Article
Cell Biology
Daisuke Tateiwa, Takashi Kaito, Kunihiko Hashimoto, Rintaro Okada, Joe Kodama, Junichi Kushioka, Zeynep Bal, Hiroyuki Tsukazaki, Shinichi Nakagawa, Yuichiro Ukon, Hiromasa Hirai, Hongying Tian, Ivan Alferiev, Michael Chorny, Satoru Otsuru, Seiji Okada, Masahiro Iwamoto
Summary: BMPs have been used clinically for bone formation in musculoskeletal disorders, but high doses can lead to adverse events. A potent antagonist of RAR gamma was found to enhance BMP-induced bone formation, leading to increased bone volume and thickness, as well as promoting chondrogenic gene expression. This suggests potential for improving BMP-2 based bone regeneration procedures in the future.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Cai-Ping Yan, Xing-Kuan Wang, Ke Jiang, Chong Yin, Chao Xiang, Yong Wang, Chaoyu Pu, Lu Chen, Yu-Ling Li
Summary: Bone defects are a global public health problem, and the available methods for inducing bone regeneration are limited. β-ecdysterone, a plant sterol similar to estrogen, has been found to promote bone regeneration by enhancing osteoblast differentiation and activating the BMP-2/Smad/Runx2/Osterix pathway. This study provides a new direction for osteogenic differentiation and offers novel therapeutic strategies for treating bone defects.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Kazuya Morita, Naoyuki Matsumoto, Kengo Saito, Toshihide Hamabe-Horiike, Keishi Mizuguchi, Yohei Shinmyo, Hiroshi Kawasaki
Summary: The study revealed that AQP4 is selectively expressed in astrocytes in the mouse cerebral cortex during development, and that BMP signaling plays a role in altering AQP4 levels in the cortex.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Junko Tachi, Takashi Onuma, Shinobu Yamaguchi, Woo Kim, Tomoyuki Hioki, Rie Matsushima-Nishiwaki, Kumiko Tanabe, Haruhiko Tokuda, Osamu Kozawa, Hiroki Iida
Summary: The study found that duloxetine suppresses BMP-4-stimulated OPG release by inhibiting the Smad1/5/8 signaling pathway, with similar inhibitory effects observed for fluvoxamine and sertraline.
BIOCHEMISTRY AND CELL BIOLOGY
(2021)
Article
Oncology
Guiping Lu, Zhuowang Ge, Xinyuan Chen, Yue Ma, Ancai Yuan, Yuquan Xie, Jun Pu
Summary: In this study, it was found that BMP6 expression increased after myocardial infarction, and BMP6(-/-) mice showed more significant cardiac dysfunction and lower survival rates after MI. Additionally, BMP6(-/-) mice exhibited larger infarct area, increased fibrosis, and more pronounced inflammatory infiltration. Mechanistic studies revealed that BMP6 decreases collagen secretion in fibroblasts. Lastly, it was found that rhBMP6 can alleviate ventricular remodeling abnormalities after myocardial infarction.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Yoshiaki Soejima, Nahoko Iwata, Nanako Nakayama, Shinichi Hirata, Yasuhiro Nakano, Koichiro Yamamoto, Atsuhito Suyama, Kohei Oguni, Takahiro Nada, Satoshi Fujisawa, Fumio Otsuka
Summary: Orexin plays a key role in regulating sleep, wakefulness and feeding behavior. This study shows that Orexin regulates gonadotropin expression by interacting with GnRH and the pituitary BMP system, and this regulation involves clock gene expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Engineering, Biomedical
Xinna Wang, Bo Gao, Barbara P. Chan
Summary: The study presents a mask-free, non-contact and biocompatible multiphoton microfabrication and micropatterning technology for engineering soluble cell niches. Immobilizing biotinylated BMP-2 on micro-printed neutravidin micropatterns resulted in a more sustained and higher level of downstream signaling in C2C12 cells. This work establishes a universal platform for engineering cell niches and contributes to modeling signal transduction and drug screening using native soluble cell niches.
Article
Cell Biology
Lishan Zhang, Ziqi Fang, Guangdong Cheng, Mengting He, Yanliang Lin
Summary: A novel missense mutation (NM_000523: exon2: c.G917T: p.R306L) of Hoxd13 gene was identified in a Chinese family with synpolydactyly (SPD). Mice carrying the corresponding Hoxd13 mutation exhibited synpolydactyl phenotype. Further analysis revealed that this mutation promoted osteoclast differentiation and bone loss by regulating Smad5/p65/c-Fos/Rank axis, providing new insights into the development of SPD.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Magdalena Wytrwal, Malgorzata Sekula-Stryjewska, Agata Pomorska, Ewa Oclon, Ewa Zuba-Surma, Szczepan Zapotoczny, Krzysztof Szczubialka
Summary: This study investigated the covalent binding of recombinant human bone morphogenetic protein-2 and -7 in stem cells and its effects on cell adhesion, migration, and osteogenesis. The presence of both proteins enhanced cell adhesion but limited cell motility, while the presence of single proteins promoted cell migration activity. Additionally, the coexistence of the proteins significantly increased early osteogenic marker expression.
