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Muscle degeneration is a common issue caused by rotator cuff tear (RCT) which significantly affects prognosis. Muscle stem cells (MuSCs) play a crucial role to prevent muscle degeneration after RCT. However, the pathological changes and detailed molecular mechanism underlying the myogenesis of MuSCs after RCT remain incomplete. The current study established single-cell landscape of supraspinatus muscles and found decreased expression of PIEZO1 and impaired myogenic potential of MuSCs from RCT patients. Reduced expression of PIEZO1 impaired the myogenesis of MuSCs by inhibiting the ERK/MAPK pathways. Furthermore, selective PIEZO1 agonist Yoda1 had the potential to alleviate muscle degeneration and improve shoulder function following RCT. This study emphasized the role of PIEZO1 in the myogenesis of MuSCs and suggested that activating PIEZO1 could be a potential non-surgical treatment option to reduce muscle degeneration after RCT.

Fatty infiltration of the rotator cuff muscles is very common following rotator cuff tears and is one of the most important factors in determining treatment. Current clinical practice relies on subjective evaluation of fatty infiltration through categorical scoring based on the Goutallier classification system. The Dixon magnetic resonance imaging (MRI) sequence provides flexibility in selecting echo times for water–fat separation. The Dixon method, therefore, has the potential to provide robust and high-quality fat quantification that allows for more accurate calculation of fat fraction (%Fat) of the rotator cuff muscles than the Goutallier classification system. However, significant variance exists in sequencing and post-processing methodology within the recent application of Dixon sequences to quantify rotator cuff fatty infiltration. In this paper, we conducted a systematic review to synthesize the relevant literature utilizing Dixon sequencing for the quantification of rotator cuff fatty infiltration. The literature search was extracted from 1094 articles, with 12 studies included in the final review. Regardless of the varying sequencing pattern and post-processing techniques among studies, the findings suggest the Dixon method is reliable for quantitatively calculating the fat fraction of the rotator cuff muscles, even at very low levels of fatty infiltration. In addition, a quantitative difference in fat fraction was observed between participants with different degrees of tear vs. those without any shoulder pathologies. Multi-point Dixon imaging has the potential to be utilized clinically to objectively quantify fatty infiltration and may lead to improved clinical decision making for patients with rotator cuff tears.

PURPOSE: The purpose of this study was to understand potential baseline transcriptional expression differences in paraspinal skeletal muscle from patients with different underlying lumbar pathologies by comparing multifidus gene expression profiles across individuals with either disc herniation, facet arthropathy, or degenerative spondylolisthesis. METHODS: Multifidus biopsies were obtained from patients (n = 44) undergoing lumbar surgery for either disc herniation, facet arthropathy, or degenerative spondylolisthesis. Diagnostic categories were based on magnetic resonance images, radiology reports, and intraoperative reports. Gene expression for 42 genes was analysed using qPCR. A one-way analysis of variance was performed for each gene to determine differences in expression across diagnostic groups. Corrections for multiple comparisons across genes (Benjamini-Hochberg) and for between-group post hoc comparisons (Sidak) were applied. RESULTS: Adipogenic gene (ADIPOQ) expression was higher in the disc herniation group when compared to the facet arthropathy group (p = 0.032). Adipogenic gene (PPARD) expression was higher in the degenerative spondylolisthesis group when compared to the disc herniation group (p = 0.013), although absolute gene expression levels for all groups was low. Fibrogenic gene (COL3A1) had significantly higher expression in the disc herniation group and facet arthropathy group when compared to the degenerative spondylolisthesis group (p

A common animal model of muscle pathology following rotator cuff tear (RCT) is a tenotomy of the supraspinatus and infraspinatus, often combined with neurotomy of the suprascapular nerve, which induces a more robust atrophy response than tenotomy alone. However, the utility of this model depends on its similarity to human muscle pathology post‐RCT, both in terms of the disease phenotype and mechanisms of muscle atrophy and fatty infiltration. Given the clinical prevalence of nerve injury is low and the muscular response to denervation is distinct from mechanical unloading in other models, an understanding of the biological influence of the nerve injury is critical for interpreting data from this RCT model. We evaluated the individual and combined effect of tenotomy and neurotomy across multiple biological scales, in a robust time‐series in the mouse supraspinatus. Muscle composition, histological, and gene expression data related to muscle atrophy, degeneration–regeneration, fatty infiltration, and fibrosis were evaluated. Broadly, we found tenotomy alone caused small, transient changes in these pathological features, which resolved over the course of the study, while neurotomy alone caused a significant fatty atrophy phenotype. The dual injury group had a similar fatty atrophy phenotype to the neurotomy group, though the addition of tenotomy did marginally enhance the fat and connective tissue. Overall, these results suggest the most clinically relevant injury model, tenotomy alone, does not produce a clinically relevant phenotype. The dual injury model partially recapitulates the human condition, but it does so through a nerve injury, which is not well justified clinically. [ABSTRACT FROM AUTHOR]

Background: Patients treated for symptomatic rotator cuff tear (RCT) on one shoulder seem to have a higher prevalence of RCT on the contralateral shoulder. Purpose: To compare the supraspinatus (SSP) tendon and RC muscle properties on the contralateral shoulder in patients after repair surgery to those healthy individuals using quantitative magnetic resonance imaging (MRI). Material and Methods: A total of 23 patients treated for RCT (group A) and 23 healthy controls (group B) were recruited. Constant score, visual analog scale score (VAS), and MRI examinations were conducted. The SSP tendon structural status was graded based on the Zlatkin classification and quantified on ultrashort echo time (UTE)-T2* mapping images. Fatty degeneration of RC muscles was classified according to the Goutallier classification and quantified on T2 mapping. Results: The Constant and VAS scores were comparable between groups A and B (all P >0.05). No significant differences were observed in tendon structural status between the two groups (P >0.05). However, significant differences were established in UTE-T2* values of the SSP tendon on the distal subregion between groups A and B (16.4 ± 2.4 ms vs. 14.8 ± 1.2 ms; P = 0.01). Regarding muscle degeneration, no significant differences were displayed in T2 values and Goutallier classification of RC muscles (all P >0.05). Conclusion: Patients with a treated RCT demonstrated inferior SSP tendon in the distal subregion on the contralateral shoulders one year postoperatively compared to that of healthy controls based on quantitative MRI data. [ABSTRACT FROM AUTHOR]

Fatty infiltration of the rotator cuff muscles is very common following rotator cuff tears and is one of the most important factors in determining treatment. Current clinical practice relies on subjective evaluation of fatty infiltration through categorical scoring based on the Goutallier classification system. The Dixon magnetic resonance imaging (MRI) sequence provides flexibility in selecting echo times for water–fat separation. The Dixon method, therefore, has the potential to provide robust and high-quality fat quantification that allows for more accurate calculation of fat fraction (%Fat) of the rotator cuff muscles than the Goutallier classification system. However, significant variance exists in sequencing and post-processing methodology within the recent application of Dixon sequences to quantify rotator cuff fatty infiltration. In this paper, we conducted a systematic review to synthesize the relevant literature utilizing Dixon sequencing for the quantification of rotator cuff fatty infiltration. The literature search was extracted from 1094 articles, with 12 studies included in the final review. Regardless of the varying sequencing pattern and post-processing techniques among studies, the findings suggest the Dixon method is reliable for quantitatively calculating the fat fraction of the rotator cuff muscles, even at very low levels of fatty infiltration. In addition, a quantitative difference in fat fraction was observed between participants with different degrees of tear vs. those without any shoulder pathologies. Multi-point Dixon imaging has the potential to be utilized clinically to objectively quantify fatty infiltration and may lead to improved clinical decision making for patients with rotator cuff tears. [ABSTRACT FROM AUTHOR]

Aims: Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells. Methods: HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential. Results: Vorinostat, a HDACi compound, blocked the adipogenic transformation of muscle-associated FAPs in culture, promoting myogenic progression of the satellite cells. Furthermore, it protected muscle from degeneration after acute RC in mice in the earlier muscle degenerative stage after tenotomy. Conclusion: The HDACi vorinostat may be a candidate to prevent early muscular degeneration after RC injury. Cite this article: Bone Joint Res 2024;13(4):169–183.

