Article
Multidisciplinary Sciences
Kai Dai, Qinghao Zhang, Shunshu Deng, Yuanman Yu, Fuwei Zhu, Shuang Zhang, YuanZhong Pan, Dandan Long, Jing Wang, Changsheng Liu
Summary: Constructing in vivo osteo-organoids by implanting bone morphogenetic protein-2-loaded scaffolds into the internal muscle pocket near the femur of mice supports the growth and subsequent harvest of therapeutically useful cells, and these cells demonstrate therapeutic potentials in cell therapies such as mitigating chronic liver fibrosis and reconstituting impaired immune organs.
Article
Cell Biology
Annamaria Aprile, Laura Raggi, Simona Bolamperti, Isabella Villa, Mariangela Storto, Gaia Morello, Sarah Marktel, Claudio Tripodo, Maria Domenica Cappellini, Irene Motta, Alessandro Rubinacci, Giuliana Ferrari
Summary: Clinical evidence suggests a relationship between blood and bone, but the underlying mechanism is not fully understood. A study using beta-thalassemia as a model found that increased fibroblast growth factor 23 (FGF23) levels in patients and mice with beta-thalassemia were induced by erythropoietin via ERK1/2 and STAT5 pathways. Inhibiting FGF23 signaling with carboxyl-terminal FGF23 peptide rescued bone defects and restored hematopoietic stem cell function in mice with beta-thalassemia. FGF23 may serve as a molecular link connecting anemia, bone, and the hematopoietic stem cell niche.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Annamaria Aprile, Laura Raggi, Simona Bolamperti, Isabella Villa, Mariangela Storto, Gaia Morello, Sarah Marktel, Claudio Tripodo, Maria Domenica Cappellini, Irene Motta, Alessandro Rubinacci, Giuliana Ferrari
Summary: This study demonstrates the overproduction of fibroblast growth factor 23 (FGF23) in patients and mice with beta-thalassemia, and shows that inhibition of FGF23 signaling is a safe and effective therapeutic strategy to rescue bone defects and restore hematopoietic stem cell function. FGF23 may serve as a molecular link connecting anemia, bone, and the HSC niche.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Tiago C. Luis, Nikolaos Barkas, Joana Carrelha, Alice Giustacchini, Stefania Mazzi, Ruggiero Norfo, Bishan Wu, Affaf Aliouat, Jose A. Guerrero, Alba Rodriguez-Meira, Tiphaine Bouriez-Jones, Iain C. Macaulay, Maria Jasztal, Guangheng Zhu, Heyu Ni, Matthew J. Robson, Randy D. Blakely, Adam J. Mead, Claus Nerlov, Cedric Ghevaert, Sten Eirik W. Jacobsen
Summary: In this study, the researchers uncover a feedback mechanism in which IL-1 secreted by activated platelets signals through niche Lepr+ cells to activate HSCs and restore platelet homeostasis.
NATURE COMMUNICATIONS
(2023)
Review
Cell Biology
Julia Froebel, Theresa Landspersky, Guelce Percin, Christina Schreck, Susann Rahmig, Alessandro Ori, Daniel Nowak, Marieke Essers, Claudia Waskow, Robert A. J. Oostendorp
Summary: The bone marrow environment, known as the niche, plays a vital role in maintaining blood cell formation throughout life. Different types of stress can disrupt the niche, leading to deregulation of hematopoietic stem cells and their function. Both acute and chronic insults can alter the cellular composition and structure of the niche, ultimately affecting hematopoiesis and increasing susceptibility to diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Cornelia Lee-Thedieck, Peter Schertl, Gerd Klein
Summary: This review provides a comprehensive overview of the extracellular matrix (ECM) in hematopoietic stem cell (HSC) niches and highlights its importance in regulating cellular function and niche structure. The role of different classes of ECM molecules and their interactions with cells are discussed, along with the significance of matrix remodeling and biophysics in HSC niche function. The review also examines the application of current knowledge of ECM in artificial HSC niches for HSC expansion, targeted differentiation, and drug testing.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Review
Immunology
Francesca Matteini, Medhanie A. Mulaw, M. Carolina Florian
Summary: The aging of the bone marrow niche leads to declining HSC function, but certain niche structures and signals are crucial for maintaining HSC function. The use of new technical tools has revealed the impact of BM niche aging on HSCs.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Chemistry, Physical
Ada Congrains, Juares Bianco, Renata G. Rosa, Rubia I. Mancuso, Sara T. O. Saad
Summary: HSC depend on signals from specialized niches for production, 2D models may hinder clinical application, and recreating bone marrow complexity may offer new therapeutic avenues.
