Review
Genetics & Heredity
Catherine L. Omosule, Charlotte L. Phillips
Summary: Myostatin plays a crucial role in muscle morphology and function, cellular differentiation and metabolism, as well as bone integrity and bone cell biology, impacting the pathophysiology of various human diseases. Pharmacological inhibition of myostatin shows promise in improving muscle and bone properties in diseases like osteogenesis imperfecta, osteoporosis, and Duchenne muscular dystrophy, suggesting potential therapeutic applications in the future. However, challenges remain in the translational application of myostatin inhibition in diseases with significant neuromuscular wasting and atrophy, necessitating further exploration and research.
FRONTIERS IN GENETICS
(2021)
Article
Medicine, Research & Experimental
Cedric Happi Mbakam, Joel Rousseau, Yaoyao Lu, Anne Bigot, Kamel Mamchaoui, Vincent Mouly, Jacques P. Tremblay
Summary: In this study, researchers used CRISPR-Cas9 prime editing technology to correct a mutation in the DMD gene, resulting in improved editing efficiency and restoration of dystrophin protein expression. Optimization of the reverse transcription template sequence led to a significant increase in the editing percentage of the target nucleotide.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
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
Clinical Neurology
Giulio Gadaleta, Guido Urbano, Chiara Brusa, Rossella D'Alessandro, Enrica Rolle, Ilaria Cavallina, Alessio Mattei, Fulvia Ribolla, Claudia Raineri, Stefano Pidello, Liliana Vercelli, Federica S. Ricci, Tiziana E. Mongini
Summary: The clinical characteristics of adults with DMD include mechanical ventilation, swallowing and nutritional issues, and bone density alterations. Other issues include respiratory infections, gastrointestinal symptoms, metabolic acidosis, psychiatric symptoms, and chronic pain. Patients have a negative perception of their physical health but a more positive assessment of their mental health.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Endocrinology & Metabolism
Leanne M. Ward, Anup Choudhury, Nathalie Alos, David A. Cabral, Celia Rodd, Anne Marie Sbrocchi, Shayne Taback, Raja Padidela, Nick J. Shaw, Eva Hosszu, Mikhail Kostik, Ekaterina Alexeeva, Kebashni Thandrayen, Nazih Shenouda, Jacob L. Jaremko, Gangadhar Sunkara, Sarfaraz Sayyed, R. Paul Aftring, Craig F. Munns
Summary: In this study, children with GIO who received intravenous zoledronic acid (ZA) showed a significant increase in lumbar spine bone density z score (LSBMDZ) compared to those who received a placebo after 1 year of treatment. Most adverse events occurred after the first infusion.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Endocrinology & Metabolism
Kim Phung, Laura McAdam, Jinhui Ma, Hugh J. McMillan, Stefan Jackowski, Maya Scharke, Mary-Ann Matzinger, Nazih Shenouda, Khaldoun Koujok, Jacob L. Jaremko, Kevin Smit, Scott Walker, Colleen Hartigan, Nasrin Khan, Victor N. Konji, Lynn MacLeay, Marika Page, Elizabeth Sykes, Marie-Eve Robinson, Nathalie Alos, Elizabeth A. Cummings, Josephine Ho, Anne Marie Sbrocchi, Robert Stein, David Saleh, B. Catharine Craven, Utkarsh J. Dang, Kerry Siminoski, Frank Rauch, Leanne M. Ward
Summary: This study found that markers of systemic glucocorticoid exposure, such as shorter stature, greater bone age delay, and lower lumbar spine bone mineral density, were associated with spine fragility in patients with DMD.
OSTEOPOROSIS INTERNATIONAL
(2023)
Article
Cell Biology
Zhihai Cao, Yuan Xue, Jiaqian Wang
Summary: Osteoporosis is caused by decreased bone formation and increased bone absorption, with ferroptosis playing a key role. Ferroptosis may inhibit bone formation and promote bone absorption through oxidative stress, leading to osteoporosis.
