Cyclic phosphatidic acid relieves osteoarthritis symptoms.
Cyclic phosphatidic acid relieves osteoarthritis symptoms.
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DOI：
10.1186/1744-8069-10-52
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发表时间：
2014-08-14
期刊：
影响因子：
3.3
通讯作者：
Murakami-Murofushi K
中科院分区：
文献类型：
--
作者：
Gotoh M;Nagano A;Tsukahara R;Murofushi H;Morohoshi T;Otsuka K;Murakami-Murofushi K
环状磷脂酸（cPA）是一种天然存在的磷脂介质，在其甘油骨架的sn-2和sn-3位置具有独特的环状磷酸环。天然cPA及其化学稳定的cPA衍生物2-carb-cPA（2ccPA）可抑制慢性和急性炎症，2ccPA可减轻神经性疼痛。骨关节炎（OA）是一种退行性疾病，常伴有炎症和关节疼痛等症状。由于2ccPA具有明显的镇痛作用，我们推测2ccPA可能减轻OA引起的疼痛。我们的目的是表征2ccPA对兔膝关节全关节切除术诱导的OA发病机制的影响。关节内注射2ccPA（每周两次，持续42天）可显著减轻疼痛和关节肿胀。组织学显示2ccPA抑制OA中的软骨退变。我们还研究了2ccPA对体外人OA滑膜细胞和软骨肉瘤SW 1353细胞的炎症和分解代谢反应的影响。2ccPA刺激透明质酸的合成并抑制金属蛋白酶MMP-1、MMP-3和MMP-13的产生。然而，它对白细胞介素（IL）-6（一种炎症细胞因子）的产生没有影响。2ccPA对滑膜细胞中MMP-1和MMP-3产生以及对SW 1353细胞中MMP-13产生的抑制作用不是由溶血磷脂酸受体LPA 1受体（LPA 1 R）介导的。我们的研究结果表明，2ccPA通过诱导透明质酸产生和抑制滑膜细胞和软骨细胞中MMP-1、MMP-3和MMP-13的产生，显著降低了对OA的疼痛反应。
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.
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影响因子：
7
作者：
Kraus, V. B.;Burnett, B.;Todman, M.
通讯作者：
Todman, M.
影响因子：
--
作者：
Julovi, SM;Yasuda, T;Nakamura, T
通讯作者：
Nakamura, T
影响因子：
--
作者：
BALAZS, EA;WATSON, D;ROSEMAN, S
通讯作者：
ROSEMAN, S
环磷脂酸及其衍生物对急慢性疼痛动物模型的镇痛作用。
影响因子：
3.3
作者：
Kakiuchi Y;Nagai J;Gotoh M;Hotta H;Murofushi H;Ogawa T;Ueda H;Murakami-Murofushi K
通讯作者：
Murakami-Murofushi K
影响因子：
1.8
作者：
KOBAYASHI, S;TOKUNOH, R;MURAKAMIMUROFUSHI, K
通讯作者：
MURAKAMIMUROFUSHI, K