The Antioxidant tempol delays the MIA-induced osteoarthritis progression in rats via modulation of signaling pathways involving TGF-β1/SMAD3/NOX4 axis

Osteoarthritis (OA) is a complex disease characterized by structural, functional, and metabolic deteriorations of the whole joint and periarticular tissues. In the current study, we aimed to investigate the possible effects of tempol on knee OA induced by the chemical chondrotoxic monosodium iodoacetate (MIA) which closely mimics both the pain and structural changes associated with human OA. Rats were administrated oral tempol (100 mg/kg) one week post-MIA injection (3 mg/ 50 μL saline) at the right knee joints for 21 consecutive days. Tempol improved motor performance and debilitated the MIA-related radiological and histological alterations. Besides, it subsided the knee joint swelling. Tempol decreased the cartilage degradation-related biomarkers as matrix metalloproteinase-13, cartilage oligomeric matrix protein, and fibulin-3. The superoxide dismutase mimetic effect of tempol was accompanied by decreased NADPH oxidase 4 (NOX4), inflammatory mediators, nuclear factor kappa-B (NF-κB), over-released insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1). Tempol decreased the expression of chemotactic cytokine ligand 2 (CCL2), dickkopf‑related protein-1 (DKK-1), and protein kinase C (PKC). On the molecular level, tempol reduced the phosphorylated protein levels of p38 mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), and small mother against decapentaplegic 3 homologs (SMAD3). These findings suggest the promising role of tempol in ameliorating MIA-induced knee OA in rats via collateral suppression of the catabolic signaling cascades including TGF-β1/SMAD3/NOX4, NOX4/p38MAPK/NF-κB, and PI3K/Akt/NF-κB and therefore modulation of oxidative stress, catabolic inflammatory cascades, chondrocyte metabolic homeostasis, autophagy, and cell survival.

• Publication year

  2021

• Venue

  Unknown venue

• Publication date

  2021-05-12

• Fields of study

  Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.21203/RS.3.RS-499700/V1
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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