Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
J Biol Chem. 2012 Jun 22;287(26):22216-26. doi: 10.1074/jbc.M112.356816. Epub 2012 May 1.
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by bone erosion and cartilage destruction in the joints. Many of the conventional antiarthritic drugs are effective in suppressing inflammation, but they do not offer protection against bone damage. Furthermore, the prolonged use of these drugs is associated with severe adverse reactions. Thus, new therapeutic agents that can control both inflammation and bone damage but with minimal side effects are sought. Celastrus is a Chinese herb that has been used for centuries in folk medicine for the treatment of various inflammatory diseases. However, its utility for protection against inflammation-induced bone damage in arthritis and the mechanisms involved therein have not been examined. We tested celastrus and its bioactive component celastrol for this attribute in the adjuvant-induced arthritis model of RA. The treatment of arthritic rats with celastrus/celastrol suppressed inflammatory arthritis and reduced bone and cartilage damage in the joints as demonstrated by histology and bone histomorphometry. The protective effects against bone damage are mediated primarily via the inhibition of defined mediators of osteoclastic bone remodeling (e.g. receptor activator of nuclear factor-κB ligand (RANKL)), the deviation of RANKL/osteoprotegerin ratio in favor of antiosteoclastic activity, and the reduction in osteoclast numbers. Furthermore, both the upstream inducers (proinflammatory cytokines) and the downstream effectors (MMP-9) of the osteoclastogenic mediators were altered. Thus, celastrus and celastrol controlled inflammation-induced bone damage by modulating the osteoimmune cross-talk. These natural products deserve further consideration and evaluation as adjuncts to conventional therapy for RA.
类风湿关节炎（RA）是一种慢性炎症性疾病，其特征是关节中的骨侵蚀和软骨破坏。许多传统的抗关节炎药物在抑制炎症方面有效，但它们不能提供对骨损伤的保护。此外，这些药物的长期使用与严重的不良反应有关。因此，人们正在寻找新的治疗药物，这些药物既能控制炎症又能控制骨损伤，但副作用最小。长春花是一种中国草药，在民间医学中已使用了几个世纪，用于治疗各种炎症性疾病。然而，它在预防关节炎炎症引起的骨损伤及其相关机制方面的应用尚未得到检验。我们测试了长春花及其生物活性成分长春碱在佐剂诱导的 RA 模型中的这种特性。长春花/长春碱治疗关节炎大鼠可抑制炎症性关节炎，并通过组织学和骨组织形态计量学减少关节中的骨和软骨损伤。对骨损伤的保护作用主要是通过抑制破骨细胞骨重塑的特定介质（例如核因子-κB 配体受体激活剂（RANKL））来介导的，有利于抗破骨细胞活性的 RANKL/骨保护素比值的偏离，以及破骨细胞数量的减少。此外，破骨细胞生成介质的上游诱导剂（促炎细胞因子）和下游效应物（MMP-9）都发生了改变。因此，长春花和长春碱通过调节骨免疫交叉对话来控制炎症引起的骨损伤。这些天然产物值得进一步考虑和评估，作为 RA 常规治疗的辅助手段。
