Collagen fibrillogenesis in the development of the annulus fibrosus of the intervertebral disc

Abstract

The annulus fi brosus of the intervertebral disc is a complex, radial-ply connective tissue consisting of concentric lamellae of oriented collagen. Whilst much is known of the structure of the mature annulus, less is known of how its complex collagenous architecture becomes established; an understanding of which could inform future repair/ regenerative strategies. Here, using a rat disc developmental series, we describe events in the establishment of the collagenous framework of the annulus at light and electron microscopic levels and examine the involvement of class I and II small leucine rich proteoglycans (SLRPs) in the matrix assembly process. We show that a period of sustained, ordered matrix deposition follows the initial cellular differentiation/orientation phase within the foetal disc. Fibrillar matrix is deposited from recesses within the plasma membrane into compartments of interstitial space within the outer annulus -the orientation of the secreted collagen refl ecting the initial cellular orientation of the laminae. Medially, we demonstrate the development of a reinforcing 'cage' of collagen fi bre bundles around the foetal nucleus pulpous. This derives from the fusion of collagen bundles between presumptive end-plate and inner annulus. By birth, the distinct collagenous architectures are established and the disc undergoes considerable enlargement to maturity. We show that fi bromodulin plays a prominent role in foetal development of the annulus and its attachment to vertebral bodies. With the exception of keratocan, the other SLRPs appear associated more with cartilage development within the vertebral column, but all become more prominent within the disc during its growth and differentiation.

Meniscus, articular cartilage and nucleus pulposus: a comparative review of cartilage-like tissues in anatomy, development and function

“…The notochord’s transition into the NP, as well as the direction of other mesenchymal cell populations during development, is controlled through Brachyury (T), Sonic hedgehog (Shh), Noggin (Nog), transforming growth factor beta (TGFβ), and other signaling molecules (Chan et al , 2014). The Shh-dependent expression of Paired box 1 and 9 (Pax1/9) synergistically regulate vertebral column development (Peters et al ., 1999), whereas TGFβ is involved in the differentiation of the sclerotome into AF cells (Hayes et al , 2011). …”

Ageing in the musculoskeletal system

“…The ECM of the AF is organized into 15–25 concentric lamellae oriented at 65° relative to the vertical plane (Hayes et al. 2011). These lamellae are interconnected by PG aggregates, elastin and lubricin, and also type-VI collagen fibers (Melrose et al.…”

Bridging the Gap: Understanding Embryonic Interverterbal Disc Development

“…It is noteworthy that such distinct features of inner and outer annulus fibrosus are visible only at embryonic stages and that in the adult IVDs the annulus fibrosus is uniformly fibrous [71]. The reasons for such distinction at an embryonic stage and how it is resolved in the adult stage remains to be identified.…”

“…Also, Fibromodulin (Fmod), an IVD marker, was proven to be a downstream target of TGF-β signaling. The authors thus proposed a potential role of TGF-β signaling in annulus fibrosus differentiation and prevention of chondrocyte differentiation in the IVD region [16,59,[69][70][71].…”