Review
Cell Biology
Shaina P. Royer, Sangyoon J. Han
Summary: Ehlers-Danlos Syndromes (EDS) are a group of connective tissue disorders characterized by skin stretchability, joint hypermobility, and instability, possibly associated with reduced tissue stiffness. Comorbidities include mast cell activation syndrome and impaired wound healing, and potential mechanobiological mechanisms need further investigation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Delfien Syx, Sarah Delbaere, Catherine Bui, Adelbert De Clercq, Goran Larson, Shuji Mizumoto, Tomoki Kosho, Sylvie Fournel-Gigleux, Fransiska Malfait
Summary: Proteoglycans, consisting of a core protein and glycosaminoglycan chains, play versatile functions in physiological and pathological processes. The biosynthesis of glycosaminoglycan chains is a complex process involving various enzymes. Deficiencies in these biosynthetic enzymes can lead to severe disorders, such as the Ehlers-Danlos syndromes. This review summarizes the consequences of glycosaminoglycan deficiency in specific types of Ehlers-Danlos syndromes and provides insights into the underlying pathophysiological mechanisms.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yoshihiro Ishikawa, Arkadiusz Bonna, Douglas B. Gould, Richard W. Farndale
Summary: Mutations in the FKBP14 gene result in kyphoscoliotic Ehlers-Danlos Syndrome (EDS), and FKBP22 selectively binds to collagens III, IV, VI, and X. The binding distribution of FKBP22 along the collagen helix and its correlation with positive peptide charge have been observed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Albert Amberger, Johanna Pertoll, Pia Traunfellner, Ines Kapferer-Seebacher, Heribert Stoiber, Lars Klimaschewski, Nicole Thielens, Christine Gaboriaud, Johannes Zschocke
Summary: Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal dominant connective tissue disorder characterized by early-onset periodontitis, thin and fragile gums, and other manifestations such as easy bruising and joint hypermobility. pEDS is caused by missense mutations in C1R and C1S genes, which lead to inadequate degradation of matrix proteins. This results in fast collagen turnover and loose compaction of tissues, contributing to the EDS phenotype.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Anna Maria Comberiati, Ludovico Iannetti, Raffaele Migliorini, Marta Armentano, Marika Graziani, Luca Celli, Anna Zambrano, Mauro Celli, Magda Gharbiya, Alessandro Lambiase
Summary: This study aims to evaluate ocular motility (OM) abnormalities associated with Ehlers-Danlos Syndrome (EDS). Patients with EDS underwent a complete orthoptic examination, and various OM alterations were observed in these patients. The results show that superior and medial rectus muscle hypofunction, as well as other abnormalities, are common in patients with EDS.
APPLIED SCIENCES-BASEL
(2023)
Article
Multidisciplinary Sciences
Hao-Han Chang, Yung-Shun Juan, Ching-Chia Li, Hsiang-Ying Lee, Jian-Han Chen
Summary: This study showed that male patients with congenital collagen diseases are at a significantly higher risk of developing inguinal hernias compared to those without these diseases, regardless of age.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Friedrich Stock, Marcel Hanisch, Sarah Lechner, Saskia Biskup, Axel Bohring, Johannes Zschocke, Ines Kapferer-Seebacher
Summary: This is an extremely rare case of combined classical Ehlers-Danlos syndrome (EDS) and periodontal EDS, with a heterozygous mutation in the COL5A1 gene identified in the affected German family. The clinical presentation includes generalized joint hypermobility, hyperelastic skin, and atrophic scarring as major criteria for classical EDS, as well as early severe periodontitis and generalized lack of attached gingiva indicative of periodontal EDS.
Review
Cell Biology
Sabeeha Malek, Darius V. Koster
Summary: Ehlers-Danlos syndromes are a group of disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility, most of which are caused by mutations affecting collagen structure. The pathogenesis of these disorders remains poorly understood, but recent research suggests a possible link to dysfunctional fibroblasts and abnormalities in cell adhesion and cytoskeleton dynamics.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Health Care Sciences & Services
Alexandra Menni, Georgios Tzikos, Alexandros Sarafis, Athina Ververi, George Chatziantoniou, Vasileios Rafailidis, Stavros Panidis, Patroklos Goulas, Eleni Karlafti, Stylianos Apostolidis, Olga Giouleme, Antonios Michalopoulos, Daniel Paramythiotis
Summary: This article describes a case of vascular type Ehlers-Danlos syndrome (vEDS) with coexisting segmental absence of intestinal musculature, and reviews the existing literature on this topic. The diagnosis of vEDS was confirmed through genetic testing and conservative treatment was adopted. A comprehensive review of the international literature revealed 34 reported cases of bowel perforation in vEDS so far.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Orthopedics
Ke Lu, Feng Ma, Dan Yi, Huan Yu, Liping Tong, Di Chen
Summary: Temporomandibular joint (TMJ) osteoarthritis (OA) is a TMJ disorder characterized by pain, movement limitation, cartilage degeneration, and joint dysfunction. This review article summarizes recent findings on signaling pathways involved in TMJ OA development and progression, highlighting the importance of understanding these pathways for potential therapeutic strategies. Multiple signaling pathways, including Wnt/beta-catenin, TGF-beta and BMP, Indian Hedgehog, FGF, NF-kappa B, and Notch pathways, are implicated in the pathological process of TMJ OA.