Review
Pharmacology & Pharmacy
Shenglei Yang, Yuying Sun, Leonid Kapilevich, Xin'an Zhang, Yue Huang
Summary: Osteoporosis is a common skeletal disorder that primarily affects the elderly and postmenopausal women. Drug therapy is currently used as the main treatment, but long-term use can lead to drug resistance and side effects. Therefore, researchers are exploring natural plant compounds as an alternative. Curcumin, a natural phenolic compound, has shown potential as a candidate for treating osteoporosis due to its various pharmacological and biological activities. This review summarizes the mechanisms and therapeutic applications of curcumin in preventing and mitigating osteoporosis, providing valuable references for further research and development of curcumin.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Kangtao Jin, Lin Zheng, Lin Ye, Ziang Xie, Jiawei Gao, Chao Lou, Wenzheng Pan, Bin Pan, Shijie Liu, Zhenzhong Chen, Dengwei He
Summary: The study demonstrates that CSB6B suppresses osteoclast differentiation and bone resorption while enhancing osteoblast mineralization by inhibiting the NF-KB pathway and promoting Runx expression. In murine models, CSB6B has shown protective effects against pathological bone destruction and bone loss induced by estrogen deficiency. MIF inhibition by CSB6B could be a potential therapeutic approach for osteolytic bone disorders and osteoporosis.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Zeren Sun, Dengqiu Xu, Lei Zhao, Xihua Li, Sijia Li, Xiaofei Huang, Chunjie Li, Lixin Sun, Bing Liu, Zhenzhou Jiang, Luyong Zhang
Summary: The study found that fenofibrate can promote the differentiation of myofibers by down-regulating the expression of myostatin protein in myoblasts, significantly improving muscle function and reducing muscle damage in mdx mice, along with anti-inflammatory effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Clinical Neurology
Craig M. Zaidman, Crystal M. Proud, Craig M. Mcdonald, Kelly J. Lehman, Natalie L. Goedeker, Stefanie Mason, Alexander P. Murphy, Maitea Guridi, Shufang Wang, Carol Reid, Eddie Darton, Christoph Wandel, Sarah Lewis, Jyoti Malhotra, Danielle A. Griffin, Rachael A. Potter, Louise R. Rodino-Klapac, Jerry R. Mendell
Summary: The study ENDEAVOR demonstrated that the commercial process delandistrogene moxeparvovec is safe and effective in improving micro-dystrophin expression in patients with Duchenne muscular dystrophy. After 12 weeks of treatment, significant improvements were observed in micro-dystrophin expression, as well as patient's functional outcomes and quality of life at 1 year.
ANNALS OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chao Liu, Yining Li, Ren Sheng, Xiaowan Han, Li Bao, Chenyin Wang, Weizhi Wang, Xinhai Jiang, Jiangxue Han, Lijuan Lei, Ni Li, Jing Zhang, Minghua Chen, Yan Li, Yexiang Wu, Shunwang Li, Yu Ren, Yanni Xu, Shuyi Si
Summary: The study demonstrated that the N-methylpyridine-chlorofuranformamide analog 3i1 shows promise in upregulating OPG activity, inhibiting RANKL-induced osteoclastogenesis, and promoting osteoblast differentiation, potentially serving as a new therapeutic agent for osteoporosis.
BIOORGANIC CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Sophia Ogechi Ekeuku, Kok-Lun Pang, Kok-Yong Chih
Summary: Caffeic acid, a metabolite of hydroxycinnamate and phenylpropanoid, acts as an antioxidant to reduce osteoclastogenesis and bone resorption. However, in some cases, it may have no effect on bone resorption or even impair bone mechanical properties in normal rats.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Endocrinology & Metabolism
Kim Phung, Laura McAdam, Jinhui Ma, Hugh J. McMillan, Stefan Jackowski, Maya Scharke, Mary-Ann Matzinger, Nazih Shenouda, Khaldoun Koujok, Jacob L. Jaremko, Nagwa Wilson, Scott Walker, Colleen Hartigan, Nasrin Khan, Marika Page, Marie-Eve Robinson, David S. Saleh, Kevin Smit, Frank Rauch, Kerry Siminoski, Leanne M. Ward
Summary: This study investigated factors associated with incident vertebral fractures (VFs) in Duchenne muscular dystrophy patients. The results showed that spinal deformity index, non-fracture indicators, and bone age delay were all associated with incident VFs. Therefore, preventing first fractures is necessary in high-risk populations.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Engineering, Biomedical
Wei Zhang, Xingzhi Zhou, Weiduo Hou, Erman Chen, Chenyi Ye, Mo Chen, Qian Lu, Xiaohua Yu, Weixu Li
Summary: In this study, a molecular therapeutic strategy mediated by a SIRT-1 agonist was reported to reverse the imbalance in bone homeostasis by regulating osteogenesis and osteoclastogenesis simultaneously. The sustained release of SRT2104 from mineral coated acellular matrix microparticles effectively enhanced osteogenic differentiation and mineralization, while attenuating the formation and function of excessive osteoclasts by integrating multiple vital upstream signals. Animal models also demonstrated the accelerated healing and improved osseointegration of osteoporotic bone defects.
