Regulation of calcitonin gene-related peptide expression through the COX-2/mPGES-1/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritis

Abstract Background The infrapatellar fat pad (IFP) is implicated in knee osteoarthritis (KOA). Calcitonin gene-related peptide (CGRP), a vasoactive neuropeptide expressed in joint tissues and synovial tissues (ST), was recently found to be associated with KOA progression and pain. CGRP is expressed...

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Main Authors: Jun Aikawa, Kentaro Uchida, Shotaro Takano, Gen Inoue, Dai Iwase, Masayuki Miyagi, Manabu Mukai, Shintaro Shoji, Hiroyuki Sekiguchi, Masashi Takaso
Format: Article
Language:English
Published: BMC 2018-09-01
Series:Lipids in Health and Disease
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12944-018-0864-8
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author Jun Aikawa
Kentaro Uchida
Shotaro Takano
Gen Inoue
Dai Iwase
Masayuki Miyagi
Manabu Mukai
Shintaro Shoji
Hiroyuki Sekiguchi
Masashi Takaso
author_facet Jun Aikawa
Kentaro Uchida
Shotaro Takano
Gen Inoue
Dai Iwase
Masayuki Miyagi
Manabu Mukai
Shintaro Shoji
Hiroyuki Sekiguchi
Masashi Takaso
author_sort Jun Aikawa
collection DOAJ
description Abstract Background The infrapatellar fat pad (IFP) is implicated in knee osteoarthritis (KOA). Calcitonin gene-related peptide (CGRP), a vasoactive neuropeptide expressed in joint tissues and synovial tissues (ST), was recently found to be associated with KOA progression and pain. CGRP is expressed in the IFPs of human KOA patients; however, its regulation has not been elucidated. Methods IFPs and STs were harvested from 138 KOA patients during total knee replacement (TKR) and analyzed for CGRP, cycloxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1) expression using real-time polymerase chain reaction (PCR). To investigate CGRP regulation by prostaglandin E2 (PGE2), adipocytes (Ad) and the stromal vascular fraction (SVF) were harvested from IFPs using collagenase. Synovial cells (SYC) were also harvested from ST and stimulated with vehicle (serum-free culture medium), PGE2, or CGRP. Results CGRP, COX-2, and mPGES-1 expression levels were significantly higher in IFPs than STs. PGE2 stimulation increased CGRP expression in Ad, the SVF, and SYC; however, CGRP expression was significantly higher in PGE2-stimulated SVF than PGE2-stimulated SYC. CGRP stimulation had no effect on COX-2 or mPGES-1 expression. Conclusions CGRP expression in the IFP of KOA patients is regulated by the COX-2/mPGES-1/PGE2 pathway.
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spelling doaj.art-eedc56747da549808655c05fab3c9ab52022-12-22T00:45:00ZengBMCLipids in Health and Disease1476-511X2018-09-011711610.1186/s12944-018-0864-8Regulation of calcitonin gene-related peptide expression through the COX-2/mPGES-1/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritisJun Aikawa0Kentaro Uchida1Shotaro Takano2Gen Inoue3Dai Iwase4Masayuki Miyagi5Manabu Mukai6Shintaro Shoji7Hiroyuki Sekiguchi8Masashi Takaso9Department of Orthopedic Surgery, Kitasato University School of MedicineDepartment of Orthopedic Surgery, Kitasato University School of MedicineDepartment of Orthopedic Surgery, Kitasato University School of MedicineDepartment of Orthopedic Surgery, Kitasato University School of MedicineDepartment of Orthopedic Surgery, Kitasato University School of MedicineDepartment of Orthopedic Surgery, Kitasato University School of MedicineDepartment of Orthopedic Surgery, Kitasato University School of MedicineDepartment of Orthopedic Surgery, Kitasato University School of MedicineShonan University of Medical Sciences Research InstituteDepartment of Orthopedic Surgery, Kitasato University School of MedicineAbstract Background The infrapatellar fat pad (IFP) is implicated in knee osteoarthritis (KOA). Calcitonin gene-related peptide (CGRP), a vasoactive neuropeptide expressed in joint tissues and synovial tissues (ST), was recently found to be associated with KOA progression and pain. CGRP is expressed in the IFPs of human KOA patients; however, its regulation has not been elucidated. Methods IFPs and STs were harvested from 138 KOA patients during total knee replacement (TKR) and analyzed for CGRP, cycloxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1) expression using real-time polymerase chain reaction (PCR). To investigate CGRP regulation by prostaglandin E2 (PGE2), adipocytes (Ad) and the stromal vascular fraction (SVF) were harvested from IFPs using collagenase. Synovial cells (SYC) were also harvested from ST and stimulated with vehicle (serum-free culture medium), PGE2, or CGRP. Results CGRP, COX-2, and mPGES-1 expression levels were significantly higher in IFPs than STs. PGE2 stimulation increased CGRP expression in Ad, the SVF, and SYC; however, CGRP expression was significantly higher in PGE2-stimulated SVF than PGE2-stimulated SYC. CGRP stimulation had no effect on COX-2 or mPGES-1 expression. Conclusions CGRP expression in the IFP of KOA patients is regulated by the COX-2/mPGES-1/PGE2 pathway.http://link.springer.com/article/10.1186/s12944-018-0864-8Calcitonin gene-related peptide/SEOsteoarthritis, kneeAdipose tissue/PPProstaglandin E2
spellingShingle Jun Aikawa
Kentaro Uchida
Shotaro Takano
Gen Inoue
Dai Iwase
Masayuki Miyagi
Manabu Mukai
Shintaro Shoji
Hiroyuki Sekiguchi
Masashi Takaso
Regulation of calcitonin gene-related peptide expression through the COX-2/mPGES-1/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritis
Lipids in Health and Disease
Calcitonin gene-related peptide/SE
Osteoarthritis, knee
Adipose tissue/PP
Prostaglandin E2
title Regulation of calcitonin gene-related peptide expression through the COX-2/mPGES-1/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritis
title_full Regulation of calcitonin gene-related peptide expression through the COX-2/mPGES-1/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritis
title_fullStr Regulation of calcitonin gene-related peptide expression through the COX-2/mPGES-1/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritis
title_full_unstemmed Regulation of calcitonin gene-related peptide expression through the COX-2/mPGES-1/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritis
title_short Regulation of calcitonin gene-related peptide expression through the COX-2/mPGES-1/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritis
title_sort regulation of calcitonin gene related peptide expression through the cox 2 mpges 1 pge2 pathway in the infrapatellar fat pad in knee osteoarthritis
topic Calcitonin gene-related peptide/SE
Osteoarthritis, knee
Adipose tissue/PP
Prostaglandin E2
url http://link.springer.com/article/10.1186/s12944-018-0864-8
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