Background: Muscle edema formation and inflammatory processes are early manifestations of acute rotator cuff lesions in sheep. Histological analysis of affected muscles revealed edema formation, inflammatory changes, and muscle tissue disruption in MRs. Hypothesis: Edema contributes to inflammatory reactions and early muscle fiber degeneration before the onset of fatty infiltration. Study Design: Controlled laboratory study. Methods: Osteotomy of the greater tuberosity, including the insertion of the infraspinatus tendon, was performed on 14 sheep. These experimental animal models were divided into 2 groups: a nontrauma group with surgical muscle release alone (7 sheep) and a trauma group with standardized application of additional trauma to the musculotendinous unit (7 sheep). Excisional biopsy specimens of the infraspinatus muscle were taken at 0, 3, and 4 weeks. Results: Edema formation was histologically demonstrated in both groups and peaked at 3 weeks. At 3 weeks, signs of muscle fiber degeneration were observed. At 4 weeks, ingrowth of loose alveolar and fibrotic tissue between fibers was detected. Fatty tissue was absent. The diameter of muscle fibers increased in both groups, albeit to a lesser degree in the trauma group, and practically normalized at 4 weeks. Immunohistology revealed an increase in macrophage types 1 and 2, as well as inflammatory mediators such as prostaglandin E2 and nuclear factor kappa-light-chain-enhancer of activated B cells. Conclusion: Early muscle edema and concomitant inflammation precede muscle fiber degeneration and fibrosis. Edema formation results from tendon release alone and is only slightly intensified by additional trauma. Clinical Relevance: This study illustrates that early edema formation and inflammation elicit muscle fiber degeneration that precedes fatty infiltration. Should this phenomenon be applicable to human traumatic rotator cuff tears, then surgery should be performed as soon as possible, ideally within the first 21 days after injury. [ABSTRACT FROM AUTHOR]

Aims: Rotator cuff muscle atrophy and fatty infiltration affect the clinical outcomes of rotator cuff tear patients. However, there is no effective treatment for fatty infiltration at this time. High-intensity interval training (HIIT) helps to activate beige adipose tissue. The goal of this study was to test the role of HIIT in improving muscle quality in a rotator cuff tear model via the β3 adrenergic receptor (β3AR). Methods: Three-month-old C57BL/6 J mice underwent a unilateral rotator cuff injury procedure. Mice were forced to run on a treadmill with the HIIT programme during the first to sixth weeks or seventh to 12th weeks after tendon tear surgery. To study the role of β3AR, SR59230A, a selective β3AR antagonist, was administered to mice ten minutes before each exercise through intraperitoneal injection. Supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat were harvested at the end of the 12th week after tendon tear and analyzed biomechanically, histologically, and biochemically. Results: Histological analysis of supraspinatus muscle showed that HIIT improved muscle atrophy, fatty infiltration, and contractile force compared to the no exercise group. In the HIIT groups, supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat showed increased expression of tyrosine hydroxylase and uncoupling protein 1, and upregulated the β3AR thermogenesis pathway. However, the effect of HIIT was not present in mice injected with SR59230A, suggesting that HIIT affected muscles via β3AR. Conclusion: HIIT improved supraspinatus muscle quality and function after rotator cuff tears by activating systemic sympathetic nerve fibre near adipocytes and β3AR. Cite this article: Bone Joint Res 2023;12(8):455–466.

Peripheral arterial disease (PAD) leads to chronic vascular occlusion and results in end organ damage in critically perfused limbs. There are currently no clinical methods available to determine the muscular damage induced by chronic mal-perfusion. This monocentric prospective cross-sectional study investigated n = 193 adults, healthy to severe PAD, in order to quantify the degree of calf muscle degeneration caused by PAD using a non-invasive hybrid ultrasound and single wavelength optoacoustic imaging (US/SWL-OAI) approach. While US provides morphologic information, SWL-OAI visualizes the absorption of pulsed laser light and the resulting sound waves from molecules undergoing thermoelastic expansion. US/SWL-OAI was compared to multispectral data, clinical disease severity, angiographic findings, phantom experiments, and histological examinations from calf muscle biopsies. We were able to show that synergistic use of US/SWL-OAI is most likely to map clinical degeneration of the muscle and progressive PAD.

Fatty expansion is one of the features of muscle degeneration due to muscle injuries, and its presence interferes with muscle regeneration. Specifically, poor clinical outcomes have been linked to fatty expansion in rotator cuff tears and repairs. Our group recently found that fibroblast growth factor 8b (FGF-8b) inhibits adipogenic differentiation and promotes myofiber formation of mesenchymal stem cells in vitro. This led us to hypothesize that FGF-8b could similarly control the fate of muscle-specific cell populations derived from rotator cuff muscle involved in muscle repair following rotator cuff injury. In this study, we isolate fibro-adipogenic progenitor cells (FAPs) and satellite stem cells (SCs) from rat rotator cuff muscle tissue and analyzed the effects of FGF-8b supplementation. Utilizing a cell plating protocol, we successfully isolate FAPs-rich fibroblasts (FIBs) and SCs-rich muscle progenitor cells (MPCs). Subsequently, we demonstrate that FIB adipogenic differentiation can be inhibited by FGF-8b, while MPC myogenic differentiation can be enhanced by FGF-8b. We further demonstrate that phosphorylated ERK due to FGF-8b leads to the inhibition of adipogenesis in FIBs and SCs maintenance and myofiber formation in MPCs. Together, these findings demonstrate the powerful potential of FGF-8b for rotator cuff repair by altering the fate of muscle undergoing degeneration. [ABSTRACT FROM AUTHOR]

The aim was to study the evolution and severity of white striping and wooden breast myopathies and to carry out a study on the parameters of meat quality and allometric growth of male and female broilers at different ages. The experiment was conducted in a broiler house in a completely randomized design, using 960 one-day-old chicks of the Cobb® strain, with 480 chicks of each sex. 96 birds per treatment were slaughtered weekly at the age of 21 to 49 days. The present study analyses the occurrence of myopathies, their scores, and their evolution over the age of the birds, comparing males and females. Further assessments included the allometric coefficient and meat quality analyses such as physical measurements (breast length, width, and thickness), pH, colour (L*, a*, and b*), drip loss, water-holding capacity, cooking loss, and shear force. The results demonstrate that the sex of birds did not affect the occurrence of white striping and wooden breast myopathies. However, the degree of myopathies evolved with advancing age, suggesting the weight as a predisposing factor for these myopathies. The emergence of white striping myopathy occurred as early as in the third week of the birds' life. Wooden breast did not develop as isolated myopathy, occurring only in the concomitant presence of white striping. The allometric coefficient demonstrated that regardless of the sex and age, broiler breast had positive heterogonic growth, i.e. late growth in relation to the other parts of the body.

