In Vivo Investigation of the Ameliorating Effect of Tempol against MIA-Induced Knee Osteoarthritis in Rats: Involvement of TGF-β1/SMAD3/NOX4 Cue

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 iodoace...

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Autores principales:	Hagar B. Abo-zalam, Rania M. Abdelsalam, Rehab F. Abdel-Rahman, Mohamed F. Abd-Ellah, Mahmoud M. Khattab
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	osteoarthritis monosodium iodoacetate tempol NOX4 Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/5b120a46e12840b49c9a7c5d3ccb22fe
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spelling	oai:doaj.org-article:5b120a46e12840b49c9a7c5d3ccb22fe2021-11-25T18:28:59ZIn Vivo Investigation of the Ameliorating Effect of Tempol against MIA-Induced Knee Osteoarthritis in Rats: Involvement of TGF-β1/SMAD3/NOX4 Cue10.3390/molecules262269931420-3049https://doaj.org/article/5b120a46e12840b49c9a7c5d3ccb22fe2021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6993https://doaj.org/toc/1420-3049Osteoarthritis (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. Moreover, it subsided the knee joint swelling. Tempol decreased the cartilage degradation-related biomarkers as matrix metalloproteinase-13, bone alkaline phosphatase (bone ALP), 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 transforming growth factor-β1 (TGF-β1). Tempol decreased the expression of chemokine (C-C motif) ligand 2 (CCL2). On the molecular level, tempol reduced the phosphorylated protein levels of p38 mitogen-activated protein kinase (MAPK), 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, and NOX4/p38MAPK/NF-κB and therefore modulation of oxidative stress, catabolic inflammatory cascades, chondrocyte metabolic homeostasis.Hagar B. Abo-zalamRania M. AbdelsalamRehab F. Abdel-RahmanMohamed F. Abd-EllahMahmoud M. KhattabMDPI AGarticleosteoarthritismonosodium iodoacetatetempolNOX4Organic chemistryQD241-441ENMolecules, Vol 26, Iss 6993, p 6993 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	osteoarthritis monosodium iodoacetate tempol NOX4 Organic chemistry QD241-441
spellingShingle	osteoarthritis monosodium iodoacetate tempol NOX4 Organic chemistry QD241-441 Hagar B. Abo-zalam Rania M. Abdelsalam Rehab F. Abdel-Rahman Mohamed F. Abd-Ellah Mahmoud M. Khattab In Vivo Investigation of the Ameliorating Effect of Tempol against MIA-Induced Knee Osteoarthritis in Rats: Involvement of TGF-β1/SMAD3/NOX4 Cue
description	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. Moreover, it subsided the knee joint swelling. Tempol decreased the cartilage degradation-related biomarkers as matrix metalloproteinase-13, bone alkaline phosphatase (bone ALP), 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 transforming growth factor-β1 (TGF-β1). Tempol decreased the expression of chemokine (C-C motif) ligand 2 (CCL2). On the molecular level, tempol reduced the phosphorylated protein levels of p38 mitogen-activated protein kinase (MAPK), 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, and NOX4/p38MAPK/NF-κB and therefore modulation of oxidative stress, catabolic inflammatory cascades, chondrocyte metabolic homeostasis.
format	article
author	Hagar B. Abo-zalam Rania M. Abdelsalam Rehab F. Abdel-Rahman Mohamed F. Abd-Ellah Mahmoud M. Khattab
author_facet	Hagar B. Abo-zalam Rania M. Abdelsalam Rehab F. Abdel-Rahman Mohamed F. Abd-Ellah Mahmoud M. Khattab
author_sort	Hagar B. Abo-zalam
title	In Vivo Investigation of the Ameliorating Effect of Tempol against MIA-Induced Knee Osteoarthritis in Rats: Involvement of TGF-β1/SMAD3/NOX4 Cue
title_short	In Vivo Investigation of the Ameliorating Effect of Tempol against MIA-Induced Knee Osteoarthritis in Rats: Involvement of TGF-β1/SMAD3/NOX4 Cue
title_full	In Vivo Investigation of the Ameliorating Effect of Tempol against MIA-Induced Knee Osteoarthritis in Rats: Involvement of TGF-β1/SMAD3/NOX4 Cue
title_fullStr	In Vivo Investigation of the Ameliorating Effect of Tempol against MIA-Induced Knee Osteoarthritis in Rats: Involvement of TGF-β1/SMAD3/NOX4 Cue
title_full_unstemmed	In Vivo Investigation of the Ameliorating Effect of Tempol against MIA-Induced Knee Osteoarthritis in Rats: Involvement of TGF-β1/SMAD3/NOX4 Cue
title_sort	in vivo investigation of the ameliorating effect of tempol against mia-induced knee osteoarthritis in rats: involvement of tgf-β1/smad3/nox4 cue
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5b120a46e12840b49c9a7c5d3ccb22fe
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In Vivo Investigation of the Ameliorating Effect of Tempol against MIA-Induced Knee Osteoarthritis in Rats: Involvement of TGF-β1/SMAD3/NOX4 Cue

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