JOURNAL OF ORTHOPAEDIC TRANSLATION
(2022)
Article
Genetics & Heredity
Jared A. Jaffey, Garrett Bullock, Juyuan Guo, Tendai Mhlanga-Mutangadura, Dennis P. O'Brien, Joan R. Coates, Rochelle Morrissey, Robert Hutchison, Kevin S. Donnelly, Leah A. Cohn, Martin L. Katz, Gary S. Johnson
Summary: This study reports the discovery of ADAMTS2 gene variants in EDS-affected dogs, which lead to severe skin fragility and other characteristics. The findings expand the spectrum of clinical features of canine EDS.
Article
Engineering, Biomedical
Rong Ren, Jiahao Zhou, Yixin Sun, Wael Telha, Ning Song, Yanjing Zhan, Songsong Zhu, Nan Jiang
Summary: This study characterizes and compares the TMJ condylar cartilage of six different species from a materials science perspective. It reveals that the structure, composition, and mechanical properties of TMJ condylar cartilage differ between species, with differences in fibril diameter and GAGs content being the main factors influencing the mechanical properties. Pigs have the most similar condylar cartilage to humans, suggesting their suitability as an animal model for TMJ studies.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2023)
Article
Genetics & Heredity
Satoko Ishikawa, Shujiro Hayashi, Toshimi Sairenchi, Manabu Miyamoto, Shigemi Yoshihara, Gen Kobashi, Tomomi Yamaguchi, Tomoki Kosho, Ken Igawa
Summary: This study used electron microscopy to observe structural abnormalities in collagen fibrils and endoplasmic reticulum stress in skin samples from 30 vEDS patients and 48 non-vEDS patients. It found a relationship between these abnormalities and clinical symptoms, with some vEDS patients having lower coefficient of variation (COV) and experiencing fewer complications and endoplasmic reticulum stress.
FRONTIERS IN GENETICS
(2023)
Article
Dermatology
Satoko Ishikawa, Tomoki Kosho, Tomoko Kaminaga, Manabu Miyamoto, Yoichiro Hamasaki, Shigemi Yoshihara, Shujiro Hayashi, Ken Igawa
Summary: This study focuses on anomalies in collagen fiber size and the endoplasmic reticulum stress response in patients with Vascular-type Ehlers-Danlos syndrome (vEDS). The research found that ATF6 expression levels were significantly higher in the vEDS group, while COMP and COL3A1 levels were lower. The fragile collagen fibrils in vEDS might form as a result of ER stress, leading to the appearance of small, newly formed collagen fibrils.
JOURNAL OF DERMATOLOGY
(2021)
Article
Genetics & Heredity
Marlies Colman, Robin Vroman, Tibbe Dhooge, Zoe Malfait, Sofie Symoens, Birute Burnyte, Sheela Nampoothiri, Ariana Kariminejad, Fransiska Malfait, Delfien Syx
Summary: This study reports the clinical manifestations of three individuals with homozygous pathogenic FKBP14 variants, including previously reported and novel variants. Consistent clinical features of kyphoscoliosis, joint hypermobility, and muscle hypotonia were observed in these individuals. Severe vascular complications were also observed in some cases. Microcornea was identified as a previously unreported feature in this study. Immunocytochemistry studies demonstrated intracellular retention of types III and VI collagen in EDS-FKBP14.
