Kanbe K, Takemura T, Takeuchi K, Chen Q, Takagishi K, Inoue K
Department of Orthopaedic Surgery, Tokyo Women's Medical University, Daini Hospital, Japan.
J Bone Joint Surg Br. 2004 Mar;86(2):296-300. doi: 10.1302/0301-620x.86b2.14474.
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.
我们比较了滑膜切除术或全膝关节置换术(TKR)前后血清中基质细胞衍生因子-1(SDF-1)、基质金属蛋白酶-1(MMP-1)、MMP-9和MMP-13的浓度。我们通过免疫组织化学证实了滑膜和关节软骨中存在SDF-1及其受体CXCR4。我们通过使用突变型CXCR4来阻断基质金属蛋白酶的释放从而建立软骨细胞。与手术前相比,滑膜切除术后骨关节炎(OA)和类风湿关节炎(RA)患者血清中SDF-1水平分别下降了5.1倍和6.7倍。滑膜切除术后OA和RA患者的MMP-9和MMP-13水平降低。我们在滑膜和骨髓中检测到了SDF-1,但在软骨中未检测到。在关节软骨中检测到了CXCR4。SDF-1以剂量依赖的方式增加了软骨细胞中MMP-9和MMP-13的释放。突变型CXCR4通过逆转录病毒载体阻断了软骨细胞中MMP-9和MMP-13的释放。滑膜切除术对OA或RA患者有效,因为手术去除了可调节关节软骨细胞释放MMP-9和MMP-13以破坏软骨的SDF-1。