ORIGINAL ARTICLE Ko-Hsiu Lu Æ Shun-Fa Yang Æ Shu-Chen Chu Pei-Ni Chen Æ Ming-Chih Chou Æ Tang-Yan Hsiao Yih-Shou Hsieh The significance of altered gelatinase expression in the synovium of patient with arthritic effusions Received: 6 January 2003 / Accepted: 9 April 2003 / Published online: 19 November 2003 Ó Clinical Rheumatology 2003 Abstract In this study we quantified the levels of matrix metalloproteinase-2 and 9 (MMP-2 and 9) in effusions and serial synovial cultures of patients with arthritis of the knee in order to investigate the correlations between MMP and cell counts in effusions as well as the possible roles of the synovium. In 49 patients with arthritis of the knee (series I) we examined the cell counts and the amounts of MMP-2 and 9 in 51 effusions. In 20 knee samples of series I of patients who received arthroscopy (series II), we examined the amounts of MMP-2 and 9 in effusions and serial synovial organ cultures. We also compared the gene expressions of MMP-2 and 9 and MT1-MMP in serial synovial cultures using RT-PCR. In series I, significantly more proMMP-9 appeared in effusions from the inflammatory group than in the non- inflammatory and hemorrhagic group (p <0.001). The levels of proMMP-9 correlated with the neutrophil counts in the effusions (p <0.001). In series II synovial cultures, the activities of latent and activated forms of MMP-2 and 9 in lesional areas were all higher than that in paralesional ones (p <0.05). In RT-PCR analysis, MMP-2, -9 and membrane type 1 MMP mRNA levels of lesional areas also showed increased expression. Our data suggest that the analysis of MMP-9 indicates the inflammatory condition of the joints and that additional synovectomy may be beneficial for patients with in- flammatory synovitis, compared with non-inflammatory and hemorrhagic arthritis. Keywords Arthritis Æ MMP-2 Æ MMP-9 Æ Neutrophils Æ Synovectomy Abbreviations ECM Extracellular matrix Æ GA Gouty arthritis Æ IDV Integrated density value Æ MMP Matrix metalloproteinases Æ OA Osteoarthritis Æ PVNS Pig- mented villonodular synovitis Æ RA Rheumatoid arthritis Æ SF Synovial fluid Æ TIMP Tissue inhibitors of metalloproteinases Æ TKA Total knee arthroplasty Introduction Matrix metalloproteinases (MMP) are a family of pro- teinases that act together to degrade all extracellular matrix (ECM) components. Their activity is controlled by specific inhibitors, known as tissue inhibitors of me- talloproteinases (TIMP), and both MMP and TIMP have been shown to have a role in developmental processes, normal cartilage turnover and wound repair [1]. The re- lease of pathologic tissue breakdown products may cause synovitis in the joint, resulting in swelling and pain. Therefore, the balance between the amounts of MMP and TIMP in synovial fluid (SF) and local tissue may be a determinant of whether MMP attack the cartilage ECM. In arthritic joints, spatially and temporally controlled expressions of MMP and their inhibitors have been confirmed and play a role in the proteolytic degradation of damaged ECM components and in tissue repair [2]. Type IV collagenases (gelatinases) are members of the family of MMP and are thought to play an important role in the degradation of extracellular components. The gelatinase subclass can be divided into gelatinase-A (MMP-2 or 72 kDa type IV collagenase) and gelatinase- B (MMP-9 or 92 kDa type IV collagenase). These enzymes are capable of degrading types IV and V col- lagen, elastin and gelatin [3, 4, 5]. The MMP are secreted as latent precursor enzymes and can be activated by Clin Rheumatol (2004) 23: 21–26 DOI 10.1007/s10067-003-0774-6 K.-H. Lu Æ T.-Y. Hsiao Department of Orthopaedic Surgery, Chung Shan Medical University Hospital, 402 Taichung, Taiwan S.-F. Yang Æ P.-N. Chen Æ M.-C. Chou Æ Y.-S. Hsieh (&) Chung Shan Medical University, No. 110, Sec.1, Chien Kuo N. Rd, 402 Taichung, Taiwan E-mail: csmcysh@csmu.edu.tw Tel.: +886-4-24730022 Fax: +886-4-24723229 S.-C. Chu Department of Food Science, Chungtai Institute of Health Sciences and Technology, 406 Taichung, Taiwan