Article
Hematology
Kyomi J. Igarashi, Iwo Kucinski, Yan Yi Chan, Tze-Kai Tan, Hwei Minn Khoo, David Kealy, Joydeep Bhadury, Ian Hsu, Pui Yan Ho, Kouta Niizuma, John W. Hickey, Garry P. Nolan, Katherine S. Bridge, Agnieszka Czechowicz, Berthold Gottgens, Hiromitsu Nakauchi, Adam C. Wilkinson
Summary: Hematopoietic stem cells (HSCs) are rare cells that can regenerate the blood and immune system. Allogeneic HSC transplantation (HSCT) is a curative therapy for hematolymphoid diseases, but it carries risks. This study demonstrates that using physioxic culture conditions can improve the selectivity of polyvinyl alcohol (PVA)-based HSC cultures. They also show that HSC-selective ex vivo cultures can remove GVHD-causing T cells and can be combined with genotoxic-free antibody-based conditioning HSCT approaches.
Article
Chemistry, Physical
Ya-Ting Hsu, Li-Hsien Chen, Ya-Hui Liu, Shih-Kai Chu, Tsai-Yun Chen, Kuen-Jer Tsai, Meng-Ru Shen, Wentai Liu
Summary: This study demonstrates that electrical sympathetic neuromodulation (ESN) of the bone marrow can protect it from chemotherapy-induced injury and promote hematopoietic regeneration. ESN can mediate the production of several hematopoietic stem cell maintenance factors, reduce the release of pro-inflammatory cytokines, and reduce the severity of chemotherapy-related leukopenia, thrombocytopenia, and mortality.
Review
Immunology
Yoshiki Omatsu
Summary: Throughout adult life, most blood cells including immune cells are produced from hematopoietic stem cells (HSCs) in the bone marrow. The niche for HSCs has been a subject of debate, but accumulated studies suggest that a specific population of fibroblastic reticular cells, called CAR/LepR(+) cells, are essential for maintaining HSCs and lymphoid progenitors.
INFLAMMATION AND REGENERATION
(2023)
Article
Multidisciplinary Sciences
Sarah Ennis, Alessandra Conforte, Eimear O'Reilly, Javid Sabour Takanlu, Tatiana Cichocka, Sukhraj Pal Dhami, Pamela Nicholson, Philippe Krebs, Pilib O. Broin, Eva Szegezdi
Summary: In this study, a single-cell gene expression database of 339,381 bone marrow cells was established to comprehensively characterize the microenvironment of both healthy and acute myeloid leukemia (AML). Significant changes in cell type proportions and gene expression were observed in AML, indicating disruption of the entire niche. Predicted interactions between hematopoietic stem and progenitor cells (HSPCs) and other bone marrow cell types were also explored, revealing an expansion of interactions in AML that promote HSPC-cell adhesion, immunosuppression, and cytokine signaling. Transforming growth factor b1 (TGFB1)-related interactions were particularly widespread and were shown to drive AML cell quiescence in vitro. These findings highlight potential mechanisms of enhanced AML-HSPC competitiveness and a skewed microenvironment fostering AML growth.
