Naproxen, meloxicam and methylprednisolone inhibit urokinase plasminogen activator and inhibitor and gelatinases expression during the early stage of osteoarthritis.

BACKGROUND: To test the hypothesis that naproxen, meloxicam and methylprednisolone down-regulate the plasminogen activator (PA)/plasmin system and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] expression during early development of osteoarthritis (OA). METHODS: Samples of human OA articular cartilage, meniscus and synovium were obtained at knee arthroscopy and cultured ex vivo with or without naproxen, meloxicam or methylprednisolone. MMP-2 and MMP-9 levels were evaluated by gelatin zymography and urokinase-type PA (u-PA) and PA inhibitor-1 (PAI-1) levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Gelatin zymography revealed that naproxen, meloxicam and methylprednisolone could suppress MMP-2 secretion in all tissue cultures and MMP-9 production in meniscal and synovial cultures. ELISA showed that naproxen and meloxicam reduced u-PA secretion in chondral and synovial cultures at 48 h except in naproxen-treated chondral cultures. On PAI-1 secretion, naproxen and meloxicam had the suppressive effects in all cultures at 48 h but not in naproxen-treated meniscal cultures. Methylprednisolone also decreased u-PA secretion in chondral and synovial cultures and PAI-1 production in synovial cultures at 48 h. CONCLUSION: Naproxen, meloxicam and methylprednisolone can down-regulate the PA/plasmin system and gelatinases expression in the early osteoarthritic knee of humans, thereby possibly have a potential structure-modifying activity in a limited use.

Arthroscopic treatment for gouty tophi mimicking an intra-articular synovial tumor of the knee.

Tophi deposition is a well-recognized complication of chronic gout, but usually lacks obvious symptoms. Magnetic resonance imaging (MRI) findings may allow a relatively specific diagnosis to be rendered. In this study, we report an unusual case of gouty tophi presenting as an intra-articular synovial tumor of the knee, blocking the range of motion. We also describe its MRI appearance, which was compatible with the clinical suspicion. After arthroscopic excision of the "tumor," the patient was symptom free.

Upregulation of urokinase-type plasminogen activator and inhibitor and gelatinase expression via 3 mitogen-activated protein kinases and PI3K pathways during the early development of osteoarthritis.

OBJECTIVE: To examine whether upregulation of urokinase-type plasminogen activator (u-PA), PA inhibitor-1 (PAI-1), and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] in early knee osteoarthritis (OA) of humans occurs through 3 major mitogen-activated protein kinases (MAPK): extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase signaling pathways, and the phosphatidylinositol 3-kinase (PI3K) signaling pathway. METHODS: Enzyme linked immunosorbent assay and gelatin zymography were used to investigate the effects of ERK 1/2 inhibitor U0126, JNK and p38 inhibitor SB203580, and PI3K inhibitor LY294002 on the secretion of u-PA, PAI-1, MMP-2, and MMP-9 in early osteoarthritic tissue cultures, with or without interleukin 1alpha (IL-1alpha) and lipopolysaccharide (LPS) induction. RESULTS: Our findings were: (1) latent and active forms of MMP-9 secretion in synovial and some meniscal cultures were inhibited significantly by U0126, SB203580, and LY294002; (2) latent and active forms of MMP-2 secretion were also inhibited significantly by U0126 and LY294002, but not by SB203580, except for active MMP-2 in synovial cultures; (3) a similar observation was seen in IL-1alpha- and LPS-treated cultures; and (4) U0126, SB203580, and LY294002 significantly decreased u-PA and PAI-1 levels in all cultures in the presence or absence of IL-1alpha and LPS. CONCLUSION: MAPK ERK, JNK, and p38 signaling pathways and the PI3K signaling pathway are involved in upregulation of u-PA, PAI-1, and gelatinase expression during early development of knee OA. Thus, blocking PA/plasmin and gelatinase expression by novel physiologic and pharmacological inhibitors could be an important therapeutic or preventive approach for early OA.