FK506 Induces the TGF-β1/Smad 3 Pathway Independently of Calcineurin Inhibition to Prevent Intervertebral Disk Degeneration

• Main Authors: Jun Ge, Yingjie Wang, Qi Yan, Cenhao Wu, Hao Yu, Huilin Yang, Jun Zou
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-12-01
• Series: Frontiers in Cell and Developmental Biology
• Subjects: FK506; disk degeneration; TGFβ; Smad3; signal pathway
• Online Access: https://www.frontiersin.org/articles/10.3389/fcell.2020.608308/full

BackgroundIntervertebral disk (IVD) degeneration is the most common cause of lower back pain. Inhibiting inflammation is a key strategy for delaying IVD degeneration. Tacrolimus (FK506) is a potent immunosuppressive agent that is also beneficial to chondrocytes via alleviating inflammation. However, the potential function of FK506 in IVD and the underlying mechanisms remain unknown. The current study is aim at exploring the underlying mechanism of FK506 in preventing IVD degeneration.MethodsCell morphology was imaged using an optical microscope. mRNA levels of nucleus pulposus (NP) matrix components were determined by qRT-PCR, and protein expression NP matrix components was assessed by western blotting. A rat caudal IVD degeneration model was established to test for FK506 in vivo.ResultsFK506 improved the morphology of NP cells and the cell function at both the mRNA and protein level. FK506 could attenuate NP degeneration induced by IL-1β. Furthermore, FK506 exerted its function via TGFβ/Smad3 activation instead of through calcineurin inhibition. Inhibition of the TGF-β pathway prevented the protective effect of FK506 on IVD degeneration. In an in vivo study, FK506 injection reversed the development of rat caudal IVD degeneration influenced by Smad3.ConclusionOur current study demonstrates the positive effect of FK506 on delaying the degeneration of IVD via the TGFβ/Smad3 pathway.