Department of Bioscience, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, UK.
Osteoarthritis Cartilage. 2009 Oct;17(10):1333-40. doi: 10.1016/j.joca.2009.04.022. Epub 2009 May 7.
The role of calcium phosphate and pyrophosphate crystals in osteoarthritis (OA) is unclear: are they a symptom of the damage that occurs to the joint or a key intermediate in the progression of inflammation and joint damage that occurs in OA? The proinflammatory and catabolic response of synthetic calcium phosphate and pyrophosphate crystals and crystals extracted from human osteoarthritic knee cartilage has been investigated. The crystal forms eliciting a response have been characterised allowing a comparison of the biological effects of synthetic and native calcium crystals on human osteoarthritic chondrocytes and synoviocytes to be carried out.
Calcium phosphate and pyrophosphate crystals were synthesised in vitro and their crystal forms characterised by X-ray powder diffraction (XRPD). The inorganic crystalline material present in human osteoarthritic cartilage was extracted and its structural composition elucidated by XRPD. These crystals were applied to human primary osteoarthritic chondrocytes and synoviocytes and the production of proinflammatory and catabolic mediators measured.
The crystals extracted from human osteoarthritic knee cartilage were identified as consisting of a mixture of monoclinic and triclinic calcium pyrophosphate dihydrate (m-CPPD and t-CPPD). These crystals elicited an inflammatory and catabolic response in human primary osteoarthritic chondrocytes and synoviocytes as measured by an increase in nitric oxide (NO), matrix metalloproteinase 13 (MMP-13) and prostaglandin E2 (PGE(2)) production. NO, MMP-13 and PGE(2) production was also increased when the synthetic calcium hydrogen phosphate dihydrate (DCPD) and calcium pyrophosphate hydrates were applied to the cells.
Crystals extracted from human osteoarthritic knee cartilage induce the production of proinflammatory and catabolic mediators (NO, MMP-13 and PGE(2)) in human primary chondrocytes and synoviocytes. Synthetic calcium phosphate and pyrophosphate crystals elicit a similar response in those cells. Our findings suggest that these crystals could contribute to cartilage degradation and synovitis in OA.
钙磷酸盐和焦磷酸盐晶体在骨关节炎（OA）中的作用尚不清楚：它们是关节损伤的症状，还是 OA 中炎症和关节损伤进展的关键中间产物？本文研究了合成钙磷酸盐和焦磷酸盐晶体以及从人 OA 膝关节软骨中提取的晶体的促炎和分解代谢反应。对引起反应的晶体形态进行了特征描述，从而可以比较合成和天然钙晶体对人 OA 软骨细胞和滑膜细胞的生物学效应。
体外合成钙磷酸盐和焦磷酸盐晶体，并通过 X 射线粉末衍射（XRPD）对其晶体形态进行表征。通过 XRPD 阐明人 OA 软骨中存在的无机结晶物质的结构组成。将这些晶体应用于人原发性 OA 软骨细胞和滑膜细胞，并测量促炎和分解代谢介质的产生。
从人 OA 膝关节软骨中提取的晶体被鉴定为由一水合二氯化钙焦磷酸盐的单斜晶系和三斜晶系混合物（m-CPPD 和 t-CPPD）组成。这些晶体通过增加一氧化氮（NO）、基质金属蛋白酶 13（MMP-13）和前列腺素 E2（PGE2）的产生，在人原发性 OA 软骨细胞和滑膜细胞中引起炎症和分解代谢反应。当将二水合磷酸氢钙（DCPD）和焦磷酸钙水合物施加到细胞上时，NO、MMP-13 和 PGE2 的产生也增加了。
从人 OA 膝关节软骨中提取的晶体诱导人原发性软骨细胞和滑膜细胞产生促炎和分解代谢介质（NO、MMP-13 和 PGE2）。合成的钙磷酸盐和焦磷酸盐晶体在这些细胞中引起类似的反应。我们的研究结果表明，这些晶体可能导致 OA 中的软骨降解和滑膜炎。
