Article
Biochemistry & Molecular Biology
Bo Song, Yating Cheng, Md. Abul Kalam Azad, Sujuan Ding, Kang Yao, Xiangfeng Kong
Summary: This study investigated the molecular basis for differences in meat yield and quality between Duroc, Taoyuan black (TB), and Xiangcun black (XB) pigs. The results show that TB pigs have higher fat percentage, intramuscular fat content, and antioxidant capacity, but lower carcass weight, lean percentage, pH decline, and glycolytic potential compared to Duroc pigs. Moreover, TB pigs have lower expression of protein synthesis and lipolysis genes in their muscles. Targeted metabolome analysis revealed significant differences in 24 metabolites among the three pig breeds. Correlation analysis suggests that l-malic acid and β-alanine contents in muscles are closely related to meat quality. These findings suggest that the excellent meat quality of TB pigs is attributed to muscle metabolism and fiber characteristics, while lower protein synthesis and lipolysis contribute to less meat yield.
Article
Multidisciplinary Sciences
Michael J. Stec, Qi Su, Christina Adler, Lance Zhang, David R. Golann, Naveen P. Khan, Lampros Panagis, S. Armando Villalta, Min Ni, Yi Wei, Johnathon R. Walls, Andrew J. Murphy, George D. Yancopoulos, Gurinder S. Atwal, Sandra Kleiner, Gabor Halasz, Mark W. Sleeman
Summary: Using spatial transcriptomics and single-cell RNA sequencing datasets, a high-resolution cellular and molecular spatial atlas of the severely dystrophic D2-mdx mouse model was generated. Clustering analysis revealed the nonuniform distribution of unique cell populations associated with multiple regenerative timepoints, faithfully recapitulating the asynchronous regeneration observed in human DMD muscle. Through spatiotemporal gene expression signatures, it was found that propagation of inflammatory and fibrotic signals from locally damaged areas contributes to widespread pathology and identifying targetable pathways for DMD therapy within discrete microenvironments. Overall, this spatial atlas of dystrophic muscle provides a valuable resource for studying DMD disease biology and therapeutic target discovery.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Zsofia Onodi, Petra Lujza Szabo, Daniel Kucsera, Peter Pokreisz, Christopher Dostal, Karlheinz Hilber, Gavin Y. Oudit, Bruno K. Podesser, Peter Ferdinandy, Zoltan V. Varga, Attila Kiss
Summary: Duchenne muscular dystrophy (DMD) is a muscle wasting disease characterized by difficulty moving and premature death, mainly due to heart failure. Inflammation is thought to play a role in the disease progression, but the specific mechanisms are not well understood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Stephen Gargan, Paul Dowling, Margit Zweyer, Jens Reimann, Michael Henry, Paula Meleady, Dieter Swandulla, Kay Ohlendieck
Summary: The study of EOM proteomics in dystrophinopathy revealed abnormal expression levels of contractile proteins and adaptation through metabolic shifts and cellular stress responses.
Article
Geriatrics & Gerontology
Mina Shahriyari, Md Rezaul Islam, Sadman M. Sakib, Malte Rinn, Anastasia Rika, Dennis Krueger, Lalit Kaurani, Verena Gisa, Mandy Winterhoff, Harithaa Anandakumar, Orr Shomroni, Matthias Schmidt, Gabriela Salinas, Andreas Unger, Wolfgang A. Linke, Jana Zschuentzsch, Jens Schmidt, Rhonda Bassel-Duby, Eric N. Olson, Andre Fischer, Wolfram-Hubertus Zimmermann, Malte Tiburcy
Summary: This study successfully established methods for deriving skeletal muscle cells from human pluripotent stem cells and engineered a functional human skeletal muscle organoid and engineered skeletal muscle with regeneration-competent satellite-like cells. Contractile performance of the engineered muscle was further enhanced by thyroid hormone treatment.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Review
Biochemistry & Molecular Biology
Gabryela Kuhnen, Tiago Guedes Russomanno, Marta Murgia, Nicolas J. Pillon, Martin Schoenfelder, Henning Wackerhage
Summary: Adult skeletal muscle fibres can be classified into different types based on the expression of specific genes. The proportions of these muscle fibre types can be altered through gene gain or loss-of-function. In particular, transcriptional regulators play a significant role in regulating the expression of muscle fibre-specific genes. After exercise, the expression of certain genes increases or decreases, suggesting their involvement in muscle fibre adaptation. DNA sequence variants of muscle fibre genes may contribute to the variation in muscle fibre type proportions in the human population.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Physiology
Kasun Kodippili, Michael A. Rudnicki
Summary: Progressive muscle weakness and degeneration are characteristic of Duchenne muscular dystrophy (DMD), a fatal, x-linked neuromuscular disorder affecting 1 in 5,000 boys. Loss of dystrophin protein results in recurrent muscle degeneration, progressive fibrosis, chronic inflammation, and dysfunction of satellite cells, which are skeletal muscle resident stem cells. Currently, there is no cure for DMD. This mini review discusses the impaired functionality of satellite cells in dystrophic muscle, its contribution to DMD pathology, and the potential of restoring endogenous satellite cell function as a viable treatment strategy.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sharon Mordechay, Shaun Smullen, Paul Evans, Olga Genin, Mark Pines, Orna Halevy
Summary: The study showed that the enantiomers of halofuginone had differential effects on motor coordination and muscle histopathology in mdx mice, with (+)-halofuginone being the most effective. These findings suggest a potential use for (+)-halofuginone as a therapy for DMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Physiology
Angus Lindsay, Bailey Kemp, Alexie A. Larson, Cory W. Baumann, Preston M. McCourt, John Holm, Peter Karachunski, Dawn A. Lowe, James M. Ervasti
Summary: The study found that levels of tetrahydrobiopterin were low in Duchenne muscular dystrophy patients and mdx mice, but could be restored to normal levels by overexpressing dystrophin. Tetrahydrobiopterin deficiency in mdx mice was likely due to lower levels of sepiapterin reductase in skeletal muscle. Supplementation with tetrahydrobiopterin improved skeletal muscle function and cardiac pathology in mdx mice.
