Multicentric osteolysis with nodulosis and arthropathy (MONA) with cardiac malformation, mimicking polyarticular juvenile idiopathic arthritis: case report and literature review

Castberg, Filip C.; Kjærgaard, Susanne; Mosig, Rebecca A.; Lobl, Mollie; Martignetti, Chiara R.; Martignetti, John A.; Myrup, Charlotte; Žák, Marek

doi:10.1007/s00431-013-2102-8

Cited by 26 publications

(31 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most examined individuals with an SH3PXD2B or MMP14 mutation had a broad mouth, as well as one third of examined patients with an MMP2 mutation. Finally, thick lips and either a small or heavy mandible have been reported in most examined patients with an SH3PXD2B , MMP14 , or MMP2 mutation (Al Aqeel et al, ; Al Kaissi et al, ; Azzollini et al, ; Bader‐Meunier et al, ; Bendon et al, ; Bhavani et al, ; Borrone et al, ; Castberg et al, ; Chang et al, ; Eisenstein et al, ; Ekbote et al, ; Gok et al, ; Hamel et al, ; Iqbal et al, ; Jeong et al, ; Maas et al, ; Martignetti et al, ; Mégarbané et al, ; Phadke & Dalal, ; Pichler et al, ; Prapanpoch et al, ; Rouzier et al, ; Temtamy et al, ; Ter Haar et al, ; Tuysuz et al, ; Vanatka et al, ; Van Steensel et al, ; Wilson et al, ; Winchester et al, ; Zankl et al, ; Zankl et al, ; Zrhidri et al, ).…”

Section: Discussion and Reviewmentioning

confidence: 99%

Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling

Vos

Wong

Welting

et al. 2019

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Frank-Ter Haar syndrome (FTHS), Winchester syndrome (WS), and multicentric osteolysis, nodulosis, and arthropathy (MONA) are ultra-rare multisystem disorders characterized by craniofacial malformations, reduced bone density, skeletal and cardiac anomalies, and dermal fibrosis. These autosomal recessive syndromes are caused by homozygous mutation or deletion of respectively SH3PXD2B (SH3 and PX Domains 2B), MMP14 (matrix metalloproteinase 14), or MMP2. Here, we give an overview of the clinical features of 63 previously reported patients with an SH3PXD2B, MMP14, or MMP2 mutation, demonstrating considerable clinical overlap between FTHS, WS, and MONA. Interestingly, the protein products of SH3PXD2B, MMP14, and MMP2 directly cooperate in collagen remodeling. We review animal models for these three disorders that accurately reflect the major clinical features and likewise show significant phenotypical similarity with each other. Furthermore, they demonstrate that defective collagen remodeling is central in the underlying pathology. As such, we propose a nosological revision, placing these SH3PXD2B, MMP14, and MMP2 related syndromes in a novel "defective collagenremodelling spectrum (DECORS)". In our opinion, this revised nosology better reflects the central role for impaired collagen remodeling, a potential target for pharmaceutical intervention. K E Y W O R D SECM remodeling, MMP14, MMP2, podosomes, SH3PXD2B

show abstract

Section: Discussion and Reviewmentioning

confidence: 99%

Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling

Vos

Wong

Welting

et al. 2019

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…However, further dental manifestations, such as effects on tooth structures, have not been reported. To date, dental effects have not been reported in closely related vanishing bone diseases, such as multicentric osteolysis with nodulosis and arthropathy (MONA), associated with mutations in MMP-2 [81]. …”

Section: Discussionmentioning

confidence: 99%

Multiple essential MT1-MMP functions in tooth root formation, dentinogenesis, and tooth eruption

Snider

Wimer

et al. 2016

Matrix Biology

View full text Add to dashboard Cite

Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a transmembrane zinc-endopeptidase that breaks down extracellular matrix components, including several collagens, during tissue development and physiological remodeling. MT1-MMP-deficient mice (MT1-MMP−/−) feature severe defects in connective tissues, such as impaired growth, osteopenia, fibrosis, and conspicuous loss of molar tooth eruption and root formation. In order to define the functions of MT1-MMP during root formation and tooth eruption, we analyzed the development of teeth and surrounding tissues in the absence of MT1-MMP. In situ hybridization showed that MT1-MMP was widely expressed in cells associated with teeth and surrounding connective tissues during development. Multiple defects in dentoalveolar tissues were associated with loss of MT1-MMP. Root formation was inhibited by defective structure and function of Hertwig's epithelial root sheath (HERS). However, no defect was found in creation of the eruption pathway, suggesting that tooth eruption was hampered by lack of alveolar bone modeling/remodeling coincident with reduced periodontal ligament (PDL) formation and integration with the alveolar bone. Additionally, we identified a significant defect in dentin formation and mineralization associated with the loss of MT1-MMP. To segregate these multiple defects and trace their cellular origin, conditional ablation of MT1-MMP was performed in epithelia and mesenchyme. Mice featuring selective loss of MT1-MMP activity in the epithelium were indistinguishable from wild type mice, and importantly, featured a normal HERS structure and molar eruption. In contrast, selective knock-out of MT1-MMP in Osterix-expressing mesenchymal cells, including osteoblasts and odontoblasts, recapitulated major defects from the global knock-out including altered HERS structure, short roots, defective dentin formation and mineralization, and reduced alveolar bone formation, although molars were able to erupt. These data indicate that MT1-MMP activity in the dental mesenchyme, and not in epithelial-derived HERS, is essential for proper tooth root formation and eruption. In summary, our studies point to an indispensable role for MT1-MMP-mediated matrix remodeling in tooth eruption through effects on bone formation, soft tissue remodeling and organization of the follicle/PDL region.

