Unexpected matrix diseases and novel therapeutic strategies

Claudia Nicolae, Bjorn R. Olsen

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

Within the framework of a broad definition of the extracellular matrix (ECM), this review discusses three genetic disorders in which major pathogenetic features have been traced back to alterations in the levels/activities of matrix components. In each case, disease-associated alterations are found both intra- and extracellularly. The nature of the ECM involvement is surprising, offers an exciting therapeutic opportunity, and deepens our understanding of ECM-cell interactions. The first of these disorders, cherubism, is a case of inflammatory bone loss in the jaws of children for reasons that are surprisingly systemic in nature, considering the local nature of the disease. The primary defect involves an intracellular signaling molecule, but a major pathogenetic component and therapeutic target of the disease is the extracellular cytokine tumor necrosis factor alpha. The second disorder, Knobloch syndrome, is caused by recessive mutations in collagen XVIII. Although this protein has been classified as belonging to a group of structural macromolecules, the consequence of the mutations is impairment of cellular metabolism. The third disorder, infantile hemangioma, is a common tumor of capillary endothelial cells in infancy. The tumor appears within a few days/weeks after birth, grows rapidly over several months, and regresses over several years. The proliferative phase is the result of constitutively high levels of vascular endothelial cell growth factor (VEGF)-dependent signaling through VEGF receptor 2 (VEGFR2), but recent studies have led to the surprising conclusion that abnormalities in a cell-surface receptor complex controlling expression of the VEGF decoy receptor VEGFR1 is the underlying cause.

Original languageEnglish (US)
Pages (from-to)155-165
Number of pages11
JournalCell and Tissue Research
Volume339
Issue number1
DOIs
StatePublished - Jan 1 2010

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Extracellular Matrix
Vascular Endothelial Growth Factor Receptor
Cherubism
Collagen Type XVIII
Vascular Endothelial Growth Factor Receptor-2
Mutation
Inborn Genetic Diseases
Cell Surface Receptors
Hemangioma
Jaw
Cell Communication
Vascular Endothelial Growth Factor A
Neoplasms
Therapeutics
Endothelial Cells
Tumor Necrosis Factor-alpha
Parturition
Cytokines
Bone and Bones
Proteins

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Cell Biology
  • Histology

Cite this

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Unexpected matrix diseases and novel therapeutic strategies. / Nicolae, Claudia; Olsen, Bjorn R.

In: Cell and Tissue Research, Vol. 339, No. 1, 01.01.2010, p. 155-165.

Research output: Contribution to journalReview article

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