Table 1.

Main extracellular matrix components of a young and healthy IVD.

name	distribution/localization	putative/possible function
collagens
fibril-forming collagens
type I	AF and NP	confers tensile stiffness allowing torsion and flexion [27–30]
type II	AF and NP	confines PG within the matrix to retain more water to allow larger deformations and withstand greater compressive loads [31,32]
type III	NP and outer AF	organizes pericellular environment; allows extensibility of tissue [33–35]
type V	AF and NP (increased in AF cells when compared to NP cells)	regulates fibril diameter (smaller if this collagen is more abundant) influencing mechanical properties [35,36]
type XI [37]	all over, mostly NP	regulates fibril diameter (smaller if this collagen is more abundant) influencing mechanical properties [35,38]
beaded-filament forming collagens
type VI	all over, mostly NP	helps cell fixation to the matrix and facilitates collagen bundles' sliding and lubrication [39,40]
FACIT collagens
type IX	NP	maintains matrix integrity [41,42]
type XII	AF	might regulate fibrillogenesis [29,43]
type XIV	AF	might regulate fibrillogenesis [29,43]
proteoglycans
aggregating PGs
aggrecan	AF and NP	maintains IVD's osmotic pressure; may act as an anti-angiogenic factor due to its inhibition of endothelial cell migration [40,44,45]
versican	all over, mostly AF	favours the attachment of adjacent lamellae, contributes to resistance to compressive forces and facilitates cell migration, since it is an anti-adhesive molecule [35,40]
non-aggregating PGs
small leucine-rich proteoglycans (SLRPs)
decorin	outer AF and fibrillar NP	regulates collagen fibril diameter and spacing, maintaining uniform patterning; GFs' reservoir (TGF-β), modulating ECM metabolism [46–48]
biglycan	outer AF and NP (fibrillar and pericellular region)	GFs' reservoir (TGF-β), modulating ECM metabolism [46,47]
asporin	outer and inner AF, rarely NP	GFs' reservoir (TGF-β), modulating ECM metabolism; may play a major role in modulating chondrocyte matrix homeostasis [49,50]
fibromodulin	AF and NP	regulates collagen fibril diameter and spacing, maintaining uniform patterning; GFs' reservoir (TGF-β), modulating ECM metabolism [44,47]
lumican	AF and NP	regulates collagen fibril diameter and spacing, maintaining uniform patterning [44,51]
prolargin (encoded by PRELP*)	all over, mostly AF	anchors basement membranes to the underlying connective tissue [44,52]
chondroadherin	AF and NP	binds integrin ad collagen; regulates cell metabolism and ECM structure, promoting matrix homeostasis [44,53,54]
osteoglycin/mimecan	AF and NP	unknown [44]
other matrix proteins
other PGs
perlecan	AF and NP	has a role in cell proliferation and differentiation by acting as co-receptor for FGFs; matrix organization and stabilization; role in FGF signalling [40,55]
fibronectin	all over the disc	preserves structural integrity of the ECM; involved in cell adhesion through interaction with integrins [56–58]
elastin	all over the disc	preserves structural integrity of the ECM; helps to regain disc height and shape after deformation [59–61]
COMP	all over, mostly AF	preserves structural integrity of the ECM; binds other matrix proteins and catalyses polymerization of type II collagen fibrils; prevents vascularization of cartilage [62,63]
thrombospondin	AF	preserves structural integrity of the ECM; mediates cell adhesion, matrix–matrix interactions, cell migration and proliferation in other tissues; might prevent vascularization of the tissue; activates TGF-β complex [64,65]