van Meurs J B, van Lent P L, Singer I I, Bayne E K, van de Loo F A, van den Berg W B
University Hospital Nijmegen, The Netherlands.
Arthritis Rheum. 1998 Apr;41(4):647-56. doi: 10.1002/1529-0131(199804)41:4<647::AID-ART11>3.0.CO;2-T.
To investigate the relationship between occurrence of the matrix metalloproteinase-generated neoepitope VDIPEN and proteoglycan (PG) loss in arthritis, and to examine the role of interleukin-1 (IL-1) in VDIPEN expression.
VDIPEN expression was investigated in murine antigen-induced arthritis by immunolocalization studies on joint sections. The involvement of IL-1 in VDIPEN expression was studied by blocking of IL-1 using IL-1 receptor antagonist (IL-1Ra).
Profound PG loss was evident early in arthritis, without significant VDIPEN expression. Full expression of the neoepitope appeared after a few days, when PG depletion was severe, and disappeared at late stages when cartilage showed recovery from PG depletion. At sites where chondrocyte death occurred and cartilage did not recover from the initial cartilage depletion, VDIPEN expression remained present. Prophylactic IL-1Ra treatment of arthritic mice resulted in almost complete prevention of VDIPEN expression. However, IL-1Ra had only a minor effect on PG depletion, emphasizing that there is no correlation between VDIPEN and early PG depletion.
This study indicates that IL-1 is involved in VDIPEN expression. Although VDIPEN-inducing metalloproteinases do not seem to be involved in early PG depletion during antigen-induced arthritis, metalloproteinase neoepitopes are present when PG depletion is severe.
研究基质金属蛋白酶产生的新表位VDIPEN的出现与关节炎中蛋白聚糖（PG）丢失之间的关系，并探讨白细胞介素-1（IL-1）在VDIPEN表达中的作用。
通过对关节切片进行免疫定位研究，在小鼠抗原诱导的关节炎中研究VDIPEN的表达。使用IL-1受体拮抗剂（IL-1Ra）阻断IL-1，研究IL-1在VDIPEN表达中的作用。
在关节炎早期，PG明显大量丢失，但无明显的VDIPEN表达。新表位在几天后完全表达，此时PG消耗严重，而在软骨从PG消耗中恢复的后期阶段消失。在软骨细胞死亡且软骨未从初始软骨消耗中恢复的部位，VDIPEN表达仍然存在。对关节炎小鼠进行预防性IL-1Ra治疗几乎完全预防了VDIPEN的表达。然而，IL-1Ra对PG消耗的影响很小，这强调了VDIPEN与早期PG消耗之间没有相关性。
本研究表明IL-1参与VDIPEN的表达。虽然诱导VDIPEN的金属蛋白酶似乎不参与抗原诱导的关节炎早期的PG消耗，但在PG消耗严重时存在金属蛋白酶新表位。
