Article
Endocrinology & Metabolism
Jan Willem Bek, Chen Shochat, Adelbert De Clercq, Hanna De Saffel, Annekatrien Boel, Juriaan Metz, Frans Rodenburg, David Karasik, Andy Willaert, Paul J. Coucke
Summary: By utilizing crispant screening in zebrafish, researchers were able to effectively validate the functional roles of osteoporosis candidate genes, demonstrating a promising approach for rapid functional screening in this field.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Article
Endocrinology & Metabolism
Maria L. Mace, Eva Gravesen, Anders Nordholm, Soeren Egstrand, Marya Morevati, Carsten Nielsen, Andreas Kjaer, Geert Behets, Patrick D'Haese, Klaus Olgaard, Ewa Lewin
Summary: Research suggests an association between lower bone mineral density and vascular calcification, with chronic kidney disease affecting mineral balance and bone turnover. The study demonstrates that the presence of vascular calcification leads to lower bone mineral density, impairs bone metabolism, and indicates a communication pathway between vasculature and bone tissue.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Review
Endocrinology & Metabolism
Alice Costantini, Riikka E. Makitie, Markus A. Hartmann, Nadja Fratzl-Zelman, M. Carola Zillikens, Uwe Kornak, Kent Soe, Outi Makitie
Summary: Early-onset osteoporosis (EOOP) is a disease that affects children, premenopausal women, and men aged <50 years. It may be caused by various factors such as chronic illness, medication, and nutritional deficiencies. Genetic variants in key genes play a crucial role in the pathogenesis of EOOP. The diagnosis and genetic diagnosis of EOOP are complex and require comprehensive assessments. Rare monogenic forms of EOOP are mainly associated with gene defects in the WNT pathway.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Endocrinology & Metabolism
Frank C. Ko, Margaret M. Kobelski, Wanlin Zhang, Gina M. Grenga, Janaina S. Martins, Marie B. Demay
Summary: Phosphate restriction leads to decreased bone formation and increased bone marrow adipose tissue by affecting cellular signaling pathways and gene expression.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Article
Endocrinology & Metabolism
Erik F. Eriksen, Roland Chapurlat, Rogely Waite Boyce, Yifei Shi, Jacques P. Brown, Stephane Horlait, Donald Betah, Cesar Libanati, Pascale Chavassieux
Summary: The bone-forming agent romosozumab significantly increases modeling-based bone formation on cancellous and endocortical surfaces in the first 2 months of treatment, but not on periosteal surfaces. There was no significant difference in remodeling-based bone formation on all three bone surfaces after 2 months of romosozumab treatment.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Endocrinology & Metabolism
Lisa Y. Lawson, Michael D. Brodt, Nicole Migotsky, Christopher J. Chermside-Scabbo, Ramya Palaniappan, Matthew J. Silva
Summary: The secretion of Wnt ligands is essential for adult bone homeostasis, and inhibiting their secretion results in decreased bone formation and increased resorption. Additionally, osteoblast-derived Wnts play a crucial role in mediating the bone anabolic response to tibial loading.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Endocrinology & Metabolism
Jonathan J. Rios, Kristin Denton, Jamie Russell, Julia Kozlitina, Carlos R. Ferreira, Amy F. Lewanda, Joshua E. Mayfield, Eva Moresco, Sara Ludwig, Miao Tang, Xiaohong Li, Stephen Lyon, Anas Khanshour, Nandina Paria, Aysha Khalid, Yang Li, Xudong Xie, Jian Q. Feng, Qian Xu, Yongbo Lu, Robert E. Hammer, Carol A. Wise, Bruce Beutler
Summary: Proper skeletal development requires coordination of complex molecular mechanisms, and disruption of these processes through genetic mutation can lead to skeletal abnormalities. The study successfully developed a high-throughput skeletal screening approach to identify genes essential for skeletal development, showing the feasibility of in vivo mutagenesis to create mouse models of skeletal disease and characterize mutations in developmentally essential genes like FAM20B. Results and engineered mouse models from the study are publicly available through the Mutagenetix database.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Article
Endocrinology & Metabolism
Annelies De Mare, Britt Opdebeeck, Ellen Neven, Patrick C. D'Haese, Anja Verhulst
Summary: Sclerostin, a negative regulator of the Wnt/β-catenin signaling pathway, inhibits bone formation and turnover. Depletion or deactivation of sclerostin promotes the development of ectopic calcification, with vascular smooth muscle cells undergoing dedifferentiation playing a central role.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Francois Robin, Daniel Chappard, Patricia Leroyer, Chloe Latour, Guillaume Mabilleau, Valerie Monbet, Thibault Cavey, Mathieu Horeau, Frederic Derbre, Marie-Paule Roth, Martine Ropert, Pascal Guggenbuhl, Olivier Loreal
Summary: This study investigates the respective roles of iron excess and hepcidin in the development of iron-related osteoporosis. The findings suggest that iron overload alone is not sufficient to induce osteoporosis, and low levels of hepcidin also contribute to its development.
