Cargando…

Cyclic phosphatidic acid relieves osteoarthritis symptoms

BACKGROUND: Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator with a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. Natural cPA and its chemically stabilized cPA derivative, 2-carba-cPA (2ccPA), inhibit chronic and acute inflammation...

Descripción completa

Detalles Bibliográficos
Autores principales: Gotoh, Mari, Nagano, Aya, Tsukahara, Ryoko, Murofushi, Hiromu, Morohoshi, Toshiro, Otsuka, Kazuyuki, Murakami-Murofushi, Kimiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141741/
https://www.ncbi.nlm.nih.gov/pubmed/25123228
http://dx.doi.org/10.1186/1744-8069-10-52
_version_ 1782331682499592192
author Gotoh, Mari
Nagano, Aya
Tsukahara, Ryoko
Murofushi, Hiromu
Morohoshi, Toshiro
Otsuka, Kazuyuki
Murakami-Murofushi, Kimiko
author_facet Gotoh, Mari
Nagano, Aya
Tsukahara, Ryoko
Murofushi, Hiromu
Morohoshi, Toshiro
Otsuka, Kazuyuki
Murakami-Murofushi, Kimiko
author_sort Gotoh, Mari
collection PubMed
description BACKGROUND: Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator with a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. Natural cPA and its chemically stabilized cPA derivative, 2-carba-cPA (2ccPA), inhibit chronic and acute inflammation, and 2ccPA attenuates neuropathic pain. Osteoarthritis (OA) is a degenerative disease frequently associated with symptoms such as inflammation and joint pain. Because 2ccPA has obvious antinociceptive activity, we hypothesized that 2ccPA might relieve the pain caused by OA. We aimed to characterize the effects of 2ccPA on the pathogenesis of OA induced by total meniscectomy in the rabbit knee joint. RESULTS: Intra-articular injection of 2ccPA (twice a week for 42 days) significantly reduced pain and articular swelling. Histopathology showed that 2ccPA suppressed cartilage degeneration in OA. We also examined the effects of 2ccPA on the inflammatory and catabolic responses of human OA synoviocytes and chondrosarcoma SW1353 cells in vitro. 2ccPA stimulated synthesis of hyaluronic acid and suppressed production of the metalloproteinases MMP-1, -3, and -13. However, it had no effect on the production of interleukin (IL)-6, an inflammatory cytokine. The suppressive effect of 2ccPA on MMP-1 and -3 production in synoviocytes and on MMP-13 production in SW1353 cells was not mediated by the lysophosphatidic acid receptor, LPA1 receptor (LPA1R). CONCLUSIONS: Our results suggest that 2ccPA significantly reduces the pain response to OA by inducing hyaluronic acid production and suppressing MMP-1, -3, and -13 production in synoviocytes and chondrocytes.
format Online
Article
Text
id pubmed-4141741
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-41417412014-08-28 Cyclic phosphatidic acid relieves osteoarthritis symptoms Gotoh, Mari Nagano, Aya Tsukahara, Ryoko Murofushi, Hiromu Morohoshi, Toshiro Otsuka, Kazuyuki Murakami-Murofushi, Kimiko Mol Pain Research BACKGROUND: Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator with a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. Natural cPA and its chemically stabilized cPA derivative, 2-carba-cPA (2ccPA), inhibit chronic and acute inflammation, and 2ccPA attenuates neuropathic pain. Osteoarthritis (OA) is a degenerative disease frequently associated with symptoms such as inflammation and joint pain. Because 2ccPA has obvious antinociceptive activity, we hypothesized that 2ccPA might relieve the pain caused by OA. We aimed to characterize the effects of 2ccPA on the pathogenesis of OA induced by total meniscectomy in the rabbit knee joint. RESULTS: Intra-articular injection of 2ccPA (twice a week for 42 days) significantly reduced pain and articular swelling. Histopathology showed that 2ccPA suppressed cartilage degeneration in OA. We also examined the effects of 2ccPA on the inflammatory and catabolic responses of human OA synoviocytes and chondrosarcoma SW1353 cells in vitro. 2ccPA stimulated synthesis of hyaluronic acid and suppressed production of the metalloproteinases MMP-1, -3, and -13. However, it had no effect on the production of interleukin (IL)-6, an inflammatory cytokine. The suppressive effect of 2ccPA on MMP-1 and -3 production in synoviocytes and on MMP-13 production in SW1353 cells was not mediated by the lysophosphatidic acid receptor, LPA1 receptor (LPA1R). CONCLUSIONS: Our results suggest that 2ccPA significantly reduces the pain response to OA by inducing hyaluronic acid production and suppressing MMP-1, -3, and -13 production in synoviocytes and chondrocytes. BioMed Central 2014-08-14 /pmc/articles/PMC4141741/ /pubmed/25123228 http://dx.doi.org/10.1186/1744-8069-10-52 Text en Copyright © 2014 Gotoh et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Gotoh, Mari
Nagano, Aya
Tsukahara, Ryoko
Murofushi, Hiromu
Morohoshi, Toshiro
Otsuka, Kazuyuki
Murakami-Murofushi, Kimiko
Cyclic phosphatidic acid relieves osteoarthritis symptoms
title Cyclic phosphatidic acid relieves osteoarthritis symptoms
title_full Cyclic phosphatidic acid relieves osteoarthritis symptoms
title_fullStr Cyclic phosphatidic acid relieves osteoarthritis symptoms
title_full_unstemmed Cyclic phosphatidic acid relieves osteoarthritis symptoms
title_short Cyclic phosphatidic acid relieves osteoarthritis symptoms
title_sort cyclic phosphatidic acid relieves osteoarthritis symptoms
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141741/
https://www.ncbi.nlm.nih.gov/pubmed/25123228
http://dx.doi.org/10.1186/1744-8069-10-52
work_keys_str_mv AT gotohmari cyclicphosphatidicacidrelievesosteoarthritissymptoms
AT naganoaya cyclicphosphatidicacidrelievesosteoarthritissymptoms
AT tsukahararyoko cyclicphosphatidicacidrelievesosteoarthritissymptoms
AT murofushihiromu cyclicphosphatidicacidrelievesosteoarthritissymptoms
AT morohoshitoshiro cyclicphosphatidicacidrelievesosteoarthritissymptoms
AT otsukakazuyuki cyclicphosphatidicacidrelievesosteoarthritissymptoms
AT murakamimurofushikimiko cyclicphosphatidicacidrelievesosteoarthritissymptoms