Article
Biochemistry & Molecular Biology
Yoshiaki Soejima, Nahoko Iwata, Yasuhiro Nakano, Koichiro Yamamoto, Atsuhito Suyama, Takahiro Nada, Fumio Otsuka
Summary: The study examined the roles of Clock genes and BMP system in regulating gonadotropin secretion by GnRH using mouse L beta T2 cells. The results showed that LH beta mRNA expression in L beta T2 cells changed over time and was influenced by Bmal1 and Clock. ERK and BMPs were found to be involved in the regulation of LH beta mRNA expression at different stages after GnRH stimulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jay C. Groppe, Guorong Lu, Mary R. Tandang-Silvas, Anupama Pathi, Shruti Konda, Jingfeng Wu, Viet Q. Le, Andria L. Culbert, Eileen M. Shore, Kristi A. Wharton, Frederick S. Kaplan
Summary: Although structurally similar to type II counterparts, type I or activin receptor-like kinases (ALKs) have a unique helix-loop-helix (HLH) element that plays an active role in inhibiting the kinase activity. A single mutation in the codon of the penultimate residue causes milder activation of ACVR1/ALK2 and leads to abnormal bone deposition. The HLH subdomain of the mutant protein suppresses the enzyme's activity and affects the ATP-binding and polypeptide-interacting active site, resulting in the gain of function responsible for sporadic heterotopic ossification.
Article
Biochemistry & Molecular Biology
Satoshi Fujisawa, Motoshi Komatsubara, Naoko Tsukamoto-Yamauchi, Nahoko Iwata, Takahiro Nada, Jun Wada, Fumio Otsuka
Summary: Orexin A enhances POMC transcription in corticotrope cells by upregulating CRHR signaling and downregulating BMP-Smad signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Polymer Science
Oana Gherasim, Alexandru Mihai Grumezescu, Valentina Grumezescu, Ecaterina Andronescu, Irina Negut, Alexandra Catalina Birca, Bianca Galateanu, Ariana Hudita
Summary: Osteoconductive and osteoinductive coatings are effective strategies for enhancing the integration of metallic implants with bone. Composite materials based on PLA and HAp benefit bone cell development, while the addition of osteogenic proteins contributes to new bone formation. Laser-processed composites show superior ability to promote osteoprogenitor cell adhesion, viability, and proliferation.
Article
Engineering, Biomedical
Sarah A. Schoonraad, Alan A. Jaimes, Arjun J. X. Singh, Kiera J. Croland, Stephanie J. Bryant
Summary: This study investigates the osteogenic effects of tethered BMP-2 and BMP-9 on human MSCs encapsulated in a hydrogel. The results show that tethered BMP-2 and BMP-9 both effectively enhance osteogenesis of MSCs, leading to a mature osteoblast phenotype.
ACTA BIOMATERIALIA
(2023)
Article
Cell Biology
Sayako Katada, Jun Takouda, Takumi Nakagawa, Mizuki Honda, Katsuhide Igarashi, Takuya Imamura, Yasuyuki Ohkawa, Shoko Sato, Hitoshi Kurumizaka, Kinichi Nakashima
Summary: This study reveals a sophisticated regulation of NPC fate change during cortical development, where the interplay between cell-extrinsic cues and -intrinsic epigenetic programs plays a critical role. Smads, downstream transcription factors from BMP signaling, target different genomic regions in neurogenic and gliogenic NPCs, highlighting the importance of their role in regulating NPC properties.
GENES & DEVELOPMENT
(2021)
Article
Plant Sciences
Owen G. Osborne, Mariya P. Dobreva, Alexander S. T. Papadopulos, Magna S. B. de Moura, Alexandre T. Brunello, Luciano P. de Queiroz, R. Toby Pennington, Jon Lloyd, Vincent Savolainen
Summary: The architecture of root systems is crucial for plant fitness, competition, and ecosystem processes. However, the difficulty in mapping roots hinders the study of these processes. This study developed a scalable sequencing-based method to map individual tree root systems across multiple species, providing a more efficient and applicable approach for ecological research.