Rotator cuff tears are a prevalent musculoskeletal problem that affect many individuals and may result in substantial social and health-related expenses. Moreover, the muscular fat infiltration and dystrophy associated with rotator cuff tears have been persistent challenges in rotator cuff surgical repair and postoperative rehabilitation. In this study, an in situ-formed injectable sodium alginate (SA) and bioglass (BG) hydrogel consisting of poly (lactic-co-glycolic acid) (PLGA) microspheres containing metformin (SA/BG-PLGA-Met) was developed for the prevention of muscular fat infiltration and dystrophy. Metformin and silicon ions were slowly released by the combined hydrogel, resulting in long-term biological effects. Moreover, the hydrogel displayed excellent degradability and biocompatibility. Extracts of SA/BG-PLGA-Met inhibited the adipogenesis of 3T3-L1 cells and stimulated the myogenic differentiation of C2C12 cells in vitro. In a mouse model of rotator cuff degeneration, the SA/BG-PLGA-Met hydrogel inhibited fat infiltration and dystrophy of the supraspinatus muscle. Overall, the SA/BG-PLGA-Met hydrogel, as a novel biomaterial, has great clinical potential for preventing rotator cuff muscle fat infiltration and atrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant epigenetic disorder with highly variable muscle involvement and disease progression. Ongoing clinical trials, aimed at counteracting muscle degeneration and disease progression in FSHD patients, increase the need for reliable biomarkers. Muscle magnetic resonance imaging (MRI) studies showed that the appearance of STIR-positive (STIR+) lesions in FSHD muscles represents an initial stage of muscle damage, preceding irreversible adipose changes. Our study aimed to investigate fibrosis, a parameter of muscle degeneration undetectable by MRI, in relation to disease activity and progression of FSHD muscles. We histologically evaluated collagen in FSHD1 patients’ (STIR+ n = 27, STIR− n = 28) and healthy volunteers’ (n = 12) muscles by picrosirius red staining. All patients (n = 55) performed muscle MRI before biopsy, 45 patients also after 1 year and 36 patients also after 2 years. Fat content (T1 signal) and oedema/inflammation (STIR signal) were evaluated at baseline and at 1- and 2-year MRI follow-up. STIR+ muscles showed significantly higher collagen compared to both STIR− (p = 0.001) and healthy muscles (p < 0.0001). STIR− muscles showed a higher collagen content compared to healthy muscles (p = 0.0194). FSHD muscles with a worsening in fatty infiltration during 1- (P = 0.007) and 2-year (P < 0.0001) MRI follow-up showed a collagen content of 3.6- and 3.7-fold higher compared to FSHD muscles with no sign of progression. Moreover, the fibrosis was significantly higher in STIR+ muscles who showed a worsening in fatty infiltration in a timeframe of 2 years compared to both STIR− (P = 0.0006) and STIR+ muscles with no sign of progression (P = 0.02). Fibrosis is a sign of muscle degeneration undetectable at MRI never deeply investigated in FSHD patients. Our data show that 23/27 of STIR+ and 12/28 STIR− muscles have a higher amount of collagen deposition compared to healthy muscles. Fibrosis is higher in FSHD muscles with a worsening in fatty infiltration thus suggesting that its evaluation with innovative non-invasive techniques could be a candidate prognostic biomarker for FSHD, to be used to stratify patients and to evaluate the efficacy of therapeutic treatments. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency, prevalent worldwide, is linked to muscle weakness, sarcopenia, and falls. Muscle regeneration is a vital process that allows for skeletal muscle tissue maintenance and repair after injury. PubMed and Web of Science were used to search for studies published prior to May 2023. We assessed eligible studies that discussed the relationship between vitamin D, muscle regeneration in this review. Overall, the literature reports strong associations between vitamin D and skeletal myocyte size, and muscle regeneration. In vitro studies in skeletal muscle cells derived from mice and humans showed vitamin D played a role in regulating myoblast growth, size, and gene expression. Animal studies, primarily in mice, demonstrate vitamin D's positive effects on skeletal muscle function, such as improved grip strength and endurance. These studies encompass vitamin D diet research, genetically modified models, and disease-related mouse models. Relatively few studies looked at muscle function after injury, but these also support a role for vitamin D in muscle recovery. The human studies have also reported that vitamin D deficiency decreases muscle grip strength and gait speed, especially in the elderly population. Finally, human studies reported the benefits of vitamin D supplementation and achieving optimal serum vitamin D levels in muscle recovery after eccentric exercise and surgery. However, there were no benefits in rotator cuff injury studies, suggesting that repair mechanisms for muscle/ligament tears may be less reliant on vitamin D. In summary, vitamin D plays a crucial role in skeletal muscle function, structural integrity, and regeneration, potentially offering therapeutic benefits to patients with musculoskeletal diseases and in post-operative recovery. [ABSTRACT FROM AUTHOR]

Abstract Background We examined the association between levothyroxine use and longitudinal MRI biomarkers for thigh muscle mass and composition in at-risk participants for knee osteoarthritis (KOA) and their mediatory role in subsequent KOA incidence. Methods Using the Osteoarthritis Initiative (OAI) data, we included the thighs and corresponding knees of participants at risk but without established radiographic KOA (baseline Kellgren-Lawrence grade (KL) < 2). Levothyroxine users were defined as self-reported use at all annual follow-up visits until the 4th year and were matched with levothyroxine non-users for potential confounders (KOA risk factors, comorbidities, and relevant medications covariates) using 1:2/3 propensity score (PS) matching. Using a previously developed and validated deep learning method for thigh segmentation, we assessed the association between levothyroxine use and 4-year longitudinal changes in muscle mass, including cross-sectional area (CSA) and muscle composition biomarkers including intra-MAT (within-muscle fat), contractile percentage (non-fat muscle CSA/total muscle CSA), and specific force (force per CSA). We further assessed whether levothyroxine use is associated with an 8-year risk of standard KOA radiographic (KL ≥ 2) and symptomatic incidence (incidence of radiographic KOA and pain on most of the days in the past 12 months). Finally, using a mediation analysis, we assessed whether the association between levothyroxine use and KOA incidence is mediated via muscle changes. Results We included 1043 matched thighs/knees (266:777 levothyroxine users:non-users; average ± SD age: 61 ± 9 years, female/male: 4). Levothyroxine use was associated with decreased quadriceps CSAs (mean difference, 95%CI: − 16.06 mm2/year, − 26.70 to − 5.41) but not thigh muscles’ composition (e.g., intra-MAT). Levothyroxine use was also associated with an increased 8-year risk of radiographic (hazard ratio (HR), 95%CI: 1.78, 1.15–2.75) and symptomatic KOA incidence (HR, 95%CI: 1.93, 1.19–3.13). Mediation analysis showed that a decrease in quadriceps mass (i.e., CSA) partially mediated the increased risk of KOA incidence associated with levothyroxine use. Conclusions Our exploratory analyses suggest that levothyroxine use may be associated with loss of quadriceps muscle mass, which may also partially mediate the increased risk of subsequent KOA incidence. Study interpretation should consider underlying thyroid function as a potential confounder or effect modifier. Therefore, future studies are warranted to investigate the underlying thyroid function biomarkers for longitudinal changes in the thigh muscles.

