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].