Connective tissue disorders research

GL-0001, a first-in-class dual GIP/GLP-2 analogue, reduces bone fragility by enhancing bone material properties in a murine model of type III osteogenesis imperfecta

GL-0001 improves bone fragility in a mouse model of osteogenesis imperfecta by enhancing bone material properties and growth, unlike bisphosphonates which primarily affect bone mass.

A cell death-independent role for MLKL in TGF-β receptor recycling in Marfan syndrome

This study identifies a non-cell death role for MLKL in TGF-β receptor recycling and aortic integrity in Marfan syndrome.

Angiotensin II Promotes Mitral Valve and Left Atrial Pathology in Fibrillin-1C1041G/+ Mice

This study shows that Angiotensin II exacerbates mitral valve and left atrial pathology in Fbn1C1041G/+ mice, while AGT inhibition does not alter the phenotype.

Thoracic Aortic Disease in Genetic Syndromes Beyond Established Aortopathy Genes

The paper identifies de novo pathogenic variants in syndromic genes associated with thoracic aortic disease beyond established aortopathy genes.

VGLL4 promotes thoracic aortic aneurysm and dissection by disrupting extracellular matrix homeostasis via WISP1-mediated TIMP3/MMP9 imbalance

This study identifies VGLL4 as a mechanosensitive regulator of TAAD by disrupting ECM homeostasis through the WISP1-TIMP3/MMP9 axis.

Blocking Compensatory Matrix Cross-Linking Accelerates ThoracicAortopathy in a Mouse Model of Marfan Syndrome

This study shows that blocking lysyl oxidase in Marfan syndrome mice under hypertension worsens aortic disease, highlighting the protective role of collagen cross-linking.

Marfan Patient iPSC-Derived Endothelial Cells Carrying FBN1 Variants Reveal Endothelial Dysfunction

This study uses iPSC-derived endothelial cells from Marfan syndrome patients to show impaired inflammatory resolution and endothelial dysfunction linked to FBN1 variants.

Patient-specific zebrafish models reveal a complex phenotypic spectrum in NBAS-associated Atypical Osteogenesis Imperfecta

The paper uses zebrafish models to study NBAS variants in atypical Osteogenesis Imperfecta, showing different phenotypes based on variant type.

Functional surrogacy enables Vascular Ehlers-Danlos Syndrome modelling in zebrafish in the absence of a COL3A1 ortholog

The paper develops a zebrafish model to assess COL3A1 variants of uncertain significance by using functional surrogacy through col5a1 knockout and human COL3A1 mRNA co-injection.

Smooth Muscle Cell-Specific TGFβ2 Protects Against Thoracic Aortic Aneurysm and Dissection in Mice

This study shows that TGFβ2 from vascular smooth muscle cells is essential for aortic wall integrity, and its loss leads to aneurysms and dissection in mice.

A Marfan-Associated FBN1 Nonsense Mutation Mouse Model Reveals Adventitial Inflammation During Aneurysm Progression

This paper develops a mouse model with a FBN1 nonsense mutation to study aneurysm progression, finding that adventitial inflammation contributes to aortic aneurysm rupture.

Complex Genetics and Regulatory Drivers of Hypermobile Ehlers-Danlos Syndrome: Insights from Genome-Wide Association Study Meta-analysis

This study identifies two genome-wide significant loci associated with hypermobile Ehlers-Danlos syndrome, implicating neuroimmune and pain signaling pathways and highlighting genetic correlations with multiple comorbid conditions.

Novel Genetic Variants of Thoracic Aortic Aneurysm and Dissection: Evidence from a Japanese Community-Based Cohort

This study identifies rare homozygous variants in TAAD-related genes as significant predictors of TAAD-related mortality in a Japanese population.

Impact of the maternal environment on cardiovascular features of the offspring in a mouse model of Marfan syndrome

This study investigates how the maternal environment affects cardiovascular traits in MFS offspring using a mouse model, finding maternal inheritance leads to earlier aortic enlargement and persistent cardiac issues.