Article
Endocrinology & Metabolism
Tori Kroon, Neharika Bhadouria, Paul Niziolek, Daniel Edwards, Roy Choi, Erica L. Clinkenbeard, Alexander Robling, Nilsson Holguin
Summary: Intervertebral disc degeneration, a leading cause of low back pain, lacks pharmacological treatment options. This study demonstrated that neutralization of sclerostin and/or dkk1 could stimulate Wnt signaling and enhance intervertebral disc structure in mice. The findings suggest that anti-sclerostin antibody may contribute to the restoration of intervertebral disc health.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Endocrinology & Metabolism
Yuka Kinoshita, Fatma F. Mohamed, Flavia Amadeu de Oliveira, Sonoko Narisawa, Koichi Miyake, Brian L. Foster, Jose Luis Millan
Summary: Hypophosphatasia (HPP) is a disease caused by loss-of-function mutations in the ALPL gene encoding tissue-nonspecific alkaline phosphatase (TNAP). Currently, enzyme replacement therapy (ERT) and gene therapy are the main methods for treating the disease. Gene therapy may be a promising alternative treatment that can significantly extend patient lifespan and improve their skeletal and dental conditions.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Article
Endocrinology & Metabolism
Xin Qin, Qing Jiang, Hisato Komori, Chiharu Sakane, Ryo Fukuyama, Yuki Matsuo, Kosei Ito, Toshihiro Miyazaki, Toshihisa Komori
Summary: The study revealed the crucial role of Runx2 in the expression of major bone matrix protein genes and Tnfsf11 after commitment into osteoblasts in mice, and its deficiency may lead to dwarfism and reduced bone mass in mice.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Article
Endocrinology & Metabolism
Wenzheng Wang, Tala Azar, Wei-Ju Tseng, Shaopeng Pei, Yilu Zhou, Xi Jiang, Nathaniel Dyment, X. Sherry Liu
Summary: This study investigated the temporal response of newly formed bone tissue and preexisting bone tissue to withdrawal from intermittent parathyroid hormone (PTH) treatment in an ovariectomized rat model. The results showed that modeling-based bone formation (MBF) sites had a greater contribution to the extended anabolic effect upon early withdrawal from PTH compared to remodeling-based bone formation (RBF) sites. Furthermore, newly formed bone tissue from MBF had greater resistance to PTH discontinuation-induced bone loss than those from RBF and preexisting bone.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Endocrinology & Metabolism
Mariah Farrell, Heather Fairfield, Samantha Costa, Anastasia D'Amico, Carolyne Falank, Daniel J. Brooks, Michaela R. Reagan
Summary: Obesity is a risk factor for many cancers and can increase bone marrow adipose tissue (BMAT), which may contribute to cancer progression. Activation of PPAR-γ can lead to increased BMAT, while the use of Scl-Ab has been shown to reverse the effects and improve bone parameters in an animal model.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Article
Endocrinology & Metabolism
John Garcia, Spenser S. Smith, Sangita Karki, Hicham Drissi, Henry H. Hrdlicka, Daniel W. Youngstrom, Anne M. Delany
Summary: miR-433-3p is a negative regulator of bone formation through various key signaling pathways such as PTH, MAPK, Wnt, and endogenous glucocorticoids, targeting multiple genes including Crebl, Hsd11b1, and Rspo3 to inhibit osteoblast activity and Wnt signaling pathway, reducing bone mass. In in vivo experiments, inhibitors of miR-433-3p can increase trabecular bone volume in mice, indicating its negative regulatory role in bone formation.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Article
Genetics & Heredity
Silke Peeters, Arne Decramer, Stuart Alan Cain, Peter Houpt, Frederik Verstreken, Jan Noyez, Christophe Hermans, Werner Jacobs, Martin Lammens, Erik Fransen, Ajay Anand Kumar, Geert Vandeweyer, Bart Loeys, Wim Van Hul, Clair Baldock, Eveline Boudin, Geert Mortier
Summary: A rare FBN2 gene variant was identified in a family with CTS, and a significant increase in the frequency of rare and high-impact FBN2 variants was observed in patients with sporadic CTS, suggesting a potential role of FBN2 in the pathogenesis of CTS.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Endocrinology & Metabolism
Z. Belaya, O. Golounina, A. Nikitin, N. Tarbaeva, E. Pigarova, E. Mamedova, M. Vorontsova, I. Shafieva, I. Demina, W. Van Hul
Summary: A young male patient with clinical signs of dyskeratosis congenita presented with multiple bilateral low-traumatic hip fractures. Whole exome sequencing revealed a previously unreported mutation in the PARN gene. Treatment with zoledronic acid was effective at preventing further fractures.