Skeletal muscle is one of the leading frameworks of the musculo-skeletal system, which works in synergy with the bones. Long skeletal muscles provide stability and mobility to the human body and are primarily composed of proteins. Conversely, improper functioning of various skeletal muscles leads to diseases and disorders, namely, age-related muscle disorder called sarcopenia, a group of genetic muscle disorders such as muscular dystrophies, and severe muscle wasting in cancer known as cachexia. However, skeletal muscle has an excellent ability to undergo hypertrophy and enhanced functioning during sustained exercise over time. Indeed, these processes of skeletal muscle regeneration/hypertrophy, as well as degeneration and atrophy, involve an interplay of various signaling pathways. Myostatin is one such chemokine/myokine with a significant contribution to muscle regeneration or atrophy in multiple conditions. In this review, we try to put together the role and regulation of myostatin as a function of muscle regeneration extrapolated to multiple aspects of its molecular functions.

Abstract Background Cathelicidin, an antimicrobial peptide, plays a key role in regulating bacterial killing and innate immunity; however, its role in skeletal muscle function is unknown. We investigated the potential role of cathelicidin in skeletal muscle pathology resulting from acute injury and Duchenne muscular dystrophy (DMD) in mice. Methods Expression changes and muscular localization of mouse cathelicidin‐related antimicrobial peptide (Cramp) were examined in the skeletal muscle of normal mice treated with chemicals (cardiotoxin and BaCl2) or in dystrophic muscle of DMD mouse models (mdx, mdx/Utrn+/− and mdx/Utrn−/−). Cramp penetration into myofibres and effects on muscle damage were studied by treating synthetic peptides to mouse skeletal muscles or C2C12 myotubes. Cramp knockout (KO) mice and mdx/Utrn/Cramp KO lines were used to determine whether Cramp mediates muscle degeneration. Muscle pathophysiology was assessed by histological methods, serum analysis, grip strength and lifespan. Molecular factors targeted by Cramp were identified by the pull‐down assay and proteomic analysis. Results In response to acute muscle injury, Cramp was activated in muscle‐infiltrating neutrophils and internalized into myofibres. Cramp treatments of mouse skeletal muscles or C2C12 myotubes resulted in muscle degeneration and myotube damage, respectively. Genetic ablation of Cramp reduced neutrophil infiltration and ameliorated muscle pathology, such as fibre size (P

Purpose: We investigated loco-regional degenerative changes' association with incidentally found non-traumatic vertebral body fractures of the lower thoracic and lumbar spine in older patients. Methods: The patient collective included patients in the age range of 50 to 90 years. Vertebral bodies from T7 to L5 were included. Vertebral body fractures were classified according to Genant. The following loco-regional osseous and extra-osseous degenerative changes were included: osteochondrosis, spondylarthritis, facet joint asymmetries, spondylolisthesis, scoliosis as well as fatty degeneration and asymmetry of the autochthonous back muscles. Patients with traumatic and tumor-related vertebral body fractures were excluded. Non-traumatic fractures of the lower thoracic and lumbar spine were evaluated separately. The Mann–Whitney U-test was used, and relative risks (RRs) were calculated for statistics. Pearson's correlations (Rs) were used to correlate grades of degenerative changes and fracture severities. Results: 105 patients were included. Fatty deposits in the autochthonous muscles of the lower thoracic and the lumbar spine were associated with non-traumatic vertebral body fractures in the lower thoracic spine (p = 0.005, RR = 4.92). In contrast, muscle fatness of the autochthonous muscles was not a risk factor for lumbar spine fractures (p = 0.157, RR = 2.04). Additionally, we found a moderate correlation between fatty degeneration of the autochthonous muscles and the severity of fractures in the lower thoracic spine (RR = 0.34, p < 0.001). The other degenerative changes did not present any significant difference or correlation between the evaluated groups. Conclusions: Fatty degeneration of the autochthonous spinal musculature is associated with incidentally found non-traumatic fractures of the lower thoracic spine. [ABSTRACT FROM AUTHOR]

The aim was to study the evolution and severity of white striping and wooden breast myopathies and to carry out a study on the parameters of meat quality and allometric growth of male and female broilers at different ages. The experiment was conducted in a broiler house in a completely randomized design, using 960 one-day-old chicks of the Cobb® strain, with 480 chicks of each sex. 96 birds per treatment were slaughtered weekly at the age of 21 to 49 days. The present study analyses the occurrence of myopathies, their scores, and their evolution over the age of the birds, comparing males and females. Further assessments included the allometric coefficient and meat quality analyses such as physical measurements (breast length, width, and thickness), pH, colour (L*, a*, and b*), drip loss, water-holding capacity, cooking loss, and shear force. The results demonstrate that the sex of birds did not affect the occurrence of white striping and wooden breast myopathies. However, the degree of myopathies evolved with advancing age, suggesting the weight as a predisposing factor for these myopathies. The emergence of white striping myopathy occurred as early as in the third week of the birds' life. Wooden breast did not develop as isolated myopathy, occurring only in the concomitant presence of white striping. The allometric coefficient demonstrated that regardless of the sex and age, broiler breast had positive heterogonic growth, i.e. late growth in relation to the other parts of the body. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a disease of joint degeneration and impaired function. Muscle atrophy, fatty infiltration, and fibrosis are degenerative features of muscle injury and predict poor outcomes in some degenerative and exercise-related injuries. Patients with glenohumeral joint OA usually have rotator cuff muscle degeneration, even though the rotator cuff is intact. However, the mechanism and correlation between OA and degeneration of muscles around joints are still unknown. Forty-five 12-month-old C57BL/6J mice received a single injection of monoiodoacetic acid into the right glenohumeral joint. The sham group was injected with saline on the same day in the right glenohumeral joint. Three and 6 weeks after the operation, gait analysis was conducted to evaluate the function of the forelimb. Then, the shoulder joint and supraspinatus muscle were collected for histologic staining, reverse transcription quantitative polymerase chain reaction, and biomechanics test. Correlations between fat area fraction in muscle, percentage wet muscle weight change or Osteoarthritis Research Society International score, and gait analysis/muscle mechanics tests were assessed using Pearson's correlation coefficient or Spearman's correlation coefficient. Compared with the sham group, the monoiodoacetic acid group developed significant glenohumeral joint OA and the supraspinatus muscle developed significant fatty infiltration and muscle atrophy. Shoulder function correlated with glenohumeral joint OA/rotator cuff muscle severity, weight loss, and fatty infiltration. In mice, glenohumeral joint OA can lead to rotator cuff degeneration and inferior limb function. The small animal model could be a powerful tool to further study the potential mechanisms between glenohumeral OA and rotator cuff muscle degeneration. [ABSTRACT FROM AUTHOR]

Skeletal muscle is the most abundant tissue in the body and requires high levels of energy to function properly. Skeletal muscle allows voluntary movement and body posture, which require different types of fiber, innervation, energy, and metabolism. Here, we summarize the contribution received at the time of publication of this Introductory Issue for the Special Issue dedicated to "Skeletal Muscle Atrophy: Mechanisms at a Cellular Level". The Special Issue is divided into three sections. The first is dedicated to skeletal muscle pathophysiology, the second to disease mechanisms, and the third to therapeutic development. [ABSTRACT FROM AUTHOR]

Abstract Background To compare changes in the composition of paraspinal muscles of patients with ankylosing spondylitis (AS) and matched healthy controls using T2 mapping and T2 IDEAL and correlate the quantitative magnetic resonance imaging (qMRI) results with clinical assessments of AS patients. Method In total, 37 AS patients and 37 healthy controls were enrolled in the case control study. T2 mapping with and without fat saturation and IDEAL imaging were used to assess the multifidus (MF) and erector spinae (ES) at the levels of L3/L4 and L4/L5 for all subjects. Mean T2non-fatsat, T2fat, T2fatsat, cross-sectional area (CSA), and fat fraction (FF) were compared between AS and healthy controls. Correlations of qMRI results with clinical assessments were analyzed in AS. Results Significantly elevated mean T2non-fatsat values and the FF of the MF and ES at both levels were observed in AS and compared to the controls (p 0.05). Conclusions Our findings indicate that using a combination of IDEAL and T2 mapping may provide deeper insights into the pathophysiological degeneration of paraspinal muscles in AS.

