Review
Oncology
Stefano Zoroddu, Irene Marchesi, Luigi Bagella
Summary: Muscle differentiation failure may involve epigenetic systems and the PRC2 complex. Research has shown that EZH2 is often deregulated in rhabdomyosarcoma and is associated with tumor malignancy.
CLINICAL EPIGENETICS
(2021)
Article
Biochemistry & Molecular Biology
Carmen Nunez-Carro, Margarita Blanco-Blanco, Tatiana Montoya, Karla M. Villagran-Andrade, Tamara Hermida-Gomez, Francisco J. Blanco, Maria C. de Andres
Summary: Osteoarthritis is a chronic disease that affects articular cartilage and leads to its degeneration. Recent research has shown the importance of the interplay between inflammatory processes and epigenetic regulation in the development of osteoarthritis. However, the lack of specific protocols to extract histones from human articular cartilage has hindered further investigation in this area.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Patsy Gomez-Picos, Katie Ovens, B. Frank Eames
Summary: This study investigates the appearance of cartilage at different parts of the vertebrate body during evolution. The researchers propose that a core gene regulatory network (GRN) driving chondrocyte differentiation was co-opted by different embryonic populations. By analyzing chondrocyte transcriptomes in the developing chick, the study reveals a high degree of conservation in gene expression between limb and head chondrocytes, suggesting the same core GRN was used when cartilage appeared in different regions of the skeleton. The study highlights the importance of a core transcriptional program in cartilage differentiation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yang Yi, Yanqiang Li, Chao Li, Longxiang Wu, Dongyu Zhao, Fuxi Li, Ladan Fazli, Rui Wang, Long Wang, Xuesen Dong, Wei Zhao, Kaifu Chen, Qi Cao
Summary: CDCA8 overexpression is associated with poor clinical outcome in patients with prostate cancer, and EZH2 is responsible for CDCA8 activation in PCa.
Article
Oncology
Weihang Li, Ziyi Ding, Yunlong Zhao, Min Jiang, Shilei Zhang, Hongzhe Zhao, Ke Lei, Rui Xu, Yingjing Zhao, Dong Wang, Min Chao, Yanjiang Yin, Changbin Yang, Liang Wang, Ming Yan
Summary: EZH2 is an important cancer-related target, and its inhibitors may become new anticancer drugs. The study used virtual screening technologies to identify two potential candidate drugs with excellent pharmacological properties that can stably bind and inhibit EZH2, and in vitro experiments confirmed that one of the drugs could inhibit the proliferation and migration of osteosarcoma.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Elham Barazeghi, Per Hellman, Olov Norlen, Gunnar Westin, Peter Stalberg
Summary: The study found that EZH2 is highly expressed in small intestinal neuroendocrine tumors and plays a role in cell proliferation and apoptosis. Inhibitors specific to EZH2 and metformin show promise in inhibiting tumor growth and migration, suggesting potential therapeutic options for patients with SI-NETs.
SCIENTIFIC REPORTS
(2021)
Article
Orthopedics
K. S. M. Reed, V. Ulici, C. Kim, S. Chubinskaya, R. F. Loeser, D. H. Phanstiel
Summary: Treatment of normal human articular chondrocytes with fibronectin fragments can recapitulate key aspects of the osteoarthritis chondrocyte phenotype, showing promising potential for future osteoarthritis studies, especially considering its compatibility with genomics and genome-editing techniques.
OSTEOARTHRITIS AND CARTILAGE
(2021)
Article
Cell Biology
Maria Manou, Theodoros Loupis, Dimitrios M. Vrachnos, Nikolaos Katsoulas, Stamatios Theocharis, Dimitrios S. Kanakoglou, Efthimia K. Basdra, Christina Piperi, Athanasios G. Papavassiliou
Summary: This study investigated epigenetic regulators and histone-modifying factors in salivary gland tumors (SGTs) and found a network of interacting proteins that affect chromatin structure and histone modifications. These findings provide mechanistic insights into the molecular profile of SGTs.
