranes potentially could enhance outcomes for patients undergoing rotator cuff repair. To evaluate this, future studies that evaluate the use of membrane sealing compounds or drugs that upregulate endogenous membrane-sealing proteins are warranted.

Inhibition of 5-LOX, COX-1, and COX-2 increases tendon healing and reduces muscle fibrosis and lipid accumulation after rotator cuff repair.

BACKGROUND: The repair and restoration of function after chronic rotator cuff tears are often complicated by muscle atrophy, fibrosis, and fatty degeneration of the diseased muscle. The inflammatory response has been implicated in the development of fatty degeneration after cuff injuries. Licofelone is a novel anti-inflammatory drug that inhibits 5-lipoxygenase (5-LOX), as well as cyclooxygenase (COX)-1 and COX-2 enzymes, which play important roles in inducing inflammation after injuries. While previous studies have demonstrated that nonsteroidal anti-inflammatory drugs and selective inhibitors of COX-2 (coxibs) may prevent the proper healing of muscles and tendons, studies about bone and cartilage have demonstrated that drugs that inhibit 5-LOX concurrently with COX-1 and COX-2 may enhance tissue regeneration. HYPOTHESIS: After the repair of a chronic rotator cuff tear in rats, licofelone would increase the load to failure of repaired tendons and increase the force production of muscle fibers. STUDY DESIGN: Controlled laboratory study. METHODS: Rats underwent supraspinatus release followed by repair 28 days later. After repair, rats began a treatment regimen of either licofelone or a vehicle for 14 days, at which time animals were euthanized. Supraspinatus muscles and tendons were then subjected to contractile, mechanical, histological, and biochemical analyses. RESULTS: Compared with controls, licofelone-treated rats had a grossly apparent decrease in inflammation and increased fibrocartilage formation at the enthesis, along with a 62% increase in the maximum load to failure and a 51% increase in peak stress to failure. Licofelone resulted in a marked reduction in fibrosis and lipid content in supraspinatus muscles as well as reduced expression of several genes involved in fatty infiltration. Despite the decline in fibrosis and fat accumulation, muscle fiber specific force production was reduced by 23%. CONCLUSION: The postoperative treatment of cuff repair with licofelone may reduce fatty degeneration and enhance the development of a stable bone-tendon interface, although decreases in muscle fiber specific force production were observed, and force production in fact declined. CLINICAL RELEVANCE: This study demonstrates that the inhibition of 5-LOX, COX-1, and COX-2 modulates the healing process of repaired rotator cuff tendons. Although further studies are necessary, the treatment of patients with licofelone after cuff repair may improve the development of a stable enthesis and enhance postoperative outcomes.

Elevation in circulating biomarkers of cartilage damage and inflammation in athletes with femoroacetabular impingement.

BACKGROUND: Femoroacetabular impingement (FAI) is one of the most common causes of early cartilage and labral damage in the nondysplastic hip. Biomarkers of cartilage degradation and inflammation are associated with osteoarthritis. It was not known whether patients with FAI have elevated levels of biomarkers of cartilage degradation and inflammation. HYPOTHESIS: Compared with athletes without FAI, athletes with FAI would have elevated levels of the inflammatory C-reactive protein (CRP) and cartilage oligomeric matrix protein (COMP), a cartilage degradation marker. STUDY DESIGN: Controlled laboratory study. METHODS: Male athletes with radiographically confirmed FAI (n = 10) were compared with male athletes with radiographically normal hips with no evidence of FAI or hip dysplasia (n = 19). Plasma levels of COMP and CRP were measured, and subjects also completed the Short Form-12 (SF-12) and Hip Disability and Osteoarthritis Outcome Score (HOOS) surveys. RESULTS: Compared with controls, athletes with FAI had a 24% increase in COMP levels and a 276% increase in CRP levels as well as a 22% decrease in SF-12 physical component scores and decreases in all of the HOOS subscale scores. CONCLUSION: Athletes with FAI demonstrate early biochemical signs of increased cartilage turnover and systemic inflammation. CLINICAL RELEVANCE: Chondral injury secondary to the repetitive microtrauma of FAI might be reliably detected with biomarkers. In the future, these biomarkers might be used as screening tools to identify at-risk patients and assess the efficacy of therapeutic interventions such as hip preservation surgery in altering the natural history and progression to osteoarthritis.