BIOACTIVE MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Ester De Leo, Anna Taranta, Roberto Raso, Elena Polishchuk, Valentina D'Oria, Marco Pezzullo, Bianca Maria Goffredo, Sara Cairoli, Francesco Bellomo, Giulia Battafarano, Francesca Diomedi Camassei, Andrea Del Fattore, Roman Polishchuk, Francesco Emma, Laura Rita Rega
Summary: Cysteamine is the only therapy for nephropathic cystinosis, but compliance to therapy is often weak. Genistein, found in soy, has been found to improve kidney injury caused by cystinosis and may represent a potential treatment.
HUMAN MOLECULAR GENETICS
(2023)
Article
Endocrinology & Metabolism
Maria Papageorgiou, Emmanuel Biver, Julie Mareschal, Nicholas Edward Phillips, Alexandra Hemmer, Emma Biolley, Nathalie Schwab, Emily N. C. Manoogian, Elena Gonzalez Rodriguez, Daniel Aeberli, Didier Hans, Caroline Pot, Satchidananda Panda, Nicolas Rodondi, Serge L. Ferrari, Tinh-Hai Collet
Summary: This study investigated the impact of time-restricted eating (TRE) versus standard dietary advice (SDA) on bone health. The results showed that TRE had no detrimental effects on bone health in the overall population, but in weight loss responders, it was associated with some bone-sparing effects compared with SDA.
Article
Biochemistry & Molecular Biology
Michela Rossi, Viviana De Martino, Laura Di Giuseppe, Giulia Battafarano, Jacopo Di Gregorio, Sara Terreri, Francesco Marampon, Salvatore Minisola, Andrea Del Fattore
Summary: The effects of the histone deacetylase inhibitor PXD-101 on human osteosarcoma cells were investigated. The study found that PXD-101 inhibited cell proliferation, induced apoptosis, and inhibited cell migration. This study suggests that PXD-101 may be a potential new therapeutic approach for osteosarcoma patients.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Endocrinology & Metabolism
Francesca Marini, Francesca Giusti, Elena Marasco, Luciano Xumerle, Katarzyna Malgorzata Kwiatkowska, Paolo Garagnani, Emmanuel Biver, Serge Ferrari, Giovanni Iolascon, Teresa Iantomasi, Maria Luisa Brandi
Summary: Atypical femur fractures (AFFs) are rare fractures that occur at the lateral cortex of the femur and are associated with rare genetic bone disorders and long-term use of antiresorption drugs. Genetic screening of unrelated patients with AFFs revealed a high frequency of rare variants in the SLC34A1 and SLC9A3R1 genes, suggesting a possible genetic risk factor for AFFs.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Michela Rossi, Andrea Del Fattore
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Rheumatology
Serge Ferrari, Bente Langdahl
Summary: Denosumab, a human monoclonal antibody against RANKL, inhibits osteoclast differentiation and activity, leading to anti-resorptive properties and anti-fracture efficacy. Compared with bisphosphonates, denosumab results in continuous bone mineral density gain during long-term treatment and rapid bone loss upon withdrawal. The underlying mechanisms for these effects are not fully understood, but emerging data suggest that denosumab may affect both osteoclasts and osteoblasts, causing sustained bone gain and bone loss. Future studies and clinical implications are discussed in this Perspective.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Medicine, General & Internal
