1. Academic Validation
  2. SND1 aggravates mitochondrial damage, apoptosis and extracellular matrix degradation in IL-1β-stimulated chondrocytes via PINK1/BECN1 pathway

SND1 aggravates mitochondrial damage, apoptosis and extracellular matrix degradation in IL-1β-stimulated chondrocytes via PINK1/BECN1 pathway

  • Eur J Med Res. 2023 Sep 25;28(1):371. doi: 10.1186/s40001-023-01340-y.
Shufeng Lin # 1 Huiyang Guo # 1 Xiaoxuan You 1 Zefeng Zhang 1 Hui Ye 2
Affiliations

Affiliations

  • 1 Department of Orthopedics, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China.
  • 2 Department of Orthopedics, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China. dryehuifmu@126.com.
  • # Contributed equally.
Abstract

Recently, evidence has suggested a regulatory role for SND1 in osteoarthritis progression. Interestingly, we found that SND1 protein expression was increased, mitochondria were shrunken and decreased in number, mitochondrial membrane potential was decreased, mitochondrial ROS production was increased, and ATP levels were decreased in IL-1β treated mouse chondrocytes, and SND1 silencing removed these changes. Furthermore, IL-1β treatment promoted inflammatory factor secretion in chondrocytes, promoted cell Apoptosis, increased MMP13 protein and inhibited collagen II protein expression, and si-SND1 inhibited the IL-1β effects. We validated the association between SND1 and PINK1 and found that PINK1 reversed the inhibitory effects of SND1 silencing on IL-1β-induced mitochondrial damage, inflammatory reaction, Apoptosis and extracellular matrix degradation in mouse chondrocytes. Furthermore, we found that PINK1 upregulated BECN1 protein expression and that BECN reversed the inhibitory effects of PINK1 silencing on IL-1β-induced mitochondrial damage, inflammatory reaction, Apoptosis and extracellular matrix degradation. Further mechanistic studies revealed that PINK1 inhibited the AMPK/mTOR signaling axis to aggravate IL-1β induced mouse chondrocytes injury by upregulating BECN1 protein expression. In vivo results showed that the damage to cartilage tissue was significantly alleviated in rats with osteoarthritis by knocking down SND1 expression.

Keywords

BECN1 pathway; Extracellular matrix; Mitochondrial; Osteoarthritis; SND1; The PINK1.

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