Changes in circulating biomarkers of muscle atrophy, inflammation, and cartilage turnover in patients undergoing anterior cruciate ligament reconstruction and rehabilitation.

BACKGROUND: After anterior cruciate ligament (ACL) reconstruction, there is significant atrophy of the quadriceps muscles that can limit full recovery and place athletes at risk for recurrent injuries with return to play. The cause of this muscle atrophy is not fully understood. HYPOTHESIS: Circulating levels of proatrophy, proinflammatory, and cartilage turnover cytokines and biomarkers would increase after ACL reconstruction. STUDY DESIGN: Descriptive laboratory study. METHODS: Patients (N = 18; mean age, 28 ± 2.4 years) underwent surgical reconstruction of the ACL after a noncontact athletic injury. Circulating levels of biomarkers were measured along with Short Form-12, International Knee Documentation Committee, and objective knee strength measures preoperatively and at 6 postoperative visits. Differences were tested using repeated-measures 1-way analysis of variance. RESULTS: Myostatin, TGF-ß, and C-reactive protein levels were significantly increased in the early postoperative period and returned to baseline. Cartilage oligomeric matrix protein levels decreased immediately after surgery and then returned to baseline. CCL2, CCL3, CCL4, CCL5, EGF, FGF-2, IGF-1, IL-10, IL-1α, IL-1ß, IL-1ra, IL-6, myoglobin, and TNF-α were not different over the course of the study. CONCLUSION: An increase in potent atrophy-inducing cytokines and corresponding changes in knee strength and functional scores were observed after ACL reconstruction. CLINICAL RELEVANCE: Although further studies are necessary, the therapeutic inhibition of myostatin may help prevent the muscle atrophy that occurs after ACL reconstruction and provide an accelerated return of patients to sport.

MMP inhibition as a potential method to augment the healing of skeletal muscle and tendon extracellular matrix.

The extracellular matrix (ECM) of skeletal muscle and tendon is composed of different types of collagen molecules that play important roles in the transmission of forces throughout the body, and in the repair and regeneration of injured tissues. Fibroblasts are the primary cells in muscle and tendon that maintain, repair, and modify the ECM in response to mechanical loading, injury, and inactivity. Matrix metalloproteinases (MMPs) are enzymes that digest collagen and other structural molecules, which are synthesized and excreted by fibroblasts. MMPs are required for baseline ECM homeostasis, but disruption of MMP regulation due to injury or disease can alter the normal ECM architecture and prevent proper force transmission. Chronic injuries and diseases of muscles and tendons can be severely debilitating, and current therapeutic modalities to enhance healing are quite limited. This review will discuss the mechanobiology of MMPs, and the potential use of MMP inhibitors to improve the treatment of injured and diseased skeletal muscle and tendon tissue.

Rotator cuff tear reduces muscle fiber specific force production and induces macrophage accumulation and autophagy.

Full-thickness tears to the rotator cuff can cause severe pain and disability. Untreated tears progress in size and are associated with muscle atrophy and an infiltration of fat to the area, a condition known as "fatty degeneration." To improve the treatment of rotator cuff tears, a greater understanding of the changes in the contractile properties of muscle fibers and the molecular regulation of fatty degeneration is essential. Using a rat model of rotator cuff injury, we measured the force generating capacity of individual muscle fibers and determined changes in muscle fiber type distribution that develop after a full thickness rotator cuff tear. We also measured the expression of mRNA and miRNA transcripts involved in muscle atrophy, lipid accumulation, and matrix synthesis. We hypothesized that a decrease in specific force of rotator cuff muscle fibers, an accumulation of type IIb fibers, and an upregulation in fibrogenic, adipogenic, and inflammatory gene expression occur in torn rotator cuff muscles. Thirty days following rotator cuff tear, we observed a reduction in muscle fiber force production, an induction of fibrogenic, adipogenic, and autophagocytic mRNA and miRNA molecules, and a dramatic accumulation of macrophages in areas of fat accumulation.