Article
Multidisciplinary Sciences
Rebecca A. Lee, Maggie Chang, Nicholas Yiv, Ariel Tsay, Sharon Tian, Danielle Li, Coralie Poulard, Michael R. Stallcup, Miles A. Pufall, Jen-Chywan Wang
Summary: The classical dogma of glucocorticoid-induced insulin resistance states that it is caused by the activation of certain genes. However, this study shows that glucocorticoids can also stimulate the expression of insulin-sensitizing genes. The transcriptional co-regulator EHMT2 plays a key role in this process, as it is involved in the induction of Irs2 to restrict the extent of insulin resistance caused by glucocorticoids.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Yunshu Lu, Fenfen Gu, Yuwei Ma, Ruonan Li, Yi Luo, Xianhong Da, Lan Jiang, Xiang Li, Yan Liu
Summary: This study introduces an engineered magnetic nanodrug based on Fe3O4 vortex nanorods coated with a macrophage membrane loaded with doxorubicin (DOX) and Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) siRNA. The nanodrug exhibits excellent tissue penetration, tumor accumulation, and enhanced tumor suppression compared to chemotherapy alone, indicating the potential clinical application in triple-negative breast cancer (TNBC) therapy.
Article
Oncology
Chong Wang, Tao Wang, Kang-Jing Li, Ling-Hong Hu, Yue Li, Yu-Zhong Yu, Tao Xie, Sha Zhu, Du-Jiang Fu, Yang Wang, Xian-Zi Zeng, Feng-Ping Liu, Hong Chen, Zhe-Sheng Chen, Ning-Han Feng, Jinghua Liu, Yong Jiang, Shan-Chao Zhao
Summary: The SETD4 protein plays a crucial role in prostate cancer by catalyzing histone lysine methylation and suppressing NUPR1 transcription, leading to the inhibition of Akt signaling pathway and preventing PCa development.
Article
Biochemistry & Molecular Biology
Alice Ramesova, Barbora Vesela, Eva Svandova, Herve Lesot, Eva Matalova
Summary: The study reveals new functions of Caspase-1 in chondrocyte differentiation and lipid metabolism pathways, showing that inhibiting Caspase-1 affects the expression of Cd36 and Pparg, impacting chondrogenic nodule formation. Additionally, the downregulation of Cd36 affects Rankl and Opg oppositely to the inhibition of Caspase-1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yen-Ting Liu, Celeste Romero, Xue Xiao, Lei Guo, Xiaoyun Zhou, Mark A. Applebaum, Lin Xu, Stephen X. Skapek
Summary: CDKN2A/B deletion or silencing is common in human cancer, highlighting the importance of bypassing its tumor suppression. In childhood cancers like RMS and neuroblastoma, CDKN2A/B transcripts are expressed independently, but one, ARF, is always silenced. TGF beta can induce CDKN2A/B transcripts, but only when cells are pretreated with methyltransferase inhibitors or EZH2 inhibitors, suggesting a crosstalk between methyltransferase inhibition and TGF beta-dependent activation.
MOLECULAR AND CELLULAR BIOLOGY
(2023)
Article
Genetics & Heredity
Vahid Asimi, Abhishek Sampath Kumar, Henri Niskanen, Christina Riemenschneider, Sara Hetzel, Julian Naderi, Nina Fasching, Niko Popitsch, Manyu Du, Helene Kretzmer, Zachary D. Smith, Raha Weigert, Maria Walther, Sainath Mamde, David Meierhofer, Lars Wittler, Rene Buschow, Bernd Timmermann, Ibrahim I. Cisse, Stefan L. Ameres, Alexander Meissner, Denes Hnisz
Summary: This study reveals that degradation of the heterochromatin adapter protein TRIM28 triggers dissociation of transcriptional condensates from loci encoding pluripotency genes, and their association with transcribed retrovirus loci. Knockdown of retrovirus RNAs or forced expression of transcription factors enriched in super-enhancers can rescue the localization of condensates in TRIM28-degraded cells.
Article
Chemistry, Medicinal
Qiangsheng Zhang, Xinyi Chen, Jiaying Cao, Wan Yang, Guoquan Wan, Qiang Feng, Shuyan Zhou, Hongling Yang, Ningyu Wang, Zhihao Liu, Hongtao Xiao, Yongxia Zhu, Luoting Yu
Summary: In this study, a new series of rarely reported EZH2 covalent inhibitors were designed and synthesized. Biochemical studies and mass spectrometry revealed that SKLB-03220 could bind to the S-adenosylmethionine (SAM) pocket of EZH2. SKLB-03220 showed high potency against EZH2(MUT), while displaying weak activities against other tested histone methyltransferases (HMTs) and kinases. Moreover, SKLB-03220 exhibited significant efficacy against ovarian cancer cell lines and continuously abolished H3K27me3 even after washing out. Oral administration of SKLB-03220 also effectively inhibited tumor growth in the PA-1 xenograft model without noticeable adverse effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Genetics & Heredity
Parisa Dashti, Jeroen van de Peppel, Roman Thaler, Christopher R. Paradise, Gary S. Stein, Martin A. Montecino, Johannes P. T. M. van Leeuwen, Bram J. van der Eerden, Amel Dudakovic, Andre J. van Wijnen
Summary: This study found that Smyd2 inhibits proliferation and mineral deposition by osteoblasts, and operates parallel to the suppressive effects of Ezh2 and H3K27 trimethylation on osteoblast differentiation.