OSTEOPOROSIS INTERNATIONAL
(2021)
Article
Genetics & Heredity
Yentl Huybrechts, Eveline Boudin, Gretl Hendrickx, Ellen Steenackers, Neveen Hamdy, Geert Mortier, Guillermo Martinez Diaz-Guerra, Milagros Sierra Bracamonte, Natasha M. Appelman-Dijkstra, Wim Van Hul
Summary: Sclerosteosis is a high bone mass disorder caused by pathogenic variants in the genes encoding sclerostin or LRP4. This study demonstrates that a pathogenic variant in the first beta-propeller domain of LRP4 can contribute to the development of sclerosteosis.
Review
Immunology
Jonas De Kesel, Igor Fijalkowski, Justin Taylor, Panagiotis Ntziachristos
Summary: This article provides an overview of the emerging mechanisms of aberrant splicing, its contribution to oncogenesis, and its clinical potential in the treatment of blood cancers.
TRENDS IN IMMUNOLOGY
(2022)
Review
Endocrinology & Metabolism
Dylan J. M. Bergen, Antonio Maurizi, Melissa M. Formosa, Georgina L. K. McDonald, Ahmed El-Gazzar, Neelam Hassan, Maria-Luisa Brandi, Jose A. Riancho, Fernando Rivadeneira, Evangelia Ntzani, Emma L. Duncan, Celia L. Gregson, Douglas P. Kiel, M. Carola Zillikens, Luca Sangiorgi, Wolfgang Hogler, Ivan Duran, Outi Makitie, Wim Van Hul, Gretl Hendrickx
Summary: This article describes 59 high bone mass disorders and their underlying genetic causes, with a focus on the signaling pathways and mechanisms involved. The authors classify the known genes into subgroups based on a uniform Gene Ontology terminology, providing potential insights for experimental design and genetic screening. Additionally, the authors discuss the application of functional genomics in discovering new genes and mechanisms in high bone mass disorders, highlighting the importance of multidisciplinary collaborations and knowledge transfer from the laboratory to the clinic. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Genetics & Heredity
Tessi Beyltjens, Eveline Boudin, Nicole Revencu, Nele Boeckx, Miriam Bertrand, Leon Schuetz, Tobias B. Haack, Axel Weber, Eleni Biliouri, Mateja Vinksel, Anja Zagozen, Borut Peterlin, Shashidhar Pai, Aida Telegrafi, Lindsay B. Henderson, Courtney Ells, Lesley Turner, Wim Wuyts, Wim Van Hul, Gretl Hendrickx, Geert R. Mortier
Summary: By sequencing the genes, five pathogenic variants in CBFB were identified in a cohort of eight individuals with clinical and radiographic features reminiscent of CCD, confirming the previously suggested locus heterogeneity for CCD. CBFB-related CCD displayed similar dental and clavicular abnormalities as RUNX2-related CCD, while normal stature and neurocognitive problems were distinguishing features.
JOURNAL OF MEDICAL GENETICS
(2023)
Review
Genetics & Heredity
Evelien Van Dijck, Sigri Beckers, Sara Diels, Tammy Huybrechts, An Verrijken, Kim Van Hoorenbeeck, Stijn Verhulst, Guy Massa, Luc Van Gaal, Wim Van Hul
Summary: Recent research suggests that heterozygous PCSK1 variants may increase the risk of obesity. However, in this specific study, a rare variant was found to have no significant association with obesity. Furthermore, the role of PCSK1 variants in obesity remains inconclusive.
Article
Endocrinology & Metabolism
Gretl Hendrickx, Eveline Boudin, Ellen Steenackers, Corinne Collet, Geert R. Mortier, David Genevi, Wim Van Hul
Summary: CDD is a rare and severe bone dysplasia characterized by progressive sclerosis of the cranial and facial bones. In this study, two individuals from a consanguineous family with mild phenotypic features of CDD were investigated. Serum analysis revealed high levels of bone turnover markers, and exome sequencing identified a homozygous missense variant in the SP7 gene. Further studies are needed to understand the underlying mechanisms of how SP7 variants cause sclerosing bone dysplasia.