Article
Multidisciplinary Sciences
Catherine Dupont, Olivier J. M. Schaffers, Beatrice F. Tan, Sarra Merzouk, Eric M. Bindels, An Zwijsen, Danny Huylebroeck, Joost Gribnau
Summary: This study presents the murine embryonic-trophoblast-extra-embryonic endoderm (ETX) model as an integrated stem cell-based model to study early postimplantation development. By using transgenic Gata6-overproducing ESCs and modified assembly and culture conditions, ETX embryoids that accurately mimic in vivo postimplantation mouse development can be generated.
Article
Rheumatology
Reem Assi, Chahrazad Cherifi, Frederique M. F. Cornelis, Qiongfei Zhou, Lies Storms, Sofia Pazmino, Rodrigo Coutinho de Almeida, Ingrid Meulenbelt, Rik J. J. Lories, Silvia Monteagudo
Summary: The methylation of H3K79me is reduced in osteoarthritis. Histone demethylase families, such as Jumonji-C and KDM2/7, can increase the levels of H3K79me and targeting KDM2/7 can protect joints against osteoarthritis.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Biotechnology & Applied Microbiology
Delilah Hendriks, Jos F. Brouwers, Karien Hamer, Maarten H. Geurts, Lea Luciana, Simone Massalini, Carmen Lopez-Iglesias, Peter J. Peters, Maria J. Rodriguez-Colman, Susana Chuva de Sousa Lopes, Benedetta Artegiani, Hans Clevers
Summary: Organoid models of early liver disease, such as nonalcoholic fatty liver disease (NAFLD), are valuable for target discovery and drug screening. Using human fetal hepatocyte organoids, the first stage of NAFLD, steatosis, was successfully modeled with various triggers. Screening of drug candidates identified compounds that effectively resolved steatosis by repressing de novo lipogenesis. The study also introduced FatTracer, a CRISPR screening platform, to identify steatosis modulators and potential targets.
NATURE BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Nannan Guo, Na Li, Li Jia, Qinyue Jiang, Mette Schreurs, Vincent van Unen, Susana M. Chuva de Sousa Lopes, Alexandra A. Vloemans, Jeroen Eggermont, Boudewijn Lelieveldt, Frank J. T. Staal, Noel F. C. C. de Miranda, M. Fernanda Pascutti, Frits Koning
Summary: This study reveals the changes in immune subsets in the developing human foetal intestine, showing the sequential appearance of different types of immune cells between gestational weeks 14 and 22. The presence of immune subset-committed cells capable of local proliferation suggests their important role in the development of organized immune structures and potential influence on microbial colonization after birth.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Laura Ruland, Francesco Andreatta, Simone Massalini, Susana Chuva de Sousa Lopes, Hans Clevers, Delilah Hendriks, Benedetta Artegiani
Summary: By engineering human organoids to reflect different genetic backgrounds of fibrolamellar carcinoma (FLC), the authors demonstrate that hepatocytes can be a cell-of-origin of FLC that transdifferentiate into ductal/progenitor like cells due to combined BAP1 and PRKAR2A loss.
NATURE COMMUNICATIONS
(2023)
Review
Oncology
Sara Vasconcelos, Carla Canicais, Susana M. Chuva de Sousa Lopes, C. Joana Marques, Sofia Doria
Summary: The placenta is crucial for mammalian embryo and fetal development. Understanding the role of epigenetics, including DNA hydroxymethylation, in placental development and function can help improve diagnosis and treatment of obstetric complications. This review focuses on DNA hydroxymethylation and its regulators in both human and mouse placenta, along with its relevance to genomic imprinting and pregnancy complications such as intrauterine growth restriction, preeclampsia, and pregnancy loss. The findings suggest that DNA hydroxymethylation plays a dynamic role in trophoblast cell differentiation during gestation and may be an important factor in gene expression regulation in the placenta.
CLINICAL EPIGENETICS
(2023)
Article
Genetics & Heredity
Judith C. C. Birkhoff, Anne L. L. Korporaal, Rutger W. W. Brouwer, Karol Nowosad, Claudia Milazzo, Lidia Mouratidou, Mirjam C. G. N. van den Hout, Wilfred F. J. van IJcken, Danny Huylebroeck, Andrea Conidi
Summary: Functional studies have shown that Zeb2 plays a crucial role in controlling cell fate decisions and differentiation. By editing mouse embryonic stem cells, researchers were able to identify DNA-binding sites for Zeb2 and found that autoregulation of Zeb2 is necessary for proper differentiation. Furthermore, the study also provided insights into developmental disorders and monogenic syndromes.
Review
Multidisciplinary Sciences
Varsha Jain, Susana M. Chuva de Sousa M. Lopes, Mohammed A. Benotmane, Vittore Verratti, Rod T. Mitchell, Jan-Bernd Stukenborg
Summary: This review summarises key aspects of the first reproductive and developmental systems Science Community White Paper, supported by the European Space Agency (ESA). The white papers aim to reflect on the implications of space travel on the male and female reproductive systems and explore how this may impact society on Earth.