Abstract Background Degeneration of shoulder muscle tissues often result in tearing, causing pain, disability and loss of independence. Differential muscle involvement patterns have been reported in tears of shoulder muscles, yet the molecules involved in this pathology are poorly understood. The spatial distribution of biomolecules across the affected tissue can be accurately obtained with matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI). The goal of this pilot study was to decipher the metabolic landscape across shoulder muscle tissues and to identify signatures of degenerated muscles in chronic conditions. Methods Paired biopsies of two rotator cuff muscles, torn infraspinatus and intact teres minor, together with an intact shoulder muscle, the deltoid, were collected during an open tendon transfer surgery. Five patients, average age 65.2 ± 3.8 years, were selected for spatial metabolic profiling using high‐spatial resolution (MALDI‐TOF) and high‐mass resolution (MALDI‐FTICR) MSI in negative or positive ion mode. Metabolic signatures were identified using data‐driven analysis. Verifications of spatial localization for selected metabolic signatures were carried out using antibody immunohistology. Results Data‐driven analysis revealed major metabolic differences between intact and degenerated regions across all muscles. The area of degenerated regions, encompassed of fat, inflammation and fibrosis, significantly increased in both rotator cuff muscles, teres minor (27.9%) and infraspinatus (22.8%), compared with the deltoid (8.7%). The intact regions were characterized by 49 features, among which lipids were recognized. Several of the identified lipids were specifically enriched in certain myofiber types. Degenerated regions were specifically marked by the presence of 37 features. Heme was the most abundant metabolite in degenerated regions, whereas Heme oxygenase‐1 (HO‐1), which catabolizes heme, was found in intact regions. Higher HO‐1 levels correlated with lower heme accumulation. Conclusions Degenerated regions are distinguished from intact regions by their metabolome profile. A muscle‐specific metabolome profile was not identified. The area of tissue degeneration significantly differs between the three examined muscles. Higher HO‐1 levels in intact regions concurred with lower heme levels in degenerated regions. Moreover, HO‐1 levels discriminated between dysfunctional and functional rotator cuff muscles. Additionally, the enrichment of specific lipids in certain myofiber types suggests that lipid metabolism differs between myofiber types. The signature metabolites can open options to develop personalized treatments for chronic shoulder muscles degeneration.

Rotator cuff (RC) muscles undergo several detrimental changes following mechanical unloading resulting from RC tendon tear. In this review, we highlight the pathological causes and consequences of mechanical alterations at the whole muscle, muscle fiber, and muscle resident cell level as they relate to RC disease progression. In brief, the altered mechanical loads associated with RC tear lead to architectural, structural, and compositional changes at the whole-muscle and muscle fiber level. At the cellular level, these changes equate to direct disruption of mechanobiological signaling, which is exacerbated by mechanically regulated biophysical and biochemical changes to the cellular and extra-cellular environment (also known as the stem cell "niche"). Together, these data have important implications for both pre-clinical models and clinical practice. In pre-clinical models, it is important to recapitulate both the atrophic and degenerative muscle loss found in humans using clinically relevant modes of injury. Clinically, understanding the mechanics and underlying biology of the muscle will impact both surgical decision-making and rehabilitation protocols, as interventions that may be good for atrophic muscle will have a detrimental effect on degenerating muscle, and vice versa. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:546-556, 2018.

Muscular dystrophies (DM) are neurological conditions of great complexity and severity that involve progressive loss of muscle mass and associated reduction in muscle strength. The causes are genetic and involve mutations in the dystrophin gene that lead to the absence or deficiency of functional dystrophin, a cytoskeletal protein that enables general muscle function. In neuromuscular dystrophies there are direct molecular mechanisms responsible for exercise intolerance and inability to contract muscles. The use of therapeutic physical exercises is a way to slow down the preogression of the disease, to combat the loss of functionality of the muscle fibers as well as to delay the appearance of secondary manifestations of the disease, manifestations that occur with the ability to ambulate and with the installation of sedentarism caused by muscle weakness and degeneration. The effects of therapeutic exercise on patients with muscular dystrophy (including the effects of exceptional or maximal exercise) have been analyzed in the literature, and it has been found that aerobic exercise performed under the guidance of a physical therapist can be effective in improving oxidative capacity and progressive muscle function of the patient. The exercises must be adapted to the individual case, depending on the patient's general condition and availability of effort. Careful supervision and monitoring of patients can achieve the objectives obtained in the form of beneficial effects for the affected muscles. The present dissemination proposes a brief presentation of different types of therapeutic exercises (aerobic, endurance, resistance) and their role in the recovery program of patients with progressive muscular dystrophies. [ABSTRACT FROM AUTHOR]

Background and Objectives: The aim of this study was to evaluate the impact of sagittal imbalance based on pelvic incidence–lumbar lordosis (PI-LL) mismatch on the analgesic efficacy of epidural steroid injection in geriatric patients. Materials and Methods: Patients aged 65 years or older who received lumbar epidural steroid injections under fluoroscopy were enrolled. The cutoff of PI-LL mismatch >20° was used as an indicator of a marked sagittal imbalance. The cross-sectional area of the psoas and paraspinal muscles, as well as the paraspinal fat infiltration grade were measured. A 50% or more decrease in pain score at four weeks after injection was considered as good analgesia. Variables were compared between PI-LL ≤ 20° and >20° groups and multivariate analysis was used to identify factors related to pain relief after injection. Results: A total of 237 patients consisting of 150 and 87 patients in the PI-LL ≤ 20° and >20° groups, respectively, were finally analyzed. Female patients, patients with lumbar surgery history, and the smaller cross-sectional area of the psoas muscles were predominantly observed in patients with sagittal imbalance. There was no difference in analgesic outcome after injection according to the PI-LL mismatch (good analgesia 60.0 vs. 60.9%, p = 0.889). Multivariate analysis showed that pre-injection opioid use, moderate to severe foraminal stenosis, and high-graded paraspinal fat infiltration were significantly associated with poor analgesia after injection. Conclusions: There was no significant correlation between sagittal spinopelvic alignment and pain relief after lumbar epidural steroid injection for geriatric patients. [ABSTRACT FROM AUTHOR]

Massive rotator cuff tears (MRCTs) of the shoulder cause disability and pain among the adult population. In chronic injuries, the tendon retraction and subsequently the loss of mechanical load lead to muscle atrophy, fat accumulation, and fibrosis formation over time. The intrinsic repair mechanism of muscle and the successful repair of the torn tendon cannot reverse the muscle degeneration following MRCTs. To address these limitations, we developed an electroconductive matrix by incorporating graphene nanoplatelets (GnPs) into aligned poly(l-lactic acid) (PLLA) nanofibers. This study aimed to understand 1) the effects of GnP matrices on muscle regeneration and inhibition of fat formation in vitro and 2) the ability of GnP matrices to reverse muscle degenerative changes in vivo following an MRCT. The GnP matrix significantly increased myotube formation, which can be attributed to enhanced intracellular calcium ions in myoblasts. Moreover, the GnP matrix suppressed adipogenesis in adipose-derived stem cells. These results supported the clinical effects of the GnP matrix on reducing fat accumulation and muscle atrophy. The histological evaluation showed the potential of the GnP matrix to reverse muscle atrophy, fat accumulation, and fibrosis in both supraspinatus and infraspinatus muscles at 24 and 32 wk after the chronic MRCTs of the rat shoulder. The pathological evaluation of internal organs confirmed the long-term biocompatibility of the GnP matrix. We found that reversing muscle degenerative changes improved the morphology and tensile properties of the tendon compared with current surgical techniques. The long-term biocompatibility and the ability of the GnP matrix to treat muscle degeneration are promising for the realization of MRCT healing and regeneration. [ABSTRACT FROM AUTHOR]