Review
Physiology
Addeli Bez Batti Angulski, Nora Hosny, Houda Cohen, Ashley A. Martin, Dongwoo Hahn, Jack Bauer, Joseph M. Metzger
Summary: Duchenne muscular dystrophy (DMD) is a severe and fatal disease characterized by muscle wasting, respiratory insufficiency, and cardiomyopathy. The dystrophin gene plays a central role in the pathogenesis of DMD, with the muscle membrane and associated proteins being key components. This review examines the pathophysiology of DMD, current therapeutic strategies, and ongoing clinical trials for the treatment of this devastating disease.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Cell Biology
Elisia D. Tichy, Nuoying Ma, David Sidibe, Emanuele Loro, Jacob Kocan, Delia Z. Chen, Tejvir S. Khurana, Paul Hasty, Foteini Mourkioti
Summary: Repeated cycles of damage and repair in muscle disorders like DMD can lead to inefficiency in muscle stem cell response. The early telomere shortening in diseased MuSCs is associated with aberrant NF-kappa B activation, leading to severe skeletal muscle defects. NF-kappa B plays a role in regulating stem-cell-specific telomere length and could be a common mechanism in diseases characterized by chronic inflammation.
Article
Immunology
Brigida Boccanegra, Ornella Cappellari, Paola Mantuano, Daniela Trisciuzzi, Antonietta Mele, Lisamaura Tulimiero, Michela De Bellis, Santa Cirmi, Francesca Sanarica, Alessandro Giovanni Cerchiara, Elena Conte, Ramona Meanti, Laura Rizzi, Elena Bresciani, Severine Denoyelle, Jean-Alain Fehrentz, Gabriele Cruciani, Orazio Nicolotti, Antonella Liantonio, Antonio Torsello, Annamaria De Luca
Summary: Growth hormone secretagogues (GHSs) have multiple actions including activation of GHS-receptor 1a, control of inflammation and metabolism, enhancement of GH/IGF-1-mediated myogenesis, and inhibition of angiotensin-converting enzyme. This study provides preclinical evidence for the potential benefits of GHSs in Duchenne muscular dystrophy (DMD). The results show that GHSs can improve muscle strength, reduce fibrosis-related parameters, and improve muscle metabolism in mdx mice, suggesting that GHSs have potential as therapeutic agents for DMD.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Angus Lindsay, John Holm, Maria Razzoli, Alessandro Bartolomucci, James M. Ervasti, Dawn A. Lowe
Summary: Research shows that mdx mice do not habituate to mild stress, and daily exposure to mild stress for weeks exacerbates phenotypes associated with dystrophinopathy in mdx mice.
Article
Engineering, Biomedical
Ioannis Eugenis, Di Wu, Thomas A. Rando
Summary: The paper discusses tissue engineering strategies for VML, including cell therapy, scaffold design, and bioactive factor delivery. It also addresses the limitations of current advanced technologies and the prospects of tissue-engineered bioconstructs for muscle regeneration and functional recovery following VML.
Article
Biochemistry & Molecular Biology
Yuri Fujikura, Hidetoshi Sugihara, Masaki Hatakeyama, Katsutaka Oishi, Keitaro Yamanouchi
Summary: A study showed that a ketogenic diet with medium-chain triglycerides (MCT-KD) significantly improved genetically mutated Duchenne muscular dystrophy in model rats by increasing muscle strength and fiber diameter, suppressing muscle necrosis, inflammation, and fibrosis, promoting the proliferation of muscle satellite cells, and improving muscle strength even at the age of 9 months. Further research is needed to understand the mechanisms underlying the improvement of Duchenne muscular dystrophy induced by MCT-KD.