Article
Multidisciplinary Sciences
Runfeng Miao, Harim Chun, Xing Feng, Ana Cordeiro Gomes, Jungmin Choi, Joao P. Pereira
Summary: This study reveals that a complex homeostatic balance between hematopoietic stem cells (HSCs) and hematopoietic progenitor cells is maintained through competition for a limited amount of cell signaling molecule. When early hematopoietic progenitors fail to interact with specific cells, HSC numbers increase.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Juo-Chin Yao, Karolyn A. Oetjen, Tianjiao Wang, Haoliang Xu, Grazia Abou-Ezzi, Joseph R. Krambs, Salil Uttarwar, Eric J. Duncavage, Daniel C. Link
Summary: Myeloproliferative neoplasms (MPNs) are associated with changes in the bone marrow microenvironment, and disrupting TGF-beta signaling in bone marrow mesenchymal stromal cells can prevent the development of myelofibrosis. However, it does not rescue the defective hematopoietic niche induced by MPNs.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Engineering, Biomedical
Chandralekha Chatterjee, Peter Schertl, Miriam Frommer, Anita Ludwig-Husemann, Anna Mohra, Nadine Dilger, Toufik Naolou, Sophia Meermeyer, Timna Claire Bergmann, Alejandro Alonso Calleja, Cornelia Lee-Thedieck
Summary: Artificial niches play a crucial role in regenerative medicine research, providing insights into the biophysical and biochemical processes of hematopoietic stem cells, as well as facilitating HSCs expansion and targeted differentiation. Due to the lack of natural microenvironment, biomaterials are essential in recreating niche environments, offering promising applications in various fields.
ACTA BIOMATERIALIA
(2021)
Article
Endocrinology & Metabolism
Tilman D. Rachner, Cornelia S. Link-Rachner, Martin Bornhaeuser, Lorenz C. Hofbauer
Summary: Patients who undergo allogeneic hematopoietic cell transplantation (HCT) are at an increased risk of developing bone loss due to various factors, including the disease itself and the applied therapies. This review provides an overview of the underlying mechanisms and offers screening and treatment recommendations for managing this complication.
Article
Endocrinology & Metabolism
Ralf Oheim, Elena Tsourdi, Lothar Seefried, Gisela Beller, Max Schubach, Eik Vettorazzi, Julian Sturznickel, Tim Rolvien, Nadja Ehmke, Alena Delsmann, Franca Genest, Ulrike Krueger, Tomasz Zemojtel, Florian Barvencik, Thorsten Schinke, Franz Jakob, Lorenz C. Hofbauer, Stefan Mundlos, Uwe Kornak
Summary: The impact of genetic testing on the differential diagnosis of adult LBMD was investigated in this study. Clinical criteria for predicting monogenic forms were also defined. The results showed that genetic testing can easily distinguish overlapping spectra of monogenic adult LBMD, and the proposed clinical criteria can help maximize the diagnostic yield.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Endocrinology & Metabolism
Lorenz C. Hofbauer, Bjoern Busse, Richard Eastell, Serge Ferrari, Morten Frost, Ralph Mueller, Andrea M. Burden, Fernando Rivadeneira, Nicola Napoli, Martina Rauner
Summary: Increased fracture risk is a serious complication of diabetes, leading to prolonged immobility and hospitalizations that can result in significant morbidity and mortality. In type 1 diabetes, bone mass and strength are reduced, leading to a five-fold increased risk of lifelong fractures. In type 2 diabetes, fracture risk is increased despite normal bone mass. The fragility of bones in diabetes can be attributed to cellular abnormalities, matrix interactions, immune and vascular changes, and musculoskeletal maladaptation to chronic hyperglycemia.
