Article
Biochemistry & Molecular Biology
Agnese Bonato, Giada Raparelli, Siro Luvisetto, Flavia Forconi, Marianna Cosentino, Felice Tirone, Emanuele Rizzuto, Maurizia Caruso
Summary: We found that cyclin D3-null mice exhibit a shift towards oxidative muscle fibers and improved endurance in response to exercise, as well as enhanced response to fasting. In a model of Duchenne muscular dystrophy (DMD), cyclin D3-deficient mice displayed a higher proportion of oxidative fibers, reduced muscle degeneration/regeneration, and reduced muscle fatigue. This suggests that depletion of cyclin D3 may be a promising therapeutic strategy against DMD.
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
Biochemistry & Molecular Biology
Keryn G. Woodman, Chantal A. Coles, Shireen R. Lamande, Jason D. White
Summary: Resveratrol at a lower dosage showed potential efficacy in reducing muscle damage and inflammatory cell markers associated with Duchenne muscular dystrophy, suggesting it as a candidate drug for treating DMD.
Article
Cell Biology
Davi A. G. Mazala, Ravi Hindupur, Young Jae Moon, Fatima Shaikh, Iteoluwakishi H. Gamu, Dhruv Alladi, Georgiana Panci, Michele Weiss-Gayet, Benedicte Chazaud, Terence A. Partridge, James S. Novak, Jyoti K. Jaiswal
Summary: Lack of dystrophin expression is the genetic basis for Duchenne muscular dystrophy (DMD), and disease severity varies due to genetic modifiers. The D2-mdx model exhibits severe muscle degeneration and poor regeneration in juvenile stage, resulting from an enhanced inflammatory response and excessive accumulation of fibroadipogenic progenitors (FAPs). However, in adult D2-mdx muscle, the extent of damage and degeneration decreases, associated with restoration of inflammatory and FAP responses, leading to improved regenerative myogenesis. Therefore, targeting aberrant stromal cell responses may provide therapeutic benefits for DMD treatment.
CELL DEATH DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Yazmin I. Rovira Gonzalez, Adam L. Moyer, Nicolas J. LeTexier, August D. Bratti, Siyuan Feng, Vanessa Pena, Congshan Sun, Hannah Pulcastro, Ting Liu, Shama R. Iyer, Richard M. Lovering, Brian O'Rourke, Kathryn R. Wagner
Summary: The study found that deletion of Mss51 in the mdx murine model of Duchenne muscular dystrophy (mdx-Mss51 KO) improved muscle histopathology and increased myofiber oxygen consumption rates. However, while mdx-Mss51 KO mice showed greater treadmill endurance and less fatigue in muscle physiology, there was no improvement in forelimb grip strength or limb muscle force production.
Article
Cell Biology
Rekha Balakrishnan, Satvik Mareedu, Gopal J. Babu
Summary: The reduction or elimination of sarcolipin (SLN) expression improves muscle metabolism, reduces oxidative stress, improves muscle pathology, and protects mdx mice from glucose intolerance in the Duchenne muscular dystrophy (DMD) mouse model.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Michael Ziemba, Molly Barkhouse, Kitipong Uaesoontrachoon, Mamta Giri, Yetrib Hathout, Utkarsh J. Dang, Heather Gordish-Dressman, Kanneboyina Nagaraju, Eric P. Hoffman
Summary: Duchenne muscular dystrophy is caused by dystrophin deficiency, leading to downstream pathophysiological pathways that drive disability. Dystrophin replacement strategies may trigger these pathways, so combination therapies targeting multiple downstream pathways are crucial. Blood biomarkers could be used to assess drug combinations for treating DMD in both mouse models and human studies.
