Phosphocitrate blocks calcification-induced articular joint degeneration in a guinea pig model
Phosphocitrate blocks calcification-induced articular joint degeneration in a guinea pig model
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DOI：
10.1002/art.22017
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发表时间：
2006-08-01
影响因子：
--
通讯作者：
Wierzbicki, Andrzej
中科院分区：
文献类型：
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作者：
Cheung, Herman S.;Sallis, John D.;Wierzbicki, Andrzej
Objective.骨关节炎（OA）关节中经常发生钙沉积。然而，钙化在软骨退变中的因果作用的证据是推论性的。本研究旨在研究钙化在OA疾病进展中的作用，并评估磷酸柠檬酸盐（PC）作为潜在治疗药物的制剂。我们已经确定了一个豚鼠OA模型，其中钙化似乎与衰老和疾病进展相关。我们合成了一种新的PC制剂[CaNa（PC）（2）（H2O）]（n）（CaNaPC），它是一种有效的抗矿化剂和晶体诱导生物效应的特异性抑制剂。在用CaNaPC每周治疗实验性OA的豚鼠3个月后，我们检查了椎间盘钙化和软骨退化。作为对照，我们检查了类似的CaNaPC治疗是否在半结肠切除术模型中有任何治疗效果，其中没有已知的晶体参与。在该动物模型中，半月板钙化与软骨退变相关。PC治疗导致钙沉积显著减少并阻止OA疾病进展。相似的处理在半结肠切除模型中没有效果。CaNaPC减少了皮肤钙化模型和OA模型中的矿化，其中关节内矿化是突出特征。在OA豚鼠模型中，钙化的抑制伴随着软骨退化的减少。CaNaPC在半半月板切除模型中没有治疗作用。我们得出结论，病理性钙化可能会启动或放大导致软骨退变的过程，CaNaPC可能会中断这样的途径。
Objective. Calcium deposition occurs frequently in osteoarthritic (OA) joints. However, evidence for a causal role of calcification in cartilage degeneration is inferential. The present study was undertaken to examine the role of calcification in OA disease progression and to evaluate a formulation of phosphocitrate (PC) as a potential therapeutic agent.Methods. We have identified a guinea pig OA model in which meniscal calcification appears to correlate with aging and disease progression. We synthesized a new formulation of PC, [CaNa(PC)(2)(H2O)](n) (CaNaPC), which is a potent antimineralization agent and a specific inhibitor of crystal-induced biologic effects. After weekly treatment of guinea pigs with experimental OA with CaNaPC for 3 months, we examined calcification in menisci and cartilage degeneration. As a control, we examined whether similar CaNaPC treatment had any therapeutic effect in a hemi-meniscectomy model in which there is no known crystal involvement.Results. Meniscal calcification correlated with cartilage degeneration in this animal model. PC treatment led to significant reduction of calcium deposits and arrested OA disease progression. Similar treatment had no effect in the hemi-meniscectomy model.Conclusion. CaNaPC diminishes mineralization in a cutaneous calcergy model and a model of OA in which intraarticular mineralization is a prominent feature. In the OA guinea pig model, inhibition of calcification is accompanied by diminished cartilage degeneration.. CaNaPC has no therapeutic effect in the hemimeniscectomy model. We conclude that pathologic calcification may initiate or amplify processes leading to cartilage degeneration and that CaNaPC may interrupt such a pathway.