Cell News 3/2013
16
RESEARCH NEWS
The cartilage extracellular matrix and its role in disease
Frank Zaucke
Center for Biochemistry, University of Cologne, 50931 Cologne, Germany
Supramolecular assembly in the cartilage matrix
In cartilage, the extracellular matrix (ECM) occupies the ma-
jor volume fraction of the tissue and is responsible for its main
functions. At the articular surface the ECM is involved in load
bearing and allowing smooth articulation. In the growth plate
the ECM is crucial for the process of endochondral ossification
and proper development of long bones. At the molecular level
these functions are carried out mainly by two supramolecular
compartments, the collagen-containing fibrillar network and
the extrafibrillar matrix, which is comprised mainly of the large,
cartilage-specific proteoglycan aggrecan (Fig. 1).
In order to warrant tissue stability, a mutual interaction between
cartilage fibrils and the extrafibrillar matrix is required. Cartila-
ge fibrils are protein complexes containing at least collagens II
and XI and, optionally, collagen IX (Bruckner, 2010). Collagen IX
stabilizes thin, prototypic cartilage fibrils preferentially found in
the territorial matrix as baskets around chondrocytes (Hagg et
al., 1988). It forms a macromolecular alloy together with colla-
gens II and XI, but also projects its amino terminal domains COL3
and NC4 away from the surface into the fibril-proximal environ-
ment which allows interactions with other adaptor proteins or
the aggrecan matrix (Vaughan et al., 1988). In addition, some
fibril populations are associated with small leucine-rich proteo-
glycans, like decorin, biglycan, fibromodulin and chondroadherin
(Kalamajski & Oldberg, 2010). Further, matrilins, cartilage oligo-
meric matrix protein (COMP) and most likely more proteins that
are neither collagens nor proteoglycans are present. Thus, the
fibril surface is densely populated with several types of molecu-
les (Fig. 1).
Perifibrillar proteins
The molecular nature of the fibrillar periphery is of substantial
interest and the cartilage matrix components present here are
likely to be of particular biological importance. The literature and
our own previous studies underline the importance of the inter-
actions of and among these adaptor proteins: COMP interacts
with collagens I and II (Rosenberg et al., 1998) and via its glo-
bular C-terminal domain with the non-collagenous domains of
collagen IX (Pihlajamaa et al., 2004; Spitznagel et al., 2004; Thur
et al., 2001). In addition, binding of COMP to the major cartila-
ge proteoglycan aggrecan has been demonstrated (Chen et al.,
2007). Matrilin-3 binds to the fibrillar collagens II and XI (Otten
et al., 2010) and, most likely via its A-domain, to the collagenous
domains of collagen IX (Budde et al., 2005). Matrilin-3 can form
heterooligomers with matrilin-1 (Klatt et al., 2011) that in turn
has been shown to interact directly with aggrecan (Hauser et
al., 1996). The exact localization of some perifibrillar proteins
was analysed by immunogold labelling in isolated native sup-
rastructures from chondrosarcoma tissue (Wiberg et al., 2003).
In this study, the composition and spatial organization of supra-
molecular assemblies was characterized by electron microscopy
Figure 1. Alcian blue stained paraffin section of a tibia from a 1 month old mouse and simplified model of the supramolecular assembly in the
cartilage extracellular matrix
(A) Cartilage tissue is stained in blue. Articular and growth plate cartilage is indicated by a box. (B) Perifibrillar proteins like matrilin-1/-3 (red), COMP
(blue) and collagen IX (green) act as adaptor molecules to interconnect banded collagen fibrils with each other and/or with collagen VI beaded filaments
to generate a heterotypic fibrillar network. More details in the text. Modfied from Budde et al., 2005.