Article
Biochemistry & Molecular Biology
Daria De Giorgio, Deborah Novelli, Francesca Motta, Marianna Cerrato, Davide Olivari, Annasimon Salama, Francesca Fumagalli, Roberto Latini, Lidia Staszewsky, Luca Crippa, Christian Steinkuhler, Simonetta Andrea Licandro
Summary: Duchenne muscular dystrophy (DMD) is a common hereditary disease characterized by muscle degeneration. This study focused on D2-mdx mice as a model for DMD cardiomyopathy. The researchers found mild to moderate left ventricle remodeling, increased pulmonary vascular resistance, and prominent epicardial fibrosis in the right ventricle of these mice. The study highlights the need for further long-term investigation to determine if this model accurately represents DMD cardiomyopathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Paul Ritter, Stefanie Nuebler, Andreas Buttgereit, Lucas R. Smith, Alexander Muhlberg, Julian Bauer, Mena Michael, Lucas Kreiss, Michael Haug, Elisabeth Barton, Oliver Friedrich
Summary: This study found that the mdx Cmah (-/-) genotype replicated DMD-like fibrosis but was not associated with changes in passive visco-elastic muscle stiffness. Detriments in active isometric force were compatible with the pronounced myofibrillar disarray of the dystrophic background.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Matteo Giovarelli, Francesca Arnaboldi, Silvia Zecchini, Laura Brigida Cornaghi, Ambra Nava, Michele Sommariva, Emilio Giuseppe Ignazio Clementi, Nicoletta Gagliano
Summary: This study provides a comprehensive histological and molecular characterization of muscle fibrosis in Duchenne muscular dystrophy (DMD), showing that fibrosis mainly affects the diaphragm and quadriceps with higher collagen cross-linking and inhibition of MMPs. These findings may lead to new targeted therapeutic interventions for DMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Developmental Biology
Marine Theret, Lucas Rempel, Joshua Hashimoto, Morten Ritso, Lin Wei Tung, Fang Fang Li, Melina Messing, Michael Hughes, Kelly McNagny, Fabio Rossi
Summary: Eosinophils play important roles in anti-parasitic responses and have recently been found to actively participate in tissue homeostasis and repair. In skeletal muscle, eosinophils support muscle stem cell proliferation after acute damage. However, their role in muscular dystrophy is still unclear.
Article
Materials Science, Multidisciplinary
Giovana Zerbo Martinez, Bruna Alexia Cristofoletti Grillo, Lara Caetano Rocha, Carolina dos Santos Jacob, Jurandyr Pimentel Neto, Andre Neri Tomiate, Gabriela Klein Barbosa, Ii-sei Watanabe, Adriano Polican Ciena
Summary: The study revealed that mdx mice demonstrated extensive impairment in the myotendinous junction (MTJ) region, with shorter sarcomeres, fewer sarcoplasmic projections, and increased deposition of type III collagen.
MICROSCOPY AND MICROANALYSIS
(2021)
Article
Engineering, Biomedical
Kelley M. Virgilio, Brian K. Jones, Emily Y. Miller, Elnaz Ghajar-Rahimi, Kyle S. Martin, Shayn M. Peirce, Silvia S. Blemker
Summary: This study utilized an agent-based model to predict the impact of increased fibrosis on muscle regeneration, and experimentally validated the model-derived hypothesis. The findings suggest that increasing the area fraction of fibrosis alone is not enough to reduce the regenerative capacity of mdx muscle, indicating that fibrosis is a complex pathological condition that requires further understanding.
ANNALS OF BIOMEDICAL ENGINEERING
(2021)
Article
Biochemistry & Molecular Biology
Marco Ponzetti, Argia Ucci, Antonio Maurizi, Luca Giacchi, Anna Teti, Nadia Rucci
Summary: The study found that Lcn2 plays a significant role in DMD, with its overexpression being associated with bone loss. Ablating Lcn2 can reduce bone loss and improve muscle function, making it a potential therapeutic target for treating DMD-induced bone loss.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Michelle Wehling-Henricks, Steven S. Welc, Guiseppina Samengo, Chiara Rinaldi, Catherine Lindsey, Ying Wang, Jeongyoon Lee, Makoto Kuro-O, James G. Tidball
HUMAN MOLECULAR GENETICS
(2018)
Article
Cell Biology
Ying Wang, Steven S. Welc, Michelle Wehling-Henricks, James G. Tidball
Article
Biochemistry & Molecular Biology
Ying Wang, Michelle Wehling-Henricks, Steven S. Welc, Allison L. Fisher, Qun Zuo, James G. Tidball
Article
Multidisciplinary Sciences
Steven S. Welc, Ivan Flores, Michelle Wehling-Henricks, Julian Ramos, Ying Wang, Carmen Bertoni, James G. Tidball
NATURE COMMUNICATIONS
(2019)
Article
