Journal
BIOTECHNOLOGY LETTERS
Volume 39, Issue 4, Pages 623-632Publisher
SPRINGER
DOI: 10.1007/s10529-016-2280-3
Keywords
Intervertebral disc degeneration; MicroRNA-15b; SMAD3; Nucleus pulposus; IL-1 beta; Extracellular matrix degradation
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Funding
- National Natural Science Foundation of China [81272025]
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Objectives To determine the role of microRNA-15b (miR-15b) in interleukin-1 beta (IL-1 beta)-induced extracellular matrix (ECM) degradation in the nucleus pulposus (NP). Results MiR-15b was up-regulated in degenerative NP tissues and in IL-1 beta-stimulated NP cells, as compared to the levels in normal controls (normal tissue specimens from patients with idiopathic scoliosis). Bioinformatics and luciferase activity analyses showed that mothers against decapentaplegic homolog 3 (SMAD3), a key mediator of the transforming growth factor-beta signaling pathway, was directly targeted by miR-15b. Functional analysis demonstrated that miR-15b overexpression aggravated IL-1 beta-induced ECM degradation in NP cells, while miR-15b inhibition had the opposite effects. Prevention of IL-1 beta-induced NP ECM degeneration by the miR-15b inhibitor was attenuated by small-interfering-RNA-mediated knockdown of SMAD3. In addition, activation of MAP kinase and nuclear factor-kappa B up-regulated miR-15b expression and down-regulated SMAD3 expression in IL-1 beta-stimulated NP cells. Conclusions MiR-15b contributes to ECM degradation in intervertebral disc degeneration (IDD) via targeting of SMAD3, thus providing a novel therapeutic target for IDD treatment.
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