Review
Biochemistry & Molecular Biology
Jinsha Koroth, Erick O. Buko, Rebecca Abbott, Casey P. Johnson, Brenda M. Ogle, Laura S. Stone, Arin M. Ellingson, Elizabeth W. Bradley
Summary: This narrative review discusses the hallmarks of intervertebral disc degeneration, presents evidence of macrophage involvement during disc degeneration, and explores emerging research on the molecular pathways regulating macrophage functions during intervertebral disc degeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Tom Kamperman, Niels G. A. Willemen, Cindy Kelder, Michelle Koerselman, Malin Becker, Luanda Lins, Castro Johnbosco, Marcel Karperien, Jeroen Leijten
Summary: This study demonstrates that stimuli-responsive cell-adhesive micromaterials can self-assemble with cells into 3D living composite microtissues and provide control over the biomechanical and biochemical environment, influencing cell behavior.
Article
Engineering, Biomedical
Rong Wang, Xiaobin Huang, Bram Zoetebier, Pieter J. Dijkstra, Marcel Karperien
Summary: In this study, hydrogels with adjustable elasticity and degradation time were designed using the properties of hyaluronic acid and star shaped poly(ethylene glycol). The hydrogels showed biocompatibility and enhanced production of collagen type II, making them suitable as scaffolds for tissue regeneration applications.
BIOACTIVE MATERIALS
(2023)
Article
Orthopedics
Martin Husen, Goran S. van der Weiden, Roel J. H. Custers, Keshav Poudel, Michael J. Stuart, Aaron J. Krych, Daniel B. F. Saris
Summary: This study investigated the long-term clinical outcomes and patient-reported outcome measures of skeletally immature and mature patients treated with surgery for unstable osteochondritis dissecans (OCD). The results showed that surgical treatment of OCD can achieve favorable outcomes and the healing rate is not influenced by the skeletal maturity status. However, a lateral femoral condylar lesion location is associated with an increased risk of failure.
AMERICAN JOURNAL OF SPORTS MEDICINE
(2023)
Article
Orthopedics
Martin Husen, Todd A. Milbrandt, Veeraj Shah, Aaron J. Krych, Michael J. Stuart, Daniel B. F. Saris
Summary: This study assessed the outcomes of medial patellofemoral ligament (MPFL) reconstruction using allograft tendon in skeletally immature patients. It found that the procedure was safe and effective for treating patellar instability, regardless of patellar height and trochlear dysplasia. The study also identified a decrease in failure rates when MPFL reconstruction was performed together with a tibial tubercle osteotomy.
AMERICAN JOURNAL OF SPORTS MEDICINE
(2023)
Article
Orthopedics
Simon Lee, Aaron J. Krych, Annalise M. Peebles, Danielle Rider, Travis J. Dekker, Justin W. Arner, Justin J. Ernat, Ryan J. Whalen, Matthew T. Provencher
Summary: This study aimed to describe the clinical presentation, examination, and surgical outcomes of patients with humeral avulsions of the glenohumeral ligament (HAGL) lesions. The results showed that both arthroscopic and open repair techniques were effective in reducing pain and instability in patients.
AMERICAN JOURNAL OF SPORTS MEDICINE
(2023)
Article
Orthopedics
Jacob F. Oeding, Elyse J. Berlinberg, Yining Lu, Erick M. Marigi, Kelechi R. Okoroha, Christopher L. Camp, Jonathan D. Barlow, Aaron J. Krych
Summary: The purpose of this study was to evaluate the cost-effectiveness of three isolated meniscal repair (IMR) treatment strategies: platelet-rich plasma (PRP)-augmented IMR, IMR with a marrow venting procedure (MVP), and non-augmented IMR. The results showed that IMR with biological augmentation (MVP or PRP) resulted in a higher number of quality-adjusted life-years (QALYs) and lower costs than non-augmented IMR, suggesting that biological augmentation is cost-effective. However, IMR with an MVP was determined to be the overall cost-effective treatment strategy in young adult patients with isolated meniscal tears based on the willingness-to-pay threshold.
ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY
(2023)
Editorial Material
Orthopedics
Andre J. van Wijnen, Eric A. Lewallen
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
(2023)
Article
Chemistry, Multidisciplinary
Maurice C. E. van Dalen, Marcel Karperien, Mireille M. A. E. Claessens, Janine N. Post
Summary: The study investigates the use of amyloid fibril-based scaffolds to stimulate chondrocytes for the formation of articular cartilage. Different proteins were induced to self-assemble into amyloid fibrils and form micron scale amyloid networks resembling cartilage extracellular matrix. The results show that lysozyme amyloid micronetworks support chondrocyte viability and extracellular matrix deposition, while alpha-synuclein and beta-lactoglobulin only maintain cell viability.
Article
Biochemistry & Molecular Biology
Ravi Maisuria, Andrew Norton, Cynthia Shao, Elizabeth W. Bradley, Kim Mansky
Summary: This study aims to determine the role of MEF2C in osteoclast differentiation and analyze the skeletal phenotype of Mef2c-cKO mice. The results suggest that MEF2C is critical for osteoclastogenesis and its dysregulation leads to a sex-specific osteopenic phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Stephane Blouin, Farzaneh Khani, Phaedra Messmer, Paul Roschger, Markus A. Hartmann, Andre J. van Wijnen, Roman Thaler, Barbara M. Misof
Summary: Vitamin C is crucial for bone health and low levels of serum Vitamin C increase the risk of skeletal fractures. This study examined the effects of Vitamin C on femoral structure, bone formation, and bone mineralization density distribution in mice. The results showed that Vitamin C depletion significantly reduced cortical thickness and bone volume, as well as diminished the amount of newly formed bone tissue. Additionally, Vitamin C supplementation led to higher calcium concentrations and suggested a longer bone tissue age. Female mice were found to be more sensitive to Vitamin C deficiency. These findings highlight the key role of Vitamin C in bone formation rate and its potential in preventing bone-degenerative diseases, especially in females.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Orthopedics
Quinn J. J. Johnson, Mohamed S. S. Jabal, Alexandra M. M. Arguello, Yining Lu, Kevin Jurgensmeier, Bruce A. A. Levy, Christopher L. L. Camp, Aaron J. J. Krych
Summary: The purpose of this study was to determine the incidence of reoperation after anterior cruciate ligament reconstruction and identify predictive factors using machine learning methods. The results showed that machine learning models outperformed traditional statistics and identified several predictive factors, including systemic inflammatory disease, distal tear location, concomitant medial collateral ligament repair, higher pain score, hamstring autograft, tibial fixation via radial expansion device, younger age, and concomitant meniscal repair.
KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY
(2023)
Article
Engineering, Biomedical
Nuno Araujo-Gomes, Barbara Zoetebier-Liszka, Bas van Loo, Malin Becker, Suzanne Nijhuis, Alexandra M. Smink, Bart J. de Haan, Paul de Vos, Marcel Karperien, Jeroen Leijten
Summary: Transplantation of microencapsulated pancreatic cells using monodisperse PEG-TA microgels is a promising therapy for T1DM. The microgels provide immunoprotection to transplanted cells and maintain their viability and function. These microencapsulated beta-cells are able to rapidly self-assemble into islet-sized spheroids, show limited immunogenicity, and remain glucose responsive both in vitro and in vivo.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Engineering, Biomedical
Castro Johnbosco, Lisanne Karbaat, Nicoline M. Korthagen, Kelly Warmink, Michelle Koerselman, Katja Coeleveld, Malin Becker, Bas van Loo, Bram Zoetebier, Sanne Both, Harrie Weinans, Marcel Karperien, Jeroen Leijten
Summary: This study investigates the effect of micromaterial composition and concentration on the therapeutic outcome of intra-articular injections of microencapsulated stem cells for the treatment of osteoarthritis. The results demonstrate that different polymer compositions and concentrations can significantly alter the metabolic activity and secretome of MSCs, as well as the retention time and biodistribution within the joint. Furthermore, the study shows that the different microgel formulations have a material-dependent effect on reducing cartilage degradation and matrix loss in rat joints with osteoarthritis.
MATERIALS TODAY BIO
(2023)