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Cyclic phosphatidic acid relieves osteoarthritis symptoms

Mari Gotoh1, Aya Nagano1, Ryoko Tsukahara123, Hiromu Murofushi2, Toshiro Morohoshi3, Kazuyuki Otsuka4 and Kimiko Murakami-Murofushi1*

Author Affiliations

1 Endowed Research Division of Human Welfare Sciences, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo 112-8610, Japan

2 Science and Education Center, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo 112-8610, Japan

3 SANSHO Co. Ltd, 1-2-10 Nihonbashi, Chuo-ku, Tokyo 103-0027, Japan

4 Osaka Biomedical Professional School, 1-14-30 Shimanouchi, Chuo-ku, Osaka 570-0011, Japan

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Molecular Pain 2014, 10:52  doi:10.1186/1744-8069-10-52

Published: 14 August 2014



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.


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).


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.

Cyclic phosphatidic acid; 2-carba-cyclic phosphatidic acid; Osteoarthritis; Total meniscectomy; Synoviocytes; Chondrocytes; Chonrosarcoma SW1353 cells; Hyaluronic acid; Metalloproteinase