show abstract

“…MCP‐3 is also reported to be a physiological substrate of MMP‐2 in arthritis . Interestingly, humans with genetic loss of MMP‐2 activity suffer from crippling arthritis and a spectrum of cardiovascular problems including congenital cardiac malformations, transposition of the great arteries, mitral valve prolapse, bicuspid aortic valve, and atrial and ventricular septal defects . The molecular mechanisms underlying these pathologies are unknown, leaving clinicians without effective treatments .…”

Section: Introductionmentioning

confidence: 99%

Identification of a Novel Heart–Liver Axis: Matrix Metalloproteinase‐2 Negatively Regulates Cardiac Secreted Phospholipase A ₂ to Modulate Lipid Metabolism and Inflammation in the Liver

Hernandez-Anzaldo

Berry

Brglez

et al. 2015

JAHA

View full text Add to dashboard Cite

BackgroundEndocrine functions of the heart have been well established. We investigated the hypothesis that cardiac secretion of a unique phospholipase A2 recently identified by our laboratory (cardiac secreted phospholipase A2 [sPLA 2]) establishes a heart–liver endocrine axis that is negatively regulated by matrix metalloproteinase‐2 (MMP‐2).Methods and ResultsIn Mmp2 −/− mice, cardiac (but not hepatic) sPLA 2 was elevated, leading to hepatic inflammation, immune cell infiltration, dysregulation of the sterol regulatory element binding protein‐2 and liver X receptor‐α pathways, abnormal transcriptional responses to dietary cholesterol, and elevated triglycerides in very low‐density lipoprotein and in the liver. Expression of monocyte chemoattractant protein‐3, a known MMP‐2 substrate, was elevated at both mRNA and protein levels in the heart. Functional studies including in vivo antibody neutralization identified cardiac monocyte chemoattractant protein 3 as a possible agonist of cardiac sPLA 2 secretion. Conversely, systemic sPLA 2 inhibition almost fully normalized the cardiohepatic phenotype without affecting monocyte chemoattractant protein‐3. Finally, wild‐type mice that received high‐performance liquid chromatography–isolated cardiac sPLA 2 from Mmp2 −/− donors developed a cardiohepatic gene expression profile similar to that of Mmp2 −/− mice.ConclusionsThese findings identified the novel MMP‐2/cardiac sPLA 2 pathway that endows the heart with important endocrine functions, including regulation of inflammation and lipid metabolism in the liver. Our findings could also help explain how MMP2 deficiency leads to cardiac problems, inflammation, and metabolic dysregulation in patients.

show abstract

Multicentric osteolysis with nodulosis and arthropathy (MONA) with cardiac malformation, mimicking polyarticular juvenile idiopathic arthritis: case report and literature review

Abstract: The case documents the natural history of MONA and establishes a link between MMP2 deficiency and heart development, and given the recurring cardiac association, we suggest that all MONA patients be examined for possible cardiac defects.

Cited by 26 publications

References 16 publications

Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling

Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling

Multiple essential MT1-MMP functions in tooth root formation, dentinogenesis, and tooth eruption

Identification of a Novel Heart–Liver Axis: Matrix Metalloproteinase‐2 Negatively Regulates Cardiac Secreted Phospholipase A ₂ to Modulate Lipid Metabolism and Inflammation in the Liver

Contact Info

Product

Resources

About

Multicentric osteolysis with nodulosis and arthropathy (MONA) with cardiac malformation, mimicking polyarticular juvenile idiopathic arthritis: case report and literature review

Abstract: The case documents the natural history of MONA and establishes a link between MMP2 deficiency and heart development, and given the recurring cardiac association, we suggest that all MONA patients be examined for possible cardiac defects.

Cited by 26 publications

References 16 publications

Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling

Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling

Multiple essential MT1-MMP functions in tooth root formation, dentinogenesis, and tooth eruption

Identification of a Novel Heart–Liver Axis: Matrix Metalloproteinase‐2 Negatively Regulates Cardiac Secreted Phospholipase A 2 to Modulate Lipid Metabolism and Inflammation in the Liver

Contact Info

Product

Resources

About

Identification of a Novel Heart–Liver Axis: Matrix Metalloproteinase‐2 Negatively Regulates Cardiac Secreted Phospholipase A ₂ to Modulate Lipid Metabolism and Inflammation in the Liver