Article
Nutrition & Dietetics
Yentl Huybrechts, Pieter Evenepoel, Mathias Haarhaus, Etienne Cavalier, Geert Dams, Wim Van Hul, Patrick C. C. D'Haese, Anja Verhulst
Summary: This study investigates the association between renal osteodystrophy and bone turnover as well as the expression of osteocytic sclerostin. It also examines the effect of parathyroid hormone on sclerostin expression. The results show that sclerostin is regulated by parathyroid hormone, which in turn affects bone turnover and mineralization. Additionally, the study highlights the functional differences between trabecular and cortical bone, as the expression of osteocytic sclerostin depends on the respective bone compartment. Furthermore, circulating sclerostin has limited diagnostic performance, while changes in skeletal sclerostin expression occur more rapidly and prominently.
Article
Cell Biology
Lena Eismann, Igor Fijalkowski, Carla Veronica Galmozzi, Jiri Koubek, Frank Tippmann, Petra Van Damme, Guenter Kramer
Summary: This study reveals the role of SecB chaperone protein in co-translational translocation, showing that SecB primarily interacts with inner membrane proteins (IMPs) and other nascent cytoplasmic and translocated proteins, regulated by the chaperone trigger factor. The findings suggest an important function of SecB in protein maturation.
Article
Multidisciplinary Sciences
Qi Jin, Blanca Gutierrez Diaz, Tim Pieters, Yalu Zhou, Sonali Narang, Igor Fijalkwoski, Cristina Borin, Jolien Van Laere, Monique Payton, Byoung-Kyu Cho, Cuijuan Han, Limin Sun, Valentina Serafin, George Yacu, Wouter Von Loocke, Giuseppe Basso, Giulia Veltri, Ingrid Dreveny, Issam Ben-Sahra, Young Ah Goo, Stephanie L. Safgren, Yi-Chien Tsai, Beat Bornhauser, Praveen Kumar Suraneni, Alexandre Gaspar-Maia, Irawati Kandela, Pieter Van Vlierberghe, John D. Crispino, Aristotelis Tsirigos, Panagiotis Ntziachristos
Summary: This study reveals that in T cell acute lymphoblastic leukemia (T-ALL), ubiquitin-specific protease 11 (USP11) forms a complex with USP7 to deubiquitinate the oncogenic lymphocyte cell-specific protein-tyrosine kinase (LCK) and enhance its activity. Impairment of LCK activity leads to increased glucocorticoid receptor (GR) expression and glucocorticoids sensitivity. Additionally, the deubiquitinase activity plays a role in the transcriptional activation of GR target genes.
Article
Endocrinology & Metabolism
Yentl Huybrechts, Raphael De Ridder, Ellen Steenackers, Jean-Pierre Devogelaer, Geert Mortier, Gretl Hendrickx, Wim Van Hul
Summary: Paget's disease of bone (PDB) is a bone disorder caused by pathogenic variants in genes such as Sequestosome 1 (SQSTM1), PFN1, and ZNF687. In this study, coding regions of PFN1 and ZNF687 were screened in a Belgian PDB cohort, and rare non-synonymous coding variants were identified in ZNF687. The study supports the involvement of genetic variation in ZNF687 in classical PDB, expanding its mutational spectrum.
CALCIFIED TISSUE INTERNATIONAL
(2023)
Meeting Abstract
Endocrinology & Metabolism
Yentl Huybrechts, Raphael De Ridder, Bjorn De Samber, Eveline Boudin, Francesca Tonelli, Dries Knapen, Dorien Schepers, Jan De Beenhouwer, Jan Sijbers, Dylan Bergen, Chrissy Hammond, Antonella Forlino, Geert Mortier, Paul Coucke, P. Eckhard Witten, Ronald Kwon, Andy Willaert, Gretl Hendrickx, Wim Van Hul
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Genetics & Heredity
Ewa Hordyjewska-Kowalczyk, Wim Wuyts, Nele Boeckx, An Verdonck, Gretl Hendrickx, Geert Mortier
Summary: In this study, a 14-year-old boy with metaphyseal dysplasia with maxillary hypoplasia but without brachydactyly was described. Exome sequencing revealed a de novo heterozygous duplication within RUNX2, extending into the C-terminal activation domain.