The response of foetal annulus fibrosus cells to growth factors: modulation of matrix synthesis by TGF-β1 and IGF-1

Abstract

The annulus fibrosus of the intervertebral disc is a complex radial-ply tissue that derives initially from segmental condensations of axial mesenchyme surrounding the notochord. These mesenchymal condensations differentiate into the early annulus fibrosus during foetal development-their outer part becoming fibrous, containing collagen type I; and their inner part cartilaginous, containing type II collagen and aggrecan. With post-natal growth and ageing, there is a switch from type I to type II collagen and an increase in proteoglycan synthesis in the outer annulus. This fibrocartilaginous metaplasia appears to occur in response to compressive loading of the tissue as occurs in tendons that wrap around bony pulleys, and driven by growth factors, such as TGF-β. In this study, using high-density micromass cultures, we have assessed the response of foetal outer annulus cells to growth factor stimulation with TGF-β1 and IGF-1, growth factors known to occur within the developing disc. We qualitatively and quantitatively describe the stimulatory effects of these growth factors, both alone and in combination, on the synthesis of sulphated glycosaminoglycan, and collagen types I and II by annulus cells. We show a potential role for TGF-β1 in pushing cells towards a fibrocartilaginous phenotype, with possible complementary effects of IGF-1.

Resveratrol-Mediated Reduction of Collagen by Inhibiting Proliferation and Producing Apoptosis in Human Hypertrophic Scar Fibroblasts

“…44) Some reports have proposed a role for TGF-1 and insulin-like growth factor I (IGF-I) in mediating abnormal cell proliferation and increasing synthesis of ECM or collagen, 45,46) and the estrogen receptor antagonist ICI 182780 can partly reverse resveratrol-induced inhibitory effects on AGEs-mediated cell proliferation and prolyl hydroxylase activity. Another study found that resveratrol caused cellcycle arrest and decreased the expression of procollagen types I and III mRNA in rat smooth muscle cells, and that this was associated with attenuation of the stimulatory effects of TGF-1 and IGF-I on cell proliferation and collagen production.…”

Implications for a Stem Cell Regenerative Medicine Based Approach to Human Intervertebral Disk Degeneration

“…This demarcation between IAF and OAF become less pronounced at later stages of development and in the adult. (Hayes and Ralphs, 2011). The fact that the entire spine research field has so far been unsuccessful in generating true AF and NP cells from MSCs suggests that they might not be the ideal starting material despite their relative ease of isolation and autologous nature.…”

Recent progress in histochemistry and cell biology

“…This also applies to insulin-like growth factor (IGFs) family members. In their study, Hayes and Ralphs (2011) investigated the fibroblastic-to-cartilaginous change in fetal outer annulus cells, applying growth factor stimulation with TGF-b1 and IGF-1, to detect synthesis of sulphated GAGs and collagen types I and II. Using E19 rat embryo IVDs as a source of fetal outer annulus cells, the authors could demonstrate the capacity of such cells to be able to recapitulate changes in ECM composition that normally occur during the fibroblastic-to-cartilaginous switch of the outer annulus during its growth and aging, with TGF-b1 playing a key role in this process and IGF-1 carrying out synergistic effects.…”