title: Growth and differentiation factor-5 (GDF-5) in the human intervertebral annulus cells and its modulation by IL-1ß and TNF-α in vitro.
abstract: 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-herniated lumbar discs (2.14-fold 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 disc milieu, with high proinflammatory cytokine levels, may limit expression of GDF-5, resulting in limited regenerative capacity of the intact disc.
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, NC, USA. Electronic address: helen.gruber@carolinashealthcare.org.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Gruber
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, NC, USA.
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Hoelscher
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, NC, USA.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Ingram
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, NC, USA.
authors.forename: Synthia
authors.initials: S
authors.lastname: Bethea
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, NC, USA.
authors.forename: Edward N
authors.initials: EN
authors.lastname: Hanley
mesh_terms: D018929:Cell Culture Techniques; D005786:Gene Expression Regulation / Q000187:drug effects; D055428:Growth Differentiation Factor 5 / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D007403:Intervertebral Disc / Q000166:cytology / Q000378:metabolism; D007405:Intervertebral Disc Displacement / Q000235:genetics* / Q000473:pathology; D046228:Microarray Analysis; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D055428:Growth Differentiation Factor 5; D053583:Interleukin-1beta; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha
keywords: Disc herniation; Growth and differentiation factor-5; Interleukin-1ß; Intervertebral disc; Proinflammatory cytokines; Tumor necrosis factor-α