Physiology
Steven S. Welc, Michelle Wehling-Henricks, Makoto Kuro-o, Kyle A. Thomas, James G. Tidball
EXPERIMENTAL PHYSIOLOGY
(2020)
Article
Gastroenterology & Hepatology
Yujiro Hayashi, David T. Asuzu, Michael R. Bardsley, Gabriella B. Gajdos, Sergiy M. Kvasha, David R. Linden, Rea A. Nagy, Siva Arumugam Saravanaperumal, Sabriya A. Syed, Yoshitaka Toyomasu, Huihuang Yan, Eduardo N. Chini, Simon J. Gibbons, Todd A. Kellogg, Khashayarsha Khazaie, Makoto Kuro-o, Jair Machado Espindola Netto, Mahendra Pal Singh, James G. Tidball, Michelle Wehling-Henricks, Gianrico Farrugia, Tamas Ordog
Summary: The study suggests that with aging, the decrease in ICC cells may lead to gastric dysfunction, possibly due to upregulated TRP53 through canonical Wnt signaling in ICC stem cells. TRP53 induction persistently inhibits cell cycle transitions without activating traditional markers of senescence.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Immunology
Steven S. Welc, Michelle Wehling-Henricks, Jacqueline Antoun, Tracey T. Ha, Isabella Tous, James G. Tidball
JOURNAL OF IMMUNOLOGY
(2020)
Article
Geriatrics & Gerontology
James G. Tidball, Ivan Flores, Steven S. Welc, Michelle Wehling-Henricks, Eisuke Ochi
Summary: The regeneration of skeletal muscle following acute injury is influenced by interactions with immune cells, particularly myeloid cells and lymphoid cells. Aging leads to a decline in the regenerative capacity of muscle, with age-related changes in the immune system affecting the process. Aging immune cells alter their expression of factors that impact the function of muscle stem cells, contributing to defects in muscle regeneration.
EXPERIMENTAL GERONTOLOGY
(2021)
Article
Engineering, Biomedical
Jun Fang, Junren Sia, Jennifer Soto, Pingping Wang, LeeAnn K. Li, Yuan-Yu Hsueh, Raymond Sun, Kym Francis Faull, James G. Tidball, Song Li
Summary: The study demonstrates that selectively expanded myogenic stem cells using a specific small-molecule cocktail can lead to functional muscle regeneration in various mouse models. Additionally, sustained release of the small-molecule cocktail in situ can promote muscle repair by activating and expanding resident satellite cells.
NATURE BIOMEDICAL ENGINEERING
(2021)
Article
Biochemistry & Molecular Biology
Ivan Flores, Steven S. Welc, Michelle Wehling-Henricks, James G. Tidball
Summary: Transgenic LIF delivery mediated by inflammatory cells exerts differential effects on macrophage dispersion and muscle damage in the mdx mouse model of Duchenne muscular dystrophy, depending on the stage of dystrophic pathology.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Cynthia M. McKee, Douglas J. Chapski, Michelle Wehling-Henricks, Manuel Rosa-Garrido, Makoto Kuro-O, Thomas M. Vondriska, James G. Tidball
Summary: This study reveals that modulation of muscle stem cell numbers during early postnatal development has long-term effects on muscle growth. The anti-aging protein Klotho influences myogenesis by increasing satellite cell numbers and influencing the epigenetic regulation of genes involved in myogenesis. Klotho reduces the expression of Jmjd3, leading to decreased expression of Wnt genes and inhibition of canonical Wnt signaling, which delays muscle differentiation.
Article
Cell Biology
Ying Wang, Steven S. Welc, Michelle Wehling-Henricks, Ying Kong, Connor Thomas, Enca Montecino-Rodriguez, Kenneth Dorshkind, James G. Tidball
Summary: Intramuscular macrophages play key roles in regulating skeletal muscle response to injury and disease. Changes in the numbers and phenotype of these macrophages during aging can influence the aging process. A study using a mouse model with a myeloid cell-specific mutation of Spi1 showed that this mutation reduced the numbers of M2 phenotype macrophages in aging muscles, and also reduced age-related muscle fibrosis and sarcopenia. These findings highlight the significance of intramuscular M2-biased macrophages in promoting detrimental, age-related changes in muscle.
Article
Physiology
Eisuke Ochi, Alice Barrington, Michelle Wehling-Henricks, Marcus Avila, Makoto Kuro-o, James G. Tidball
Summary: Research shows that the hormone Klotho inhibits the response of muscles to mechanical loading and exercise, preventing muscle cell differentiation and inhibiting the activation of the canonical Wnt pathway.
EXPERIMENTAL PHYSIOLOGY
(2023)
Article
Physiology
James G. Tidball, Steven S. Welc, Michelle Wehling-Henricks
COMPREHENSIVE PHYSIOLOGY
(2018)
Review
Immunology
James G. Tidball
NATURE REVIEWS IMMUNOLOGY
(2017)