LANCET DIABETES & ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Aliya A. Khan, Mishaela R. Rubin, Peter Schwarz, Tamara Vokes, Dolores M. Shoback, Claudia Gagnon, Andrea Palermo, Claudio Marcocci, Bart L. Clarke, Lisa G. Abbott, Lorenz C. Hofbauer, Lynn Kohlmeier, Susanne Pihl, Xuebei An, Walter Frank Eng, Alden R. Smith, Jenny Ukena, Christopher T. Sibley, Aimee D. Shu, Lars Rejnmark
Summary: TransCon PTH demonstrated efficacy in maintaining normocalcemia and allowing independence from conventional therapy in individuals with hypoparathyroidism. The treatment also showed significant improvements in health-related quality of life and hypoparathyroidism-related symptoms.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Endocrinology & Metabolism
Eva Maria Woelfel, Franziska Lademann, Haniyeh Hemmatian, Stephane Blouin, Phaedra Messmer, Lorenz C. Hofbauer, Bjoern Busse, Martina Rauner, Katharina Jaehn-Rickert, Elena Tsourdi
Summary: Hyperthyroidism causes secondary osteoporosis by promoting bone resorption. Osteocytic osteolysis and elevated tartrate-resistant acid phosphatase (TRAP) activity were observed in hyperthyroid mice. The bone microarchitecture and turnover recovered after treatment, but the osteocytic osteolysis effects were not reversed.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Review
Medicine, General & Internal
Elena Tsourdi, Athanasios D. Anastasilakis, Lorenz C. Hofbauer, Martina Rauner, Franziska Lademann
Summary: Irisin is a hormone-like myokine produced by skeletal muscle during exercise. It plays a role in the browning process, thermogenesis, and regulates the functions of osteoblasts, osteoclasts, and osteocytes. Recent studies have shown that serum irisin levels decrease with age and in conditions involving bone diseases. However, the validity and reproducibility of current methods of irisin measurement are under question.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biology
Nikolai P. Jaschke, Sophie Paehlig, Anupam Sinha, Timon E. Adolph, Maria Ledesma Colunga, Maura Hofmann, Andrew Wang, Sylvia Thiele, Julian Schwaerzler, Alexander Kleymann, Marc Gentzel, Herbert Tilg, Ben Wielockx, Lorenz C. Hofbauer, Martina Rauner, Andy Goebel, Tilman D. Rachner
Summary: This study reveals the cell-autonomous function of Dickkopf1 (DKK1) in controlling inflammatory responses and maintaining the elevated inflammatory tone of cancer cells. It is found that genetic DKK1 variants are linked to elevated cytokine production in healthy populations, and genetic deletion of DKK1 can ameliorate inflammation and disease trajectories in a mouse model.
COMMUNICATIONS BIOLOGY
(2022)
Article
Engineering, Biomedical
Sofie Dragoun Kolibova, Eva Maria Woelfel, Haniyeh Hemmatian, Petar Milovanovic, Herbert Mushumba, Birgit Wulff, Maximilian Neidhardt, Klaus Pueschel, Antonio Virgilio Failla, Annegreet Vlug, Alexander Schlaefer, Benjamin Ondruschka, Michael Amling, Lorenz C. Hofbauer, Martina Rauner, Bjoern Busse, Katharina Jaehn-Rickert
Summary: Type 1 diabetes mellitus (T1DM) is associated with increased bone fragility. Our study found accelerated osteocyte apoptosis and local mineralization in T1DM patients, suggesting that T1DM speeds up bone aging and impairs its biomechanical competence. Dysfunction of the osteocyte network hampers bone remodeling and repair, contributing to the increased fracture risk in T1DM individuals.
