Autophagy and apoptosis are important in maintaining the metabolic homeostasis of intervertebral disc cells, and transforming growth factor-β1 (TGF-β1) is able to delay
intervertebral disc degeneration. This study determined the effect of TGF-β1 on the crosstalk between autophagy and apoptosis in the disc cells, with the aim to provide molecular mechanism support for the prevention and treatment of
disc degeneration. Annulus fibrosus (AF) cells were isolated and cultured under serum
starvation. 10 ng/mL TGF-β1 reduced the apoptosis incidence in the cells under serum
starvation for 48 h, down-regulated the autophagy incidence in the cells pretreated with
3-methyladenine (3-MA) or
Bafilomycin A (Baf A), partly rescued the increased apoptosis incidence in the cells pretreated with 3-MA, while further reduced the decreased apoptosis incidence in the cells pretreated with Baf A. Meanwhile, TGF-β1 down-regulated the expressions of autophagic and apoptotic markers in the cells under
starvation, partly down-regulated the expressions of
Beclin-1, LC3 II/I and cleaved
caspase-3 in the cells pretreated with 3-MA or Baf A, while significantly decreased the expression of Bax/Bcl-2 in the cells pretreated with Baf A. 3-MA blocked the phosphorylation of both AKT and mTOR and partly reduced the inhibitory effect of TGF-β1 on the expression of LC3 II/I and cleaved
caspase-3. TGF-β1 enhanced the expression of p-ERK1/2 and down-regulated the expressions of LC3 II/I and cleaved
caspase-3.
U0126 partly reversed this inhibitory effect of TGF-β1. In conclusion, TGF-β1 protected against apoptosis of AF cells under
starvation through down-regulating excessive autophagy. PI3K-AKT-mTOR and MAPK-ERK1/2 were the possible signaling pathways involved in this process.