title: Effects of TGF-β1 and IL-1β on expression of ADAMTS enzymes and TIMP-3 in human intervertebral disc degeneration.
abstract: The aim of this study was to investigate the effects of transforming growth factor-β1 (TGF-β1) and interleukin-1β (IL-1β) on the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) enzymes and their inhibitor, tissue inhibitor of metalloproteinase 3 (TIMP-3), in human intervertebral disc (IVD) degeneration. Cells from patients with IVD degeneration were cultured with Dulbecco's modified Eagle's medium with Ham's F12 nutrient mixture (DMEM/F12) medium at 37°C in a 5% CO2incubator. Cell proliferation was measured by cell counting kit-8 assays with varying concentrations of TGF-β1 and IL-1β in a time-response experiment. The mRNA and protein expression levels of ADAMTS-4, ADAMTS-5 and TIMP-3 were detected with qPCR and western blot analysis, respectively. The present study demonstrated that TGF-β1 promoted nucleus pulposus (NP) cell proliferation, decreased the expression of ADAMTS-4 and -5 and increased the expression of TIMP-3. By contrast, the IL-1β treatment inhibited NP cell proliferation and significantly increased the expression of ADAMTS-4 and -5. However, IL-1β appeared to have no marked effect on the expression of TIMP-3. This study suggests that TGF-β1 and IL-1β are involved in the synthesis and degradation of the extracellular matrix and may act as potential therapeutic targets for the prevention or reversal of IVD degeneration.
authors.affiliation: Department of Orthopedics, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, P.R. China.
authors.forename: Shi-Long
authors.initials: SL
authors.lastname: Wang
authors.forename: Yong-Lin
authors.initials: YL
authors.lastname: Yu
authors.forename: Chao-Liang
authors.initials: CL
authors.lastname: Tang
authors.forename: Fei-Zhou
authors.initials: FZ
authors.lastname: Lv
keywords: a disintegrin and metalloproteinase with thrombospondin motifs; interleukin-1β; nucleus pulposus; tissue inhibitor of metalloproteinase 3; transforming growth factor-β1