ACTA BIOMATERIALIA
(2023)
Article
Endocrinology & Metabolism
Manuel Gado, Annett Heinrich, Denise Wiedersich, Katrin Sameith, Andreas Dahl, Vasileia I. Alexaki, Michael M. Swarbrick, Ulrike Baschant, Ingo Grafe, Nikolaos Perakakis, Stefan R. Bornstein, Martina Rauner, Lorenz C. Hofbauer, Holger Henneicke
Summary: This study demonstrates that activation of the sympathetic nervous system through cold exposure or selective I33-adrenergic receptor agonist can alleviate the adverse metabolic effects caused by chronic glucocorticoid exposure. Cold exposure preserves the function of brown adipose tissue and reverses white adipose tissue lipid accumulation, correcting obesity, hyperinsulinemia, and hyperglycemia caused by glucocorticoids.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Engineering, Biomedical
Gloria Ruiz-Gomez, Juliane Salbach-Hirsch, Jan-Niklas Duerig, Linda Koehler, Kanagasabai Balamurugan, Sandra Rother, Sophie-Luise Heidig, Stephanie Moeller, Matthias Schnabelrauch, Giulia Furesi, Sophie Paehlig, Pedro M. Guillem-Gloria, Christine Hofbauer, Vera Hintze, M. Teresa Pisabarro, Joerg Rademann, Lorenz C. Hofbauer
Summary: The WNT signaling pathway is important for bone development and regeneration, and abnormalities in WNT ligands and inhibitors are associated with various bone diseases. This study focused on glycosaminoglycan (GAG) recognition by DKK1, a WNT inhibitor, and aimed to develop WNT signaling regulators. Through a multidisciplinary approach, researchers designed and synthesized GAG derivatives with improved neutralizing properties for DKK1. These derivatives showed increased WNT pathway activity and improved bone regeneration in experimental models. The findings suggest that rationally engineered GAG variants could be used as novel therapeutic approaches.
Article
Biochemistry & Molecular Biology
Maria G. Ledesma-Colunga, Ulrike Baschant, Heike Weidner, Tiago C. Alves, Peter Mirtschink, Lorenz C. Hofbauer, Martina Rauner
Summary: In this study, the authors investigated the role of transferrin receptor 2 (Tfr2) in the pathogenesis of inflammatory arthritis. They found that Tfr2-deficient mice developed more severe joint inflammation and bone erosion compared to control mice. Further experiments suggested that Tfr2 deficiency promoted macrophage polarization towards a pro-inflammatory state, contributing to the progression of arthritis.
Article
Endocrinology & Metabolism
Souad Daamouch, Sylvia Thiele, Lorenz Hofbauer, Martina Rauner
Summary: The link between obesity and low bone strength is a significant medical concern. Previous research has shown that Dkk1, a Wnt inhibitor, is upregulated in bone tissue in obesity and drives obesity-induced bone loss. This study investigated the role of adipogenic Dkk1 in bone homeostasis and obesity-induced bone loss in mice. The results suggest that adipogenic Dkk1 plays a transient role in bone mass regulation during adolescence, but does not contribute to bone homeostasis or obesity-induced bone loss later in life.
ENDOCRINE CONNECTIONS
(2023)
Article
Medicine, General & Internal
Athanasios D. Anastasilakis, Stergios A. Polyzos, Panagiotis A. Vorkas, Athina Gkiomisi, Maria P. Yavropoulou, Martina Rauner, Panagiotis Nikolakopoulos, Stergios Papachatzopoulos, Polyzois Makras, Spyridon Gerou, Lorenz C. Hofbauer, Andrea Palermo, Elena Tsourdi
Summary: Menstrual cessation affects lipid metabolism. This study evaluated the effects of goserelin-induced menstrual cessation and subsequent menstrual restoration on lipid metabolism. The results showed that levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein A1 increased during menstrual cessation, but remained unchanged during menstrual restoration.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Mahdi Jaber, Lorenz C. Hofbauer, Christine Hofbauer, Georg N. Duda, Sara Checa
Summary: Bone regeneration is impaired in type 2 diabetes mellitus (T2DM), with alterations in MSC proliferation, migration, and osteoblast differentiation playing a significant role. Mechanical changes have minimal impact on reduced bone regeneration in T2DM. These findings have clinical implications for the treatment of bone fractures in patients with T2DM.
Article
Medicine, Research & Experimental
Lorenz C. Hofbauer, Franziska Lademann, Martina Rauner
Summary: Osteocytes, senescent cells implicated in bone loss disorders, have been shown to be effectively cleared through systemic senolysis, preventing age-related bone loss and mitigating bone marrow adiposity. Cell-specific senolysis in osteocytes alone had only a partial effect. Surprisingly, transplantation of senescent fibroblasts into young mice led to osteocyte senescence and bone loss. These findings on osteocyte senescence and the effects of remote senolysis suggest potential strategies against multisystem aging.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