Georgia Stimpson, Danielle Ramsey, Amy Wolfe, Anna Mayhew, Mariacristina Scoto, Giovanni Baranello, Robert Muni Lofra, Marion Main, Evelin Milev, Giorgia Coratti, Marika Pane, Valeria Sansone, Adele D'Amico, Enrico Bertini, Sonia Messina, Claudio Bruno, Emilio Albamonte, Elena Stacy Mazzone, Jacqueline Montes, Allan M. Glanzman, Zarazuela Zolkipli-Cunningham, Amy Pasternak, Tina Duong, Sally Dunaway Young, Matthew Civitello, Chiara Marini-Bettolo, John W. Day, Basil T. Darras, Darryl C. De Vivo, Richard S. Finkel, Eugenio Mercuri, Francesco Muntoni
Summary: The study investigates the motor function of participants with Spinal Muscular Atrophy (SMA) using the Revised Hammersmith Scale (RHS), and contextualizes the findings with the Hammersmith Functional Motor Scale-Expanded (HFMSE). The transitional group, including crawlers, standers, and walkers-with-assistance, shows the most significant decline in the RHS score over a year. The study highlights the importance of considering SMA type, motor function, and baseline RHS score in interpreting the change scores.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Pediatrics
Claudia Brogna, Marika Pane, Giorgia Coratti, Adele D'Amico, Elena Pegoraro, Luca Bello, Valeria Ada Maria Sansone, Emilio Albamonte, Sonia Messina, Antonella Pini, Maria Grazia D'Angelo, Claudio Bruno, Tiziana Mongini, Federica Silvia Ricci, Angela Berardinelli, Roberta Battini, Riccardo Masson, Enrico Silvio Bertini, Luisa Politano, Eugenio Mercuri
Summary: This study evaluated the impact of exon skipping mutations in DMD patients, finding that PUL 2.0 can detect changes in upper limb function. Patients amenable to skipping exon 44 had smaller changes, while those amenable to skipping exon 53 had larger changes. These findings are helpful in designing clinical trials and interpreting real-world data in non-ambulant patients.
Article
Endocrinology & Metabolism
J. A. Kanis, H. Johansson, E. McCloskey, E. Liu, K. E. Akesson, F. A. Anderson, R. Azagra, C. L. Bager, C. Beaudart, H. A. Bischoff-Ferrari, E. Biver, O. Bruyere, J. A. Cauley, J. R. Center, R. Chapurlat, C. Christiansen, C. Cooper, C. J. Crandall, S. R. Cummings, J. A. P. da Silva, B. Dawson-Hughes, A. Diez-Perez, A. B. Dufour, J. A. Eisman, P. J. M. Elders, S. Ferrari, Y. Fujita, S. Fujiwara, C. -c. Glueer, I. Goldshtein, D. Goltzman, V. Gudnason, J. Hall, D. Hans, M. Hoff, R. J. Hollick, M. Huisman, M. Iki, S. Ish-Shalom, G. Jones, M. K. Karlsson, S. Khosla, D. P. Kiel, W. -p. Koh, F. Koromani, M. A. Kotowicz, H. Kroger, T. Kwok, O. Lamy, A. Langhammer, B. Larijani, K. Lippuner, D. Mellstrom, T. Merlijn, A. Nordstrom, P. Nordstrom, T. W. O'Neill, B. Obermayer-Pietsch, C. Ohlsson, E. S. Orwoll, J. A. Pasco, F. Rivadeneira, A. -M. Schott, E. J. Shiroma, K. Siggeirsdottir, E. M. Simonsick, E. Sornay-Rendu, R. Sund, K. M. A. Swart, P. Szulc, J. Tamaki, D. J. Torgerson, N. M. van Schoor, T. P. van Staa, J. Vila, N. J. Wareham, N. C. Wright, N. Yoshimura, M. C. Zillikens, M. Zwart, L. Vandenput, N. C. Harvey, M. Lorentzon, W. D. Leslie
Summary: A large international meta-analysis finds that a previous history of fracture is associated with an increased risk of future fractures, regardless of age, sex, and bone mineral density. The study highlights the importance of considering previous fracture history as a risk factor for fracture prevention strategies.
