Synovectomy reduces stromal-cell-derived factor-1 (SDF-1) which is involved in the destruction of cartilage in osteoarthritis and rheumatoid arthritis

Synovectomy reduces stromal-cell-derived factor-1 (SDF-1) which is involved in the destruction of cartilage in osteoarthritis and rheumatoid arthritis
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DOI:
10.1302/0301-620x.86b2.14474
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发表时间:
2004-03-01
影响因子:
--
通讯作者:
Inoue, K
Inoue, K
中科院分区:
其他
文献类型:
--
作者:
Kanbe, K;Takemura, T;Inoue, K

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我们比较了滑膜切除术或全膝关节置换术(TKR)前后血清基质细胞衍生因子-1(SDF-1)、基质金属蛋白酶-1(MMP-1)、MMP-9和MMP-13的浓度。我们通过免疫组化证实了SDF-1及其受体CXCR 4在滑膜和关节软骨中的存在。我们用突变型CXCR 4阻断MMPs的释放建立了软骨细胞,OA和RA患者滑膜切除后血清中SDF-1的水平分别比手术前降低了5.1和6.7倍。滑膜切除术后,OA和RA患者MMP-9和MMP-13均降低。我们在滑膜和骨髓中检测到SDF-1,但在软骨中未检测到。CXCR 4在关节软骨中表达。SDF-1以剂量依赖性方式增加软骨细胞MMP-9和MMP-13的释放。突变型CXCR 4通过逆转录病毒载体阻断了软骨细胞释放MMP-9和MMP-13,滑膜切除术对OA或RA患者有效,因为手术去除了SDF-1,SDF-1可以调节关节软骨细胞释放MMP-9和MMP-13,破坏软骨。
We have compared the concentrations of stromal-cell-derived factor-1 (SDF-1), matrix metalloproteinase-1 (MMP-1), MMP-9 and MMP-13 in serum before and after synovectomy or total knee replacement (TKR). We confirmed the presence of SDF-1 and its receptor CXCR4 in the synovium and articular cartilage by immunohistochemistry. We established chondrocytes by using mutant CXCR4 to block the release of MMPs.The level of SDF-1 was decreased 5.1- and 6.7-fold in the serum of patients with OA and RA respectively, after synovectomy compared with that before surgery. MMP-9 and MMP-13 were decreased in patients with OA and RA after synovectomy. We detected SDF-1 in the synovium and the bone marrow but not in cartilage. CXCR4 was detected in articular cartilage. SDF-1 increased the release of MMP-9 and MMP-13 from chondrocytes in a dose-dependent manner. The mutant CXCR4 blocked the release of MMP-9 and MMP-13 from chondrocytes by retrovirus vector.Synovectomy is effective in patients with OA or RA because SDF-1, which can regulate the release of MMP-9 and MMP-13 from articular chondrocytes for breakdown of cartilage, is removed by the operation.