Nanoscale Structural and Functional Impacts of Disease-Associated Collagen Mutations

This study examines how collagen mutations affect fibril structure and integrin interactions, showing that different mutations lead to distinct structural and functional changes in collagen.

Generation and characterization of Induced Pluripotent Stem Cell models with SMAD3 mutations to study the molecular mechanism of Loeys-Dietz Syndrome Type III aneurysm formation

This study generates and characterizes induced pluripotent stem cell models with SMAD3 mutations to investigate LDS3 aneurysm formation mechanisms.

Growth Arrest of Thoracic Aortic Aneurysms in Aging Marfan Mice

The paper investigates growth arrest in thoracic aortic aneurysms of aging Marfan mice, identifying gene expression and proteomic changes that may contribute to disease stabilization.

Loss of function variants in ADAMTS6: Connective tissue, Heart defect, thoracic Aortic aneurysm and Neuro developmental Syndrome (CHANS)

The paper identifies loss-of-function variants in ADAMTS6 in patients with vascular and neurodevelopmental disorders, linking them to connective tissue defects and proposing a new syndrome called CHANS.

Decoding Phenotypic Variability in Osteogenesis Imperfecta: Zebrafish as a Model for Molecular and Ultrastructural Insights.

This study uses zebrafish models to link genetic mutations in type I collagen to phenotypic severity in OI, identifying biomarkers and mechanisms of variability.

Combined ADAMTS10 and ADAMTS17 inactivation exacerbates bone shortening and skin phenotypes

This study shows that inactivating both ADAMTS10 and ADAMTS17 in mice causes severe bone shortening and skin issues, suggesting they regulate ECM formation and chondrocyte function.

Dysregulated Proteins in Plasma Distinguishing Syndromic from Non-syndromic Heritable Thoracic Aortic Disease

Apoptosis is increased in cortical neurons of female Marfan Syndrome mice

This study finds increased apoptosis in cortical neurons of female MFS mice compared to controls, with elevated BDNF levels in both sexes.

Cerebral Microvascular Density, Permeability of the Blood-Brain Barrier, and Neuroinflammatory Responses Indicate Early Aging Characteristics in a Marfan Syndrome Mouse Model

This study investigates cerebrovascular and neuroinflammatory changes in a Marfan Syndrome mouse model, finding premature aging characteristics in the brain similar to aged controls.

The chemical chaperone 4-phenylbutyric acid rescues molecular cell defects of COL3A1 mutations that cause vascular Ehlers Danlos Syndrome

This study shows that 4-phenylbutyric acid rescues molecular defects in COL3A1 mutations causing vEDS by reducing ER stress and improving collagen secretion.

Integrated Stress Response Triggered by Excessive Glycosylation Drives Thoracic Aortic aneurysm

This study identifies the HBP-ISR axis as a driver of thoracic aortic aneurysm in Marfan Syndrome, showing that targeting this pathway can reverse aortic dilation in mice and is associated with human TAAD.

3D-bioprinted patient-specific organotypic bone model mimicking mineralization dysregulation in FKBP10-related osteogenesis imperfecta

The paper uses 3D-bioprinted bone models to show dysregulated mineralization in FKBP10-related osteogenesis imperfecta compared to healthy controls.

Biallelic Variants in CCN2 Underlie an Autosomal Recessive Kyphomelic Dysplasia

This study identifies biallelic CCN2 variants as the cause of autosomal recessive kyphomelic dysplasia through clinical, genetic, and zebrafish model analyses.

Dominant nonsense mutations in efemp1 alter vertebral and craniofacial characteristics in adult zebrafish

Pleiotropic effects of a recessive COL1A2 mutation occurring in a mouse model of severe osteogenesis imperfecta

This study investigates the pleiotropic effects of a recessive COL1A2 mutation in OIM mice, revealing mechanisms of bone fragility in severe osteogenesis imperfecta.

Early mechanisms of aortic failure in a zebrafish model for thoracic aortic dissection and rupture

This study develops a zebrafish model of thoracic aortic dissection and rupture by knocking out SMAD3 and SMAD6 genes, revealing novel pathways and potential therapeutic targets.