OSTEOPOROSIS INTERNATIONAL
(2023)
Article
Rheumatology
Marco Gattorno, Laura Obici, Inmaculada Calvo Penades, Tilmann Kallinich, Susanne Benseler, Elise Dekker, Jeremy Levy, Fabrizio De Benedetti, Helen Lachmann
Summary: This study assessed the efficacy, safety, and tolerability of canakinumab in TRAPS patients during a 72-week long-term, open-label extension. The results showed that long-term canakinumab treatment effectively controlled disease activity and reduced flare incidence in TRAPS patients. No new safety concerns were identified.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Rheumatology
Fabrizio De Benedetti, Alexei A. Grom, Paul A. Brogan, Claudia Bracaglia, Manuela Pardeo, Giulia Marucci, Despina Eleftheriou, Charalampia Papadopoulou, Grant S. Schulert, Pierre Quartier, Jordi Anton, Christian Laveille, Rikke Frederiksen, Veronica Asnaghi, Maria Ballabio, Philippe Jacqmin, Cristina de Min
Summary: The objective of this study was to confirm the adequacy of an emapalumab dosing regimen in relation to interferon-γ (IFN-γ) activity and assess its efficacy and safety in treating MAS secondary to sJIA or AOSD. The results showed that emapalumab was efficacious in inducing remission of MAS and viral infections were observed.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Cell & Tissue Engineering
Sharon Russo, Federica Scotto di Carlo, Antonio Maurizi, Giorgio Fortunato, Anna Teti, Danilo Licastro, Carmine Settembre, Tommaso Mello, Fernando Gianfrancesco
Summary: This study describes the establishment of a Zfp687 knock-in mouse model that recapitulates the Paget's disease (PDB) phenotype, leading to significantly altered bone remodeling. The mutation is associated with osteolytic phase, disrupted osteoblast activity, and the presence of woven bone, consistent with the PDB phenotype. Moreover, the study also reveals a link between osteoarthritis and PDB in this mouse model and highlights the oncogenic potential of ZNF687.
Article
Neurosciences
Vito Luigi Colona, Enrico Bertini, Maria Cristina Digilio, Adele D'Amico, Antonio Novelli, Stefano Pro, Elisa Pisaneschi, Francesco Nicita
Summary: POLR3B gene encodes the RPC2 subunit of RNA polymerase III, and pathogenic variants are associated with various disorders, including hypomyelinating leukodystrophy and Charcot-Marie-Tooth syndrome type 1I. In this study, a new variant in the POLR3B gene was identified in a patient with developmental delay, epilepsy, and polyneuropathy.
Article
Genetics & Heredity
Aurelien Perrin, Corinne Metay, Marco Savarese, Rabah Ben Yaou, German Demidov, Isabelle Nelson, Guilhem Sole, Yann Pereon, Enrico Silvio Bertini, Fabiana Fattori, Adele D'Amico, Federica Ricci, Mira Ginsberg, Andreea Seferian, Odile Boespflug-Tanguy, Laurent Servais, Francoise Chapon, Emmeline Lagrange, Karen Gaudon, Adrien Bloch, Robin Ghanem, Lucie Guyant-Marechal, Mridul Johari, Charles Van Goethem, Michel Fardeau, Raul Juntas Morales, Casie A. Genetti, Minttu Marttila, Michel Koenig, Alan Beggs, Bjarne Udd, Gisele Bonne, Mireille Cossee
Summary: Titinopathies are complex neuromuscular pathologies caused by mutations in the titin gene (TTN). A study identified multiple deletion-type CNVs in the TTN gene in several families, revealing new genotype-phenotype associations, mainly distal myopathy.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Endocrinology & Metabolism
Alfredo Cappariello, Maurizio Muraca, Anna Teti, Nadia Rucci
Summary: Extracellular vesicles (EVs) are potential biomarkers for the diagnosis and monitoring of osteoporosis. They contain molecular cargos involved in bone metabolism and have distinct molecular profiles in different types of osteoporosis. Circulating EVs could be used to identify new biomarkers and diagnose osteoporosis in liquid biopsies.
CALCIFIED TISSUE INTERNATIONAL
(2023)