Effects of TGF-β1 and IL-1β on expression of ADAMTS enzymes and TIMP-3 in human intervertebral disc degeneration

Wang,Shi-Long; Yu,Yong-Lin; Tang,Chao-Liang; Lv,Fei-Zhou

doi:10.3892/etm.2013.1348

Effects of TGF-β1 and IL-1β on expression of ADAMTS enzymes and TIMP-3 in human intervertebral disc degeneration

Authors:
- Shi-Long Wang
- Yong-Lin Yu
- Chao-Liang Tang
- Fei-Zhou Lv
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Affiliations: Department of Orthopedics, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, P.R. China
Published online on: October 15, 2013 https://doi.org/10.3892/etm.2013.1348
Pages: 1522-1526

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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% CO2 incubator. 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.

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