Background: To compare changes in the composition of paraspinal muscles of patients with ankylosing spondylitis (AS) and matched healthy controls using T2 mapping and T2 IDEAL and correlate the quantitative magnetic resonance imaging (qMRI) results with clinical assessments of AS patients.Method: In total, 37 AS patients and 37 healthy controls were enrolled in the case control study. T2 mapping with and without fat saturation and IDEAL imaging were used to assess the multifidus (MF) and erector spinae (ES) at the levels of L3/L4 and L4/L5 for all subjects. Mean T2non-fatsat, T2fat, T2fatsat, cross-sectional area (CSA), and fat fraction (FF) were compared between AS and healthy controls. Correlations of qMRI results with clinical assessments were analyzed in AS.Results: Significantly elevated mean T2non-fatsat values and the FF of the MF and ES at both levels were observed in AS and compared to the controls (p < 0.05). The mean T2fatsat values of ES and MF were significantly higher only at the level of L3/L4 in AS compared to healthy controls (p < 0.05). A loss of muscle CSA compatible with atrophy was present in MF and ES at both levels in AS compared to the controls (p < 0.05). Weak to moderate positive correlations were found between FF and age and disease duration in AS (r = 0.318-0.415, p < 0.05). However, such positive correlation was not observed between FF and disease duration after adjusting for age (p > 0.05).Conclusions: Our findings indicate that using a combination of IDEAL and T2 mapping may provide deeper insights into the pathophysiological degeneration of paraspinal muscles in AS. [ABSTRACT FROM AUTHOR]

Abstract Background Muscle strength around the hip after total hip arthroplasty (THA) is crucial for preventing dislocation and limping. This study aimed to assess and compare muscle volume and degeneration after THA using the posterolateral (PL) and anterolateral (AL) approaches. Methods Sixty-four hips in 64 patients who underwent primary THA were retrospectively analyzed. Patients were segregated into the PL group (35 hips) and AL group (29 hips) for evaluating pre- and postoperative muscle volumes and degeneration around the hip. Computed tomography (CT) examinations were performed preoperatively and 6 months post THA. The muscle volume and Hounsfield units (HU) of the gluteus maximus (G-max), gluteus medius (G-med), tensor fasciae latae, internal obturator muscle, and external obturator muscle were measured. Results In the PL group, the postoperative muscle volume of the G-max significantly increased than the preoperative muscle volume. In contrast, the postoperative muscle volume of the internal obturator muscle was significantly lower than the preoperative muscle volume. The postoperative HU of the internal and external obturator muscles were significantly lower than the preoperative HU. In the AL group, the postoperative muscle volumes of the G-max, G-med, and tensor fasciae latae significantly increased than their preoperative muscle volumes. The postoperative HU of the G-med and tensor fasciae latae were significantly higher than the preoperative HU values. Conclusion The PL approach can lead to degeneration of the internal and external obturator. The AL approach is more beneficial for recovering the G-med, tensor fasciae latae, and internal obturator muscle than the PL approach.

Abstract Background The purpose of the study is to investigate the correlation between upper lumbar disc herniation (ULDH) and multifidus muscle degeneration via the comparison of width, the cross-sectional area and degree of fatty infiltration of the lumbar multifidus muscle. Methods Using the axial T2-weighted images of magnetic resonance imaging as an assessment tool, we retrospectively investigated 132 patients with ULDH and 132 healthy individuals. The total muscle cross-sectional area (TMCSA) and the pure muscle cross-sectional area (PMCSA) of the multifidus muscle at the L1/2, L2/3, and L3/4 intervertebral disc levels were measured respectively, and in the meantime, the average multifidus muscle width (AMMW) and degree of fatty infiltration of bilateral multifidus muscle were evaluated. The resulting data were analyzed to determine the presence/absence of statistical significance between the study and control groups. Multivariate logistical regression analyses were used to evaluate the correlation between ULDH and multifidus degeneration. Results The results of the analysis of the two groups showed that there were statistically significant differences (p

Background: Monitoring the fatty infiltration (FI) process in rotator cuff muscles is of value in establishing a treatment plan and predicting the postoperative prognosis. Quantitative T1 mapping shows promise for evaluating muscle degeneration, while its validity in monitoring rotator cuff muscle FI progression needs further investigation. Purpose: To determine the validity of T1 mapping in monitoring FI progression of rotator cuff muscles. Study Design: Controlled laboratory study. Methods: Sprague-Dawley rats (N = 108) underwent left supraspinatus (SS) and infraspinatus (IS) tenotomy only (TT), suprascapular nerve transection only (NT), or SS and IS tenotomy plus suprascapular nerve transection (TT+NT). Sham surgery on the right shoulder served as the control. The magnetic resonance imaging examination included T1 mapping performed at 12, 16, and 20 weeks postoperation. SS and IS muscles were harvested to quantitatively evaluate FI via direct evaluation (triglyceride quantification assay and histological analysis) at the same predetermined intervals. The correlation of the imaging data with direct evaluation of rotator cuff muscles was analyzed. Results: T1 values were significantly lower in left SS and IS muscles at 12, 16, and 20 weeks postoperation as compared with those on the right side. T1 values of the left SS and IS muscles were continuously decreased in all groups. The TT+NT group had a greater decrease in T1 value than did the TT and NT groups. Triglyceride quantification assay and histological analysis demonstrated significant and progressive FI of the left SS and IS muscles in the 3 groups. The most serious FI changes were observed in the TT+NT group. T1 values were also well correlated with triglyceride contents and area fractions of fat. Conclusion: T1 mapping can be an effective imaging modality for sensitive and quantitative monitoring of FI progression in rotator cuff muscles. Clinical Relevance: The findings of this study provide a tool for researchers to noninvasively and quantitatively monitor the process of muscle degeneration, contributing to the evaluation of surgical indication and postoperative prognosis. [ABSTRACT FROM AUTHOR]

The rabbit supraspinatus is a useful translational model for rotator cuff (RC) repair because it recapitulates muscle atrophy and fat accumulation observed in humans after a chronic tear (the "first hit"). However, a timeline of RC tissue response after repair, especially with regard to recent evidence of muscle degeneration and lack of regeneration, is currently unavailable. Thus, the purpose of this study was to characterize the progression of muscle and fat changes over time after the repair of a chronic RC tear in the rabbit model. Two rounds of experiments were conducted in 2017–2018 and 2019–2020 with N = 18 and 16 skeletally mature New Zealand White rabbits, respectively. Animals underwent left supraspinatus tenotomy with repair 8 weeks later. The unoperated right shoulder served as control. The rabbits were sacrificed at 1-, 2-, 4-, and 8-weeks post-repair for histological and biochemical analysis. Atrophy, measured by fiber cross-sectional area and muscle mass, was greatest around 2 weeks after repair. Active muscle degeneration peaked at the same time, involving 8% of slide areas. There was no significant regeneration at any timepoint. Fat accumulation and fibrosis were significantly increased across all time points compared to contralateral. Statement of Clinical Significance: These results demonstrate model reproducibility and a "second hit" phenomenon of repair-induced muscle atrophy and degeneration which partially recovers after a short time, while increased fat and fibrosis persist. [ABSTRACT FROM AUTHOR]