Meeting Abstract
Orthopedics
Y. -H. Chen, C-H. Chou, A. Khodabukus, N. Bursac, G. Truskey, W. Kraus, V. B. Kraus
OSTEOARTHRITIS AND CARTILAGE
(2018)
Article
Multidisciplinary Sciences
Lingjun Rao, Ying Qian, Alastair Khodabukus, Thomas Ribar, Nenad Bursac
NATURE COMMUNICATIONS
(2018)
Review
Engineering, Biomedical
Alastair Khodabukus, Neel Prabhu, Jason Wang, Nenad Bursac
ADVANCED HEALTHCARE MATERIALS
(2018)
Article
Engineering, Biomedical
Alastair Khodabukus, Lauran Madden, Neel K. Prabhu, Timothy R. Koves, Christopher P. Jackman, Deborah M. Muoio, Nenad Bursac
Review
Engineering, Biomedical
Jason Wang, Alastair Khodabukus, Lingjun Rao, Keith Vandusen, Nadia Abutaleb, Nenad Bursac
Editorial Material
Pharmacology & Pharmacy
Torie Broer, Alastair Khodabukus, Nenad Bursac
EXPERT OPINION ON DRUG DISCOVERY
(2020)
Article
Cell & Tissue Engineering
Megan E. Kondash, Anandita Ananthakumar, Alastair Khodabukus, Nenad Bursac, George A. Truskey
TISSUE ENGINEERING AND REGENERATIVE MEDICINE
(2020)
Article
Toxicology
Alastair Khodabukus, Amulya Kaza, Jason Wang, Neel Prabhu, Richard Goldstein, Vishal S. Vaidya, Nenad Bursac
TOXICOLOGICAL SCIENCES
(2020)
Article
Biology
Jason Wang, Chris J. Zhou, Alastair Khodabukus, Sabrina Tran, Sang-Oh Han, Aaron L. Carlson, Lauran Madden, Priya S. Kishnani, Dwight D. Koeberl, Nenad Bursac
Summary: The study developed a 3D in vitro model of human skeletal muscle that recapitulates the pathophysiology of Pompe disease. They identified a Pompe disease-specific transcriptional signature and observed a partial reversal of the signature upon in vitro treatment of myobundles with rhGAA.
COMMUNICATIONS BIOLOGY
(2021)
Review
Cell Biology
Zachary Fralish, Ethan M. Lotz, Taylor Chavez, Alastair Khodabukus, Nenad Bursac
Summary: The neuromuscular junction (NMJ) is a crucial interface between motor neurons and skeletal muscle fibers that is essential for motor function. This review discusses the development of in vitro models of human NMJs derived from induced pluripotent stem cells (hiPSCs) and compares the efficacy of modeling neuromuscular diseases (NMDs) in animals and cell culture systems. Further research is needed to develop effective personalized NMD platforms using hiPSC-derived NMJ models.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Engineering, Biomedical
Jason Wang, Torie Broer, Taylor Chavez, Chris J. Zhou, Sabrina Tran, Yu Xiang, Alastair Khodabukus, Yarui Diao, Nenad Bursac
Summary: This study optimized the methods for deactivating in vitro expanded human myoblasts within a 3D culture of engineered human skeletal muscle tissues. The results showed that a fraction of myoblasts within the culture adopted a quiescent phenotype similar to native satellite cells, and could be reactivated. Single cell RNA-sequencing revealed the existence of two subpopulations of these quiescent and activated cells, and characterized their gene expression changes. This study provides a platform for further research on human muscle regeneration and disease-associated satellite cell dysfunction.
Review
Cell Biology
Alastair Khodabukus, Tyler Guyer, Axel C. Moore, Molly M. Stevens, Robert E. Guldberg, Nenad Bursac
Summary: Musculoskeletal injuries and disorders are the main cause of physical disability globally, posing a significant socioeconomic burden. The lack of effective treatments has led to the development of novel bioengineering approaches. This review discusses the self-repair capacity of musculoskeletal tissues, the causes of musculoskeletal dysfunction, and the advancements in biomaterial, immunomodulatory, cellular, and gene therapies for treating musculoskeletal disorders.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Physiology
Christopher G. Vann, Xin Zhang, Alastair Khodabukus, Melissa C. C. Orenduff, Yu-Hsiu Chen, David L. L. Corcoran, George A. A. Truskey, Nenad Bursac, Virginia B. B. Kraus
Summary: Exercise-mimetic contractile activity of human engineered muscle affects the expression of miRs and the number of secreted EVs, providing new insights into the role of exercise in organ-organ interactions.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
David E. Lee, Lauren K. McKay, Akshay Bareja, Yongwu Li, Alastair Khodabukus, Nenad Bursac, Gregory A. Taylor, Gurpreet S. Baht, James P. White
Summary: Pathologies associated with sarcopenia include decline in muscular strength, lean mass and regenerative capacity. This study investigates the therapeutic potential of METRNL to improve aged muscle through improving muscle regeneration and countering age-related loss in muscle resilience by triggering apoptosis of fibro/adipogenic progenitor cells.
NATURE COMMUNICATIONS
(2022)