Intermittent hydrostatic pressure inhibits shear stress-induced nitric oxide release in human osteoarthritic chondrocytes in vitro.
OBJECTIVE
To test the effects of intermittent hydrostatic pressure (IHP) on nitric oxide (NO) release induced by shear stress and matrix macromolecule gene expression in human osteoarthritic chondrocytes in vitro.


METHODS
Chondrocytes isolated from cartilage samples from 9 patients with osteoarthritis were cultured and exposed to either shear stress or an NO donor. Nitrite concentration was measured using the Griess reaction. Matrix macromolecule mRNA signal levels were determined using reverse-transcriptase polymerase chain reaction and quantified by imaging analysis software.


RESULTS
Exposure to shear stress upregulated NO release in a dose and time-dependent manner. Application of IHP inhibited shear stress induced NO release but did not alter NO release from chondrocytes not exposed to shear stress. Shear stress induced NO or addition of an NO donor (sodium nitroprusside) was associated with decreased mRNA signal levels for the cartilage matrix proteins, aggrecan, and type II collagen. Intermittent hydrostatic pressure blocked the inhibitory effects of sodium nitroprusside but did not alter the inhibitory effects of shear stress on cartilage macromolecule gene expression.


CONCLUSIONS
Our data show that shear stress and IHP differentially alter chondrocyte metabolism and suggest that a balance of effects between different loading forces preserve cartilage extracellular matrix in vivo.
Lee
Mel S
MS
Orthopaedic Research Laboratory and the Division of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, USA.
Trindade
Michael C D
MC
Ikenoue
Takashi
T
Schurman
David J
DJ
Goodman
Stuart B
SB
Smith
R Lane
RL
D053674:Aggrecans; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D006801:Humans; D006874:Hydrostatic Pressure; D066298:In Vitro Techniques; D037181:Lectins, C-Type; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010003:Osteoarthritis / Q000378:metabolism* / Q000503:physiopathology; D011509:Proteoglycans / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013314:Stress, Mechanical
D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D020030:Nitric Oxide Donors; D011509:Proteoglycans; D012333:RNA, Messenger; D009599:Nitroprusside; D009569:Nitric Oxide; D003094:Collagen