Several scientific evidence have shown that exposure to microgravity has a significant impact on the health of the musculoskeletal system by altering the expression of proteins and molecules involved in bone–muscle crosstalk, which is also observed in the research of microgravity effect simulation. Among these, the expression pattern of myostatin appears to play a key role in both load-free muscle damage and the progression of age-related musculoskeletal disorders, such as osteoporosis and sarcopenia. Based on this evidence, we here investigated the efficacy of treatment with anti-myostatin (anti-MSTN) antibodies on primary cultures of human satellite cells exposed to 72 h of random positioning machine (RPM). Cell cultures were obtained from muscle biopsies taken from a total of 30 patients (controls, osteoarthritic, and osteoporotic) during hip arthroplasty. The Pax7 expression by immunofluorescence was carried out for the characterization of satellite cells. We then performed morphological evaluation by light microscopy and immunocytochemical analysis to assess myostatin expression. Our results showed that prolonged RPM exposure not only caused satellite cell death, but also induced changes in myostatin expression levels with group-dependent variations. Surprisingly, we observed that the use of anti-MSTN antibodies induced a significant increase in cell survival after RPM exposure under all experimental conditions. Noteworthy, we found that the negative effect of RPM exposure was counteracted by treatment with anti-MSTN antibodies, which allowed the formation of numerous myotubes. Our results highlight the role of myostatin as a major effector of the cellular degeneration observed with RPM exposure, suggesting it as a potential therapeutic target to slow the muscle mass loss that occurs in the absence of loading. [ABSTRACT FROM AUTHOR]

Abstract Background Late‐onset Pompe disease (LOPD) is a genetic disorder characterized by progressive degeneration of the skeletal muscles produced by a deficiency of the enzyme acid alpha‐glucosidase. Enzymatic replacement therapy with recombinant human alpha‐glucosidase seems to reduce the progression of the disease; although at the moment, it is not completely clear to what extent. Quantitative muscle magnetic resonance imaging (qMRI) is a good biomarker for the follow‐up of fat replacement in neuromuscular disorders. The aim of this study was to describe the changes observed in fat replacement in skeletal muscles using qMRI in a cohort of LOPD patients followed prospectively. Methods A total of 36 LOPD patients were seen once every year for 4 years. qMRI, several muscle function tests, spirometry, activities of daily living scales, and quality‐of‐life scales were performed on each visit. Muscle MRI consisted of two‐point Dixon studies of the trunk and thigh muscles. Computer analysis of the images provided the percentage of muscle degenerated and replaced by fat in every muscle (known as fat fraction). Longitudinal analysis of the measures was performed using linear mixed models applying the Greenhouse–Geisser test. Results We detected a statistically significant and continuous increase in mean thigh fat fraction both in treated (+5.8% in 3 years) and in pre‐symptomatic patients (+2.6% in 3years) (Greenhouse–Geisser p < 0.05). As an average, fat fraction increased by 1.9% per year in treated patients, compared with 0.8% in pre‐symptomatic patients. Fat fraction significantly increased in every muscle of the thighs. We observed a significant correlation between changes observed in fat fraction in qMRI and changes observed in the results of the muscle function tests performed. Moreover, we identified that muscle performance and mean thigh fat fraction at baseline visit were independent parameters influencing fat fraction progression over 4 years (analysis of covariance, p < 0.05). Conclusions Our study identifies that skeletal muscle fat fraction continues to increase in patients with LOPD despite the treatment with enzymatic replacement therapy. These results suggest that the process of muscle degeneration is not stopped by the treatment and could impact muscle function over the years. Hereby, we show that fat fraction along with muscle function tests can be considered a good outcome measures for clinical trials in LOPD patients.

Purpose: Double ipsilateral inguinal (“pantaloon”) hernias and also the more advanced “combined” inguinal hernia involve disruption of the inguinal floor. In the case of pantaloon hernias, the medial boundary of the internal ring remains intact but in combined hernias this is fully disrupted, producing a single hernial protrusion. Deepening the pathophysiology of these hernias may be helpful in addressing hernia genesis, thus improving strategies for the treatment of this disease. Materials and Methods: A cohort of 22 patients who underwent inguinal hernia repair showed double ipsilateral (pantaloon) hernia, comprising distinct direct and indirect protrusions separated by a tissue septum. In 19 patients, the septal arrangement dividing the 2 hernias showed macroscopically evident structural damages, then excised and histologically studied. Different tissue markers were used for the identification of the structural damages. Results: Macroscopically, the divisor septum represents the boundary between internal ring and Hesselbach’s triangle. Anteriorly it is composed by fibers of the internal oblique and transverse muscles, which form a complex with the inferior epigastric vessels on the corresponding posterior side of the inguinal floor. In the patient cohort studied, this anatomical structure showed a progressive sufferance characterized by chronic compressive damage. Conclusion: The anatomical structure which separates the indirect and direct components of a pantaloon hernia, herein referred to as the “septum inguinalis”, has been shown progressively alter in both macro- and microscopically until it f undergoes disruption with development of a combined hernia. Understanding of this anatomical concept may help surgeons to perform sound repairs of these complex hernias.

The rabbit supraspinatus is a useful translational model for rotator cuff (RC) repair because it recapitulates muscle atrophy and fat accumulation observed in humans after a chronic tear (the “first hit”). However, a timeline of RC tissue response after repair, especially with regard to recent evidence of muscle degeneration and lack of regeneration, is currently unavailable. Thus, the purpose of this study was to characterize the progression of muscle and fat changes over time after the repair of a chronic RC tear in the rabbit model. Two rounds of experiments were conducted in 2017–2018 and 2019–2020 with N = 18 and 16 skeletally mature New Zealand White rabbits, respectively. Animals underwent left supraspinatus tenotomy with repair 8 weeks later. The unoperated right shoulder served as control. The rabbits were sacrificed at 1-, 2-, 4-, and 8-weeks post-repair for histological and biochemical analysis. Atrophy, measured by fiber cross-sectional area and muscle mass, was greatest around 2 weeks after repair. Active muscle degeneration peaked at the same time, involving 8% of slide areas. There was no significant regeneration at any timepoint. Fat accumulation and fibrosis were significantly increased across all time points compared to contralateral. Statement of Clinical Significance: These results demonstrate model reproducibility and a “second hit” phenomenon of repair-induced muscle atrophy and degeneration which partially recovers after a short time, while increased fat and fibrosis persist.

