Growth and Differentiation Factor-5 (GDF-5) in the Human Intervertebral Annulus Cells and Its Modulation by IL-1ß and TNF-α in Vitro

Growth and differentiation factor-5 (GDF-5) is a member of the TGF-ß superfamily which regulates cell division and differentiation. GDF-5 attracted high interest because of its role in skeletal development, especially in cartilaginous sites. Little is known, however, about the role of GFD-5 in disc cell biology. The present work demonstrated the immunohistologic presence of GDF-5 in human outer and inner annulus tissue. Microarray analysis of annulus cells showed significant upregulation of GDF-5 expression in herniated vs. non-herniatedlumbar discs (2.14fold change, p=0.021). In vitro three-dimensional culture studies challenged human annulus cells with IL-1ß and TNF-α, two proinflammatory cytokines known to be elevated in the human degenerating disc. Exposure resulted in significant downregulation of GDF-5 during both TNF-α exposure (5.83 fold change, p=0.044) and IL-1ß exposure (3.38 fold change, p=0.015). In vitro findings suggest that the degenerating discmilieu, with high proinflammatory cytokine levels, may limit expression of GDF-5, resulting in limited regenerative capacity of the intact disc.

Copyright © 2014. Published by Elsevier Inc.

KEYWORDS:

disc herniation, growth and differentiation factor-5, interleukin-1ß, intervertebral disc, proinflammatory cytokines, tumor necrosis factor-α

PMID:

 

24582800

 

[PubMed - as supplied by publisher]