Publication: Genetic mouse models for the functional
analysis of the perifibrillar components collagen IX,
COMP and matrilin-3: Implications for growth
cartilage differentiation and endochondral ossification
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Date
2009
Authors
Zaucke, Frank ; Grässel, Susanne
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
The mutual interaction of the two
supramolecular compartments, the fibrillar and
extrafibrillar matrix is a prerequisite for stability and
integrity of the cartilage extracellular matrix. The
fibrillar periphery, composed of collagen IX, matrilins
and cartilage oligomeric matrix protein (COMP) among
other components, constitutes the interface which
mediates interactions between the two compartments.
Mutations in these peripheral macromolecules cause a
broad spectrum of skeletal conditions such as pseudoachondroplasia (PSACH) and multiple epiphyseal
dysplasia (MED), which severely affect the organization
and integrity of the cartilage growth matrix in humans.
Transgenic and knockout mouse models for collagen IX,
matrilin-3 and COMP and combinations thereof display
cartilage abnormalities and pathologies of varying
severity. Absence of collagen IX appears to cause the
most severe growth plate phenotype with a profoundly
disturbed morphological organization affecting size and
shape of the long bones. Notably, similar growth plate
phenotypes, including irregularities in the proteoglycan
content, hypocellular central regions, disorganized
proliferation columns with atypically shaped and
oriented chondrocytes and alterations in the hypertrophic
zone are observed in transgenic mice lacking other
macromolecules or carrying mutations therein. These
include collagens II and XI, integrin subunits, integrin
linked kinase (ILK), HIF-1α, VEGFα and the tumor
suppressor PTEN. Notably, mutations in ciliar proteins
such as Kif3α, polaris or Smo/Gli severely affect the
ability of chondrocytes to move and to become arranged
in columns. Absence or mutational changes of a variety
of different, non-related cartilage macromolecules
apparently cause similar pathologies and abnormalities
of the growth cartilage, suggesting a limited number of
underlying molecular mechanisms
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