Article
Multidisciplinary Sciences
Annie S. P. Yang, Devanjali Dutta, Kai Kretzschmar, Delilah Hendriks, Jens Puschhof, Huili Hu, Kim E. Boonekamp, Youri van Waardenburg, Susana M. Chuva de Sousa Lopes, Geert-Jan van Gemert, Johannes H. W. de Wilt, Teun Bousema, Hans Clevers, Robert W. Sauerwein
Summary: Researchers have found that hepatocytes derived from human hepatocyte organoids (HepOrgs) can support the development of Plasmodium falciparum, and have identified the importance of the host factor scavenger receptor B1 (SRB1) in parasite development.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Esmee K. van der Ploeg, Lisette Krabbendam, Heleen Vroman, Menno van Nimwegen, Marjolein J. W. de Bruijn, Geertje M. de Boer, Ingrid M. Bergen, Mirjam Kool, Gerdien A. Tramper-Standers, Gert-Jan Braunstahl, Danny Huylebroeck, Rudi W. Hendriks, Ralph Stadhouders
Summary: CD8+ cytotoxic T cells can also produce type-2 cytokines in severe asthma patients, and their abundance is associated with increased disease burden, higher exacerbation rates, and steroid insensitivity. The type-2 skewing of lung Tc cells in asthma is controlled by conventional type-1 dendritic cells and IFN gamma. Interleukin-33 (IL-33) critically promotes type-2 cytokine production by lung Tc cells in experimental allergic airway inflammation.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Anne Onrust-van Schoonhoven, Marjolein J. W. de Bruijn, Bernard Stikker, Rutger W. W. Brouwer, Gert-Jan Braunstahl, Wilfred F. J. van IJcken, Thomas Graf, Danny Huylebroeck, Rudi W. Hendriks, Gregoire Stik, Ralph Stadhouders
Summary: This study reveals that human CD4(+) memory T helper 2 (T(H)2) cells undergo chromatin reprogramming at both one-dimensional and three-dimensional levels to efficiently recall an inflammatory transcriptional program. Distal enhancers organized in long-range three-dimensional chromatin hubs are responsible for epigenetically priming recall genes in memory T(H)2 cells. Key recall genes are precisely controlled within dedicated topologically associating domains through activation-associated promoter-enhancer interactions mediated by AP-1 transcription factors. Aberrant transcriptional control of recall responses is linked to chronic inflammation in resting memory T(H)2 cells from asthma patients. These findings highlight the importance of stable multiscale reprogramming of chromatin organization in T cell immunological memory and dysfunction.
SCIENCE IMMUNOLOGY
(2023)
Article
Orthopedics
Rebecca J. Williams, Lisanne T. Laagland, Frances C. Bach, Lizzy Ward, Wilson Chan, Vivian Tam, Adel Medzikovic, Shaghayegh Basatvat, Lily Paillat, Nicolas Vedrenne, Joseph W. Snuggs, Deepani W. Poramba-Liyanage, Judith A. Hoyland, Danny Chan, Anne Camus, Stephen M. Richardson, Marianna A. Tryfonidou, Christine L. Le Maitre
Summary: This article provides key recommendations and methodologies for the isolation, manipulation, and characterization of notochordal cells (NCs) from early developmental stages to skeletal maturation. It offers a road map for in vitro studies of NCs and their potential in regenerative therapies.
Review
Biotechnology & Applied Microbiology
Julieta S. Del Valle, Susana Chuva de Sousa M. Lopes
Summary: Ovarian dysfunction has significant consequences for female health, including infertility and conditions such as osteoporosis and cardiovascular disease. The development of bioengineered three-dimensional (3D) ovarian models provides a valuable tool for studying ovarian physiology and pathology, as well as potential alternatives for fertility preservation and restoration of ovarian function. This review focuses on the latest advances in 3D ovarian platforms, including modeling female reproduction, physiology, ovarian cancer, and drug screening.
BIOENGINEERING-BASEL
(2023)
Article
Cell & Tissue Engineering
L. Paillat, K. Coutant, M. Dutilleul, S. Le Lay, A. Camus
Summary: Intervertebral disc degeneration (IDD) involves changes in cellular composition and factors secreted by notochordal cells (NCs) are essential for maintaining a healthy intervertebral disc (IVD). However, the study of NCs is limited due to a lack of native cells and cell models. In this study, NP cells were isolated from postnatal mouse spines and cultured into micromasses, demonstrating maintenance of phenotypic characteristics and the presence of proteins of interest. This 3D culture model allows for future exploration of NC biology and signaling pathways in IVD homeostasis and disc repair.
EUROPEAN CELLS & MATERIALS
(2023)