Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1864, Issue 11, Pages 3754-3768Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2018.08.033
Keywords
Circular RNA SEMA4B (circSEMA4B); miR-431; Nucleus pulposus cells (NPCs); Intervertebral disc degeneration (IDD); Wnt signaling
Funding
- National Natural Science Foundation of China [81802211, 81871821]
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Intervertebral disc (IVD) degeneration (IDD), characterized by elevated levels of proinflammatory mediators, increased Aggrecan and collagen degradation, and increased degradation of extracellular matrix (ECM), has been widely regarded as a significant contributor to low back pain. Genetics are significant factors contribute to IDD. Based on previous data, circular RNA SEMA4B (circSEMA4B) is down-regulated in IDD specimens; herein, we demonstrated circSEMA4B overexpression could attenuate the effect of IL-1 beta on nucleus pulposus cell (NPC) proliferation, senescence, and ECM and Aggrecan degradation in IDD via Wnt signaling. Moreover, miR-431, a direct target of circSEMA4B, could bind to the 3'UTR of SERPI or GSK-3 beta, two inhibitory regulators of Wnt signaling, to inhibit their expression thus playing a role similar to the activator of Wnt signaling in NPCs. The effect of circSEMA4B knockdown on NPCs was partially reversed by miR-431 inhibition; circSEMA4B serves as a miR-431 sponge to compete with SERPI or GSK-313 for miR-431 binding, thus inhibiting IL-1 beta-induced degenerative process in NPCs through Wnt signaling. Rescuing circSEMA4B expression in NPCs in IDD might present a potential strategy for IDD improvement.
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