OBJECTIVE: The present paper aimed to investigate the therapeutic effect of quercetin in a rat model of bone cancer pain, and to further explore the molecular mechanism of quercetin in the treatment of bone cancer pain. METHODS: The activation status of the osteoblasts in each group of rats was detected by anti-tartaric acid phosphatase (TRAP) immunohistochemistry, while the activation status of the osteoclasts was detected by alkaline phosphatase (BAP) immunohistochemistry. An ELISA assay was used to detect the levels of serum type I collagen carboxy-terminal pro-peptide (CDC), tartrate-resistant acid phosphatase (TRAP5b), and osteocalcin in each group, as well as the expressions of the main inflammatory mediator membrane protease (trypsin), TNF-α, and IL-1β in the PAR2/TRPV1 pathway in serum. Taking CD68 as a marker, immunohistochemistry was used to detect the positive proportion of macrophages in the left tibia of each group. Western blot was applied to analyze the expressions of the RANKL, OPG, RANK, PTHrP and IGF-1 proteins in rat bone tissue, the inflammatory mediators IL-8, M-CSF and TNF-α, and the PAR2/TRPV1 pathway-related molecules PAR2, TRPV1, PKC-Y and PKA in rat DRG neurons, as well as the neurotransmitters c-Fos, GFAP, PKR, and CGRP in the spinal cord. RESULTS: Quercetin significantly reduces serum CTX, TRAP and osteocalcin expressions in a rat model of bone cancer pain and also significantly reduces the proportion of TRAP-positive cells. The drug can significantly reduce the positive proportion of local bone tissue macrophages in rats with bone cancer pain. It can significantly decrease the expressions of RANKL, RANK, PTHrP and IGF-1 proteins and the inflammatory mediators such as IL-8, M-CSF and TNF-α, significantly increase the expressions of OPG and further significantly inhibit the expressions of the PAR2/TRPV1 pathway-related molecules PAR2, TRPV1, PKC-γ and PKA in DRG neurons, as well as significantly reduce the levels of major inflammatory mediators (trypsin), TNF-α, and IL-1β in the PAR2/TRPV1 pathway. CONCLUSION: Quercetin can inhibit osteoclast activation and reduce bone destruction in the bone cancer pain model by regulating the RANKL/RANK/OPG signaling pathway and the inflammatory response. It can inhibit peripheral sensitization and central sensitization in bone cancer pain by regulating the PAR2/TRPV1 signaling pathway. IJCEP
OBJECTIVE: The present paper aimed to investigate the therapeutic effect of quercetin in a rat model of bone cancer pain, and to further explore the molecular mechanism of quercetin in the treatment of bone cancer pain. METHODS: The activation status of the osteoblasts in each group of rats was detected by anti-tartaric acid phosphatase (TRAP) immunohistochemistry, while the activation status of the osteoclasts was detected by alkaline phosphatase (BAP) immunohistochemistry. An ELISA assay was used to detect the levels of serum type I collagen carboxy-terminal pro-peptide (CDC), tartrate-resistant acid phosphatase (TRAP5b), and osteocalcin in each group, as well as the expressions of the main inflammatory mediator membrane protease (trypsin), TNF-α, and IL-1β in the PAR2/TRPV1 pathway in serum. Taking CD68 as a marker, immunohistochemistry was used to detect the positive proportion of macrophages in the left tibia of each group. Western blot was applied to analyze the expressions of the RANKL, OPG, RANK, PTHrP and IGF-1 proteins in rat bone tissue, the inflammatory mediators IL-8, M-CSF and TNF-α, and the PAR2/TRPV1 pathway-related molecules PAR2, TRPV1, PKC-Y and PKA in rat DRG neurons, as well as the neurotransmitters c-Fos, GFAP, PKR, and CGRP in the spinal cord. RESULTS:Quercetin significantly reduces serum CTX, TRAP and osteocalcin expressions in a rat model of bone cancer pain and also significantly reduces the proportion of TRAP-positive cells. The drug can significantly reduce the positive proportion of local bone tissue macrophages in rats with bone cancer pain. It can significantly decrease the expressions of RANKL, RANK, PTHrP and IGF-1 proteins and the inflammatory mediators such as IL-8, M-CSF and TNF-α, significantly increase the expressions of OPG and further significantly inhibit the expressions of the PAR2/TRPV1 pathway-related molecules PAR2, TRPV1, PKC-γ and PKA in DRG neurons, as well as significantly reduce the levels of major inflammatory mediators (trypsin), TNF-α, and IL-1β in the PAR2/TRPV1 pathway. CONCLUSION:Quercetin can inhibit osteoclast activation and reduce bone destruction in the bone cancer pain model by regulating the RANKL/RANK/OPG signaling pathway and the inflammatory response. It can inhibit peripheral sensitization and central sensitization in bone cancer pain by regulating the PAR2/TRPV1 signaling pathway. IJCEP
Authors: Jean Bousquet; Wienczyslawa Czarlewski; Torsten Zuberbier; Joaquim Mullol; Hubert Blain; Jean-Paul Cristol; Rafael De La Torre; Nieves Pizarro Lozano; Vincent Le Moing; Anna Bedbrook; Ioana Agache; Cezmi A Akdis; G Walter Canonica; Alvaro A Cruz; Alessandro Fiocchi; Joao A Fonseca; Susana Fonseca; Bilun Gemicioğlu; Tari Haahtela; Guido Iaccarino; Juan Carlos Ivancevich; Marek Jutel; Ludger Klimek; Helga Kraxner; Piotr Kuna; Désirée E Larenas-Linnemann; Adrian Martineau; Erik Melén; Yoshitaka Okamoto; Nikolaos G Papadopoulos; Oliver Pfaar; Frederico S Regateiro; Jacques Reynes; Yves Rolland; Philip W Rouadi; Boleslaw Samolinski; Aziz Sheikh; Sanna Toppila-Salmi; Arunas Valiulis; Hak-Jong Choi; Hyun Ju Kim; Josep M Anto Journal: Int Arch Allergy Immunol Date: 2021-02-10 Impact factor: 2.749