Several scientific evidence have shown that exposure to microgravity has a significant impact on the health of the musculoskeletal system by altering the expression of proteins and molecules involved in bone–muscle crosstalk, which is also observed in the research of microgravity effect simulation. Among these, the expression pattern of myostatin appears to play a key role in both load-free muscle damage and the progression of age-related musculoskeletal disorders, such as osteoporosis and sarcopenia. Based on this evidence, we here investigated the efficacy of treatment with anti-myostatin (anti-MSTN) antibodies on primary cultures of human satellite cells exposed to 72 h of random positioning machine (RPM). Cell cultures were obtained from muscle biopsies taken from a total of 30 patients (controls, osteoarthritic, and osteoporotic) during hip arthroplasty. The Pax7 expression by immunofluorescence was carried out for the characterization of satellite cells. We then performed morphological evaluation by light microscopy and immunocytochemical analysis to assess myostatin expression. Our results showed that prolonged RPM exposure not only caused satellite cell death, but also induced changes in myostatin expression levels with group-dependent variations. Surprisingly, we observed that the use of anti-MSTN antibodies induced a significant increase in cell survival after RPM exposure under all experimental conditions. Noteworthy, we found that the negative effect of RPM exposure was counteracted by treatment with anti-MSTN antibodies, which allowed the formation of numerous myotubes. Our results highlight the role of myostatin as a major effector of the cellular degeneration observed with RPM exposure, suggesting it as a potential therapeutic target to slow the muscle mass loss that occurs in the absence of loading.

Acute localized irradiation accidents may evolve into a musculocutaneous radiation-induced syndrome that leaves a significant underlying muscle defect despite standard treatment. The identification of new therapeutic targets is, therefore, necessary to improve post-irradiation muscle repair. Thus, the validation of an in vivo model of radiation-induced muscle injury has been initiated in C57Bl/6J mice. In the model presented in this study, the high-dose ionizing radiation exposure is focused on gastrocnemius and soleus muscles, does not affect bones, and is a part of hindlimb vascularization. It aims at identifying original metabolic pathways specifically involved in muscle damage and evaluating innovative therapeutic strategies.

A recessive X-linked illness called Duchenne muscular dystrophy (DMD) is characterized by increasing muscle weakening and degradation. It primarily affects boys and is one of the most prevalent and severe forms of muscular dystrophy. Mutations in the DMD gene, which codes for the essential protein dystrophin, which aids in maintaining the stability of muscle cell membranes during contraction, are the cause of the illness. Dystrophin deficiency or malfunction damages muscle cells, resulting in persistent inflammation and progressive loss of muscular mass. The pathophysiology and genetic foundation of DMD are thoroughly examined in this review paper, focusing on the function of the NF-κB signaling system in the disease's progression. An important immune response regulator, NF-κB, is aberrantly activated in DMD, which exacerbates the inflammatory milieu in dystrophic muscles. Muscle injury and fibrosis are exacerbated and muscle regeneration is hampered by the pro-inflammatory cytokines and chemokines that are produced when NF-κB is persistently activated in muscle cells. The paper also examines our existing knowledge of treatment approaches meant to inhibit the progression of disease by modifying NF-κB signaling. These include new molecular techniques, gene treatments, and pharmacological inhibitors that are intended to lessen inflammation and improve muscle healing. Furthermore covered in the analysis is the significance of supportive care for DMD patients, including physical therapy and corticosteroid treatment, in symptom management and quality of life enhancement. The article seeks to provide a thorough understanding of the mechanisms causing DMD, possible therapeutic targets, and developing treatment options by combining recent research findings. This will provide clinicians and researchers involved in DMD care and research with invaluable insights., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, R et al.)

Duchenne muscular dystrophy is a highly progressive muscle wasting disorder due to primary abnormalities in one of the largest genes in the human genome, the DMD gene, which encodes various tissue-specific isoforms of the protein dystrophin. Although dystrophinopathies are classified as primary neuromuscular disorders, the body-wide abnormalities that are associated with this disorder and the occurrence of organ crosstalk suggest that a multi-systems pathophysiological view should be taken for a better overall understanding of the complex aetiology of X-linked muscular dystrophy. This article reviews the molecular and cellular effects of deficiency in dystrophin isoforms in relation to voluntary striated muscles, the cardio-respiratory system, the kidney, the liver, the gastrointestinal tract, the nervous system and the immune system. Based on the establishment of comprehensive biomarker signatures of X-linked muscular dystrophy using large-scale screening of both patient specimens and genetic animal models, this article also discusses the potential usefulness of novel disease markers for more inclusive approaches to differential diagnosis, prognosis and therapy monitoring that also take into account multi-systems aspects of dystrophinopathy. Current therapeutic approaches to combat muscular dystrophy are summarised. [ABSTRACT FROM AUTHOR]

Carbonic anhydrase (CA) is a key enzyme that mediates the reversible hydration of carbon dioxide. Skeletal muscles contain high levels of the cytosolic isoform CA3. This enzyme has antioxidative function and plays a crucial role in the maintenance of intracellular pH homeostasis. Since elevated levels of serum CA3, often in combination with other muscle-specific proteins, are routinely used as a marker of general muscle damage, it was of interest to examine recent analyses of this enzyme carried out by modern proteomics. This review summarizes the mass spectrometry-based identification and evaluation of CA3 in normal, adapting, dystrophic, and aging skeletal muscle tissues. The mass spectrometric characterization of CA3 confirmed this enzyme as a highly useful marker of both physiological and pathophysiological alterations in skeletal muscles. Cytosolic CA3 is clearly enriched in slow-twitching type I fibers, which makes it an ideal marker for studying fiber type shifting and muscle adaptations. Importantly, neuromuscular diseases feature distinct alterations in CA3 in skeletal muscle tissues versus biofluids, such as serum. Characteristic changes of CA3 in age-related muscle wasting and dystrophinopathy established this enzyme as a suitable biomarker candidate for differential diagnosis and monitoring of disease progression and therapeutic impact. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Duchenne and Becker muscular dystrophies (DMD and BMD, respectively) are characterized by fat replacement of different skeletal muscles in a specific temporal order. Given the structural role of dystrophin in skeletal muscle mechanics, muscle architecture could be important in the progressive pathophysiology of muscle degeneration. Therefore, the aim of this study was to assess the role of muscle architecture in the progression of fat replacement in DMD and BMD. Methods: We assessed the association between literature‐based leg muscle architectural characteristics and muscle fat fraction from 22 DMD and 24 BMD patients. Dixon‐based magnetic resonance imaging estimates of fat fractions at baseline and 12 (only DMD) and 24 months were related to fiber length and physiological cross‐sectional area (PCSA) using age‐controlled linear mixed modeling. Results: DMD and BMD muscles with long fibers and BMD muscles with large PCSAs were associated with increased fat fraction. The effect of fiber length was stronger in muscles with larger PCSA. Discussion: Muscle architecture may explain the pathophysiology of muscle degeneration in dystrophinopathies, in which proximal muscles with a larger mass (fiber length × PCSA) are more susceptible, confirming the clinical observation of a temporal proximal‐to‐distal progression. These results give more insight into the mechanical role in the pathophysiology of muscular dystrophies. Ultimately, this new information can be used to help support the selection of current and the development of future therapies. [ABSTRACT FROM AUTHOR]

Aim: To compare therapeutic benefits of different immunophilin ligands for treating nerve injuries. Materials & methods: Cyclosporine, FK506 and rapamycin, were evaluated first in vitro on a serum-free culture of embryonic dorsal root ganglia followed by a new in vivo model of chronic nerve compression. Results: Outcomes of the in vitro study have shown a potent effect of cyclosporine and FK506, on dorsal root ganglia axonal outgrowth, comparable to the effect of nerve growth factor. Rapamycin exhibited only a moderate effect. The in vivo study revealed the beneficial effects of cyclosporine, FK506 and rapamycin for neuromuscular regeneration. Cyclosporine showed the better maintenance of the tissues and function. Conclusion: Cyclosporine, FK506 and rapamycin drugs showed potential for treating peripheral nerve chronic compression injuries. [ABSTRACT FROM AUTHOR]