Protective effects of intermittent hydrostatic pressure on osteoarthritic chondrocytes activated by bacterial endotoxin in vitro.
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 microg/ml for 18 h). LPS activation of chondrocytes decreased mRNA signal levels of type II collagen by 67% and aggrecan by 56% and increased nitric oxide by 3.1-fold, monocyte chemotactic protein-1 mRNA signal levels by 6.5-fold, and matrix metalloproteinase-2 mRNA signal levels by 1.3-fold. 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 II 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 15%, 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.
Lee
Mel S
MS
Rehabilitation R&D Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA.
Ikenoue
Takashi
T
Trindade
Michael C D
MC
Wong
Neal
N
Goodman
Stuart B
SB
Schurman
David J
DJ
Smith
R Lane
RL
D051722:ADAM Proteins; D000071121:ADAMTS4 Protein; D053674:Aggrecans; D002358:Cartilage, Articular / Q000166:cytology; D018932:Chemokine CCL2 / Q000235:genetics; D019902:Chondrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D024043:Collagen Type II / Q000235:genetics; D015536:Down-Regulation / Q000502:physiology; D016326:Extracellular Matrix Proteins; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D006874:Hydrostatic Pressure; D018836:Inflammation Mediators / Q000494:pharmacology; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008666:Metalloendopeptidases / Q000235:genetics; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010003:Osteoarthritis / Q000276:immunology* / Q000473:pathology; D011348:Procollagen N-Endopeptidase; D011509:Proteoglycans / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
D053674:Aggrecans; D018932:Chemokine CCL2; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D018836:Inflammation Mediators; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D011509:Proteoglycans; D012333:RNA, Messenger; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D011348:Procollagen N-Endopeptidase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000071121:ADAMTS4 Protein