Joint infection

Ikenoue

Trindade

et al. 2003

The role of continuous passive motion (CPM) in the management of septic arthritis and inflammatory arthritis remains of interest. CPM produces cyclic variations in intraarticular pressure that facilitates transport of fluid, nutrients, and solutes within and/ or across the joint and stimulates chondrocyte metabolism. However, the precise mechanisms mediating the responses of chondrocytes to joint motion remain unclear. This study tested the hypothesis that dynamic mechanical loading counteracts effects of bacterial lipopolysaccharide (LPS), an inflammatory mediator, on chondrocyte metabolism. Intermittent hydrostatic pressure (IHP) (10 MPa for 4 h) was applied to human chondrocytes pretreated with LPS (1 pg/ml for 18 11). LPS activation of chondrocytes decreased mRNA signal levels of type I1 collagen by 67% and aggrecan by 56% and increased nitric oxide by 3.1-fold, monocyte chemotactic protein-1 mRNA signal levels by 6.S-fold, and matrix metalloproteinase-2 mRNA signal levels by 1 .Hold. Application of IHP to LPS-activated chondrocytes decreased nitric oxide synthase mRNA signal levels and nitric oxide levels in the culture medium. Exposure of LPS-activated chondrocytes to IHP upregulated type I1 collagen and aggrecan mRNA signal levels by 1.7-fold, relative to chondrocytes activated by LPS and maintained without loading. In addition, application of IHP decreased the upregulation in signal levels of monocyte chemotactic factor-1 and matrix metalloproteinase-2 following LPS activation by 45% and 1 S'%, respectively. These data show that mechanical loading counteract effects of inflammatory agents, such as bacterial LPS, and suggest that postinfection sequelae are influenced by the presence or absence of joint loading. lntroduction Septic arthritis remains a potentially destructive disorder of synovial joints and often exhibits residual joint destruction [22,33]. In spite of prompt diagnosis and treatment, up to 50% of glycosaminoglycan and 37% of collagen may be lost from the cartilage matrix in infected joints [22,26,29,33]. Adjunctive treatments to ameliorate postinfectious sequelae such as nonsteroidal anti-inflammatory drugs or inhibitors of reactive oxygen species only partially lessen release of factors involved in joint tissue breakdown [15,28,29].

Section: Lntroductionmentioning

confidence: 99%

Section: Lntroductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Protective effects of intermittent hydrostatic pressure on osteoarthritic chondrocytes activated by bacterial endotoxin in vitro

Ikenoue

Trindade

et al. 2003

“…Collective data confirmed that up to 50% of glycosaminoglycans and 37% of collagen could be lost in spite of joint irrigation and early administration of antibiotics [20,21,24,25]. Adjunctive treatment with nonsteroidal anti-inflammatory drugs or inhibitors of reactive oxygen species have been used in animal models but could only partially lessen the post-infectious complications [20,23,24].…”

Section: Discussionmentioning

confidence: 91%

“…In joints with pyogenic infection, prolonged destruction of cartilage may occur in spite of prompt and effective antibiotic therapy [20,21,25]. Although secreted bacterial toxins and the host inflammatory response account for early processes of cartilage destruction [3,7,8,25,30,31], the precise mechanisms causing hypocellularity and early degenerative change after septic arthritis remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Signal transduction pathways and apoptosis in bacteria infected chondrocytes

Yen

Ueng

et al. 2001

The mechanism underlying chronic destructive arthropathy after pyogenic arthritis is not clear. This study evaluated the role of apoptosis in Staphylococcus aureus infected human articular chondrocytes and investigated the signal transduction pathways activated by bacterial infection. Chondrocytes cultured in monolayer were challenged with bacteria for 6 h and were analyzed after incubation for 2, 18, and 24 h. Chondrocytes showed morphologic and biochemical evidences of apoptosis after infection and the following incubation period. Although treatment with extensive washing and vancomycin could ameliorate the amount of apoptosis from 31% to 15% at 2 h, from 48% to 23% at 18 h, and from 58% to 33% at 24 h, the infected samples with treatment still had higher amount of apoptosis than the un-infected controls (ANOVA P < 0.001). Accompanying with the increasing amount of apoptosis, the caspase activity was upregulated in bacteria infected samples and remained high in samples with treatment (ANOVA P < 0.05).Signal transduction pathways activated by bacterial infection were assessed by co-transfection technique. After infection, the c-Jun N-terminal kinase, extracellular signal-regulated kinase, and cyclic AMP-dependent protein kinase activities were elevated by 7.6-, 7.3-, and 3.2-fold, respectively, compared to the uninfected controls. The data support the hypothesis that human chondrocytes will undergo apoptosis after infection by a single organism. Apoptosis and activated intracellular kinase activities may be related to the pathogenesis of post-infectious destructive arthropathy.

Inhibition of nitric oxide can ameliorate apoptosis and modulate matrix protein gene expression in bacteria infected chondrocytes in vitro

Chao

et al. 2005

Bacterial infection stimulates nitric oxide (NO) production in chondrocytes. However, the role of NO in chondrocyte apoptosis after infection remains unclear. The purpose of the study was to test if inhibition of NO could ameliorate apoptosis and modulate matrix protein gene expression in bacteria-infected chondrocytes. It was shown that pre-treating chondrocytes with L-NAME (1 mM) significantly decreased the release of NO (from 72 to 14 pM) and the extent of apoptosis (from 52.9% to 18.9%). Pre-treatment with L-NAME also counteracted the bacteria-induced downregulation of Type I1 collagen (from 26% to 79%) and aggrecan (from 63% to 105%) mRNA levels. Inhibition of NO after the induction of infection could not decrease the extent of apoptosis and modulate matrix protein gene expression. The results of this study support the hypothesis that NO has an important role in bacteriainduced chondrocyte apoptosis. Pre-treatment but not post-treatment could ameliorate the extent of apoptosis and reestablish the cartilage matrix protein gene expression. This study suggests that in addition to NO, other mechanisms may be responsible for the sustained destruction of articular cartilage in the post-infectious arthropathy.