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

Abstract

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.

Exploring the Interplay of RUNX2 and CXCR4 in Melanoma Progression

“…Furthermore, it has been demonstrated that the CXCL12/CXCR4 axis promotes autophagy through the MiR-125b microRNA, which thus functions as an important downstream mediator upon the activation of the CXCL12/CXCR4 axis [ 42 ]. In addition, CXCL12 plays a significant role in the induction of autophagy in chondrocytes through the activation of the CXCR4/mTOR signalling axis [ 43 ]. In particular, accordingly to our data, the authors demonstrated that CXCR4 induces autophagy by reducing the phosphorylation level of mTOR [ 43 ].…”

“…In addition, CXCL12 plays a significant role in the induction of autophagy in chondrocytes through the activation of the CXCR4/mTOR signalling axis [ 43 ]. In particular, accordingly to our data, the authors demonstrated that CXCR4 induces autophagy by reducing the phosphorylation level of mTOR [ 43 ].…”

TGF‐β3 mediates mitochondrial dynamics through the p‐Smad3/AMPK pathway

“…And dynamin‐related protein 1 (Drp1), and fission 1 protein (Fis1) are among the essential proteins responsible for mitochondrial fission processes 19 . Recent reports have revealed significant advancements in mitochondrial dynamics through characterizing the key regulators involved in mitochondrial fusion and fission 20,21 . The Adenosine monophosphate‐activated protein kinase (AMPK) signalling plays significant roles in mitochondrial morphology 22 .…”

“… 19 Recent reports have revealed significant advancements in mitochondrial dynamics through characterizing the key regulators involved in mitochondrial fusion and fission. 20 , 21 The Adenosine monophosphate‐activated protein kinase (AMPK) signalling plays significant roles in mitochondrial morphology. 22 AMPK acts as a metabolic sensor, governing mitochondrial dynamics and maintaining energy balance.…”