SDF-1α Promotes Chondrocyte Autophagy through CXCR4/mTOR Signaling Axis

• Published in: International journal of molecular sciences Vol. 24; no. 2; p. 1710
• Main Authors: Li, Jiazhou, Chen, Hao, Cai, Lang, Guo, Daimo, Zhang, Demao, Zhou, Xuedong, Xie, Jing
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15.01.2023; MDPI
• Subjects: Adenoviruses; Apoptosis; Assaying; Autophagy; Autophagy - genetics; Biological activity; Cartilage; Chemokine CXCL12 - metabolism; chondrocyte; Chondrocytes; Chondrocytes - metabolism; Chondrogenesis; CXCR4; CXCR4 protein; Cytokines; Gene expression; Genotype & phenotype; Harsh environments; Homeostasis; Immunofluorescence; mTOR; Phagosomes; Phosphorylation; Proteins; Quantitative analysis; Receptors, CXCR4 - metabolism; SDF-1 protein; SDF-1α; Signal Transduction; siRNA; TOR protein; TOR Serine-Threonine Kinases - metabolism; Transfection; Western blotting; SDF-1α; mTOR; CXCR4; autophagy; chondrocyte
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24021710

SDF-1α, the most common isoform of stromal cell-derived factor 1, has shown vital effects in regulating chondrocyte proliferation, maturation, and chondrogenesis. Autophagy is a highly conserved biological process to help chondrocytes survive in harsh environments. However, the effect of SDF-1α on chondrocyte autophagy is still unknown. This study aims to investigate the effect of SDF-1α on chondrocyte autophagy and the underlying biomechanism. Transmission electron microscope assays and mRFP-GFP-LC3 adenovirus double label transfection assays were performed to detect the autophagic flux of chondrocytes. Western blots and immunofluorescence staining assays were used to detect the expression of autophagy-related proteins in chondrocytes. RNA sequencing and qPCR were conducted to assess changes in autophagy-related mRNA expression. SDF-1α upregulated the number of autophagosomes and autolysosomes in chondrocytes. It also increased the expression of autophagy-related proteins including ULK-1, Beclin-1 and LC3B, and decreased the expression of p62, an autophagy substrate protein. SDF-1α-mediated autophagy of chondrocytes required the participation of receptor CXCR4. Moreover, SDF-1α-enhanced autophagy of chondrocytes was through the inhibition of phosphorylation of mTOR signaling on the upstream of autophagy. Knockdown by siRNA and inhibition by signaling inhibitor further confirmed the importance of the CXCR4/mTOR signaling axis in SDF-1α-induced autophagy of chondrocytes. For the first time, this study elucidated that SDF-1α promotes chondrocyte autophagy through the CXCR4/mTOR signaling axis.