Article
Chemistry, Multidisciplinary
Biao Han, Qing Li, Chao Wang, Pavan Patel, Sheila M. Adams, Basak Doyran, Hadi T. Nia, Ramin Oftadeh, Siyuan Zhou, Christopher Y. Li, X. Sherry Liu, X. Lucas Lu, Motomi Enomoto-Iwamoto, Ling Qin, Robert L. Mauck, Renato V. Iozzo, David E. Birk, Lin Han
Article
Anatomy & Morphology
Lauren Jeang, Byeong J. Cha, David E. Birk, Edgar M. Espana
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY
(2020)
Article
Rheumatology
Qing Li, Biao Han, Chao Wang, Wei Tong, Yulong Wei, Wei-Ju Tseng, Li-Hsin Han, X. Sherry Liu, Motomi Enomoto-Iwamoto, Robert L. Mauck, Ling Qin, Renato V. Iozzo, David E. Birk, Lin Han
ARTHRITIS & RHEUMATOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Tomohiro Yokota, Jackie McCourt, Feiyang Ma, Shuxun Ren, Shen Li, Tae-Hyung Kim, Yerbol Z. Kurmangaliyev, Rohollah Nasiri, Samad Ahadian, Thang Nguyen, Xing Haw Marvin Tan, Yonggang Zhou, Rimao Wu, Abraham Rodriguez, Whitaker Cohn, Yibin Wang, Julian Whitelegge, Sergey Ryazantsev, Ali Khademhosseini, Michael A. Teitell, Pei-Yu Chiou, David E. Birk, Amy C. Rowat, Rachelle H. Crosbie, Matteo Pellegrini, Marcus Seldin, Aldons J. Lusis, Arjun Deb
Article
Ophthalmology
Edgar M. Espana, David E. Birk
EXPERIMENTAL EYE RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Mei Sun, Eric Y. Luo, Sheila M. Adams, Thomas Adams, Yaping Ye, Snehal S. Shetye, Louis J. Soslowsky, David E. Birk
Article
Biochemistry & Molecular Biology
Yayoi Izu, Sheila M. Adams, Brianne K. Connizzo, David P. Beason, Louis J. Soslowsky, Manuel Koch, David E. Birk
Summary: Collagen XII plays dual roles in tendon development by influencing fibril packing, fiber assembly and stability, as well as regulating tenocyte organization and intercellular communication. Its deficiency results in altered cell shape, impaired cell-cell communication, and decreased tissue stiffness, indicating its crucial role in tendon structure and function. Additionally, collagen XII specifically affects tenocyte biosynthesis and provides feedback to regulate extracellular collagen I, highlighting its significance in tendon development and maintenance.
Review
Obstetrics & Gynecology
David B. Frank, Philip T. Levy, Corey A. Stiver, Brian A. Boe, Christopher W. Baird, Ryan M. Callahan, Charles V. Smith, Rachel D. Vanderlaan, Carl H. Backes
Summary: Primary pulmonary vein stenosis (PPVS) is an emerging issue among infants, with developing understanding of pathophysiological mechanisms and therapeutic strategies. Multidisciplinary teams are essential for reviewing evidence and providing a common framework for diagnosis and treatment. Institutional and multi-institutional collaboration is crucial to generate specific knowledge and advance research on this rare disease.
JOURNAL OF PERINATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Daphney R. Chery, Biao Han, Ying Zhou, Chao Wang, Sheila M. Adams, Prashant Chandrasekaran, Bryan Kwok, Su-Jin Heo, Motomi Enomoto-Iwamoto, X. Lu, Dehan Kong, Renato V. Iozzo, David E. Birk, Robert L. Mauck, Lin Han
Summary: This study identified decorin as a key determinant of cartilage pericellular matrix micromechanics and chondrocyte mechanotransduction. The absence of decorin in murine cartilage resulted in reduced micromodulus of the pericellular matrix and impaired chondrocyte mechanotransduction.
Article
Orthopedics
B. Han, Q. Li, C. Wang, P. Chandrasekaran, Y. Zhou, L. Qin, X. S. Liu, M. Enomoto-Iwamoto, D. Kong, R. V. Iozzo, D. E. Birk, L. Han
Summary: In post-traumatic osteoarthritis (PTOA), decorin plays a more crucial role than biglycan in regulating cartilage degeneration, while biglycan is more important in regulating subchondral bone structure. The two have distinct activities and modest synergy in the pathogenesis of PTOA.
OSTEOARTHRITIS AND CARTILAGE
(2021)
Article
Cell Biology
Janis Koester, Yekaterina A. Miroshnikova, Sushmita Ghatak, Carlos Andres Chacon-Martinez, Jessica Morgner, Xinping Li, Ilian Atanassov, Janine Altmueller, David E. Birk, Manuel Koch, Wilhelm Bloch, Michaela Bartusel, Carien M. Niessen, Alvaro Rada-Iglesias, Sara A. Wickstroem
Summary: The research reveals that as hair follicle stem cells age, their ability to activate bivalent genes for self-renewal and differentiation is reduced due to increased niche stiffness and subsequent epigenetic effects.
NATURE CELL BIOLOGY
(2021)
Article
Orthopedics
Zakary M. Beach, Kelsey A. Bonilla, Mihir S. Dekhne, Mei Sun, Thomas H. Adams, Sheila M. Adams, Stephanie N. Weiss, Ashley B. Rodriguez, Snehal S. Shetye, David E. Birk, Louis J. Soslowsky
Summary: It was found in mature mice that knockdown of biglycan led to extensive changes in tendon structure and mechanics, while knockdown of decorin had minimal effects. Specifically, biglycan knockdown resulted in reductions in several mechanical parameters and increased collagen fiber realignment during loading. Furthermore, both decorin and biglycan knockdown led to similar alterations in tendon microstructure.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2022)
Editorial Material
Critical Care Medicine
Susan M. Lin, David B. Frank
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)