TY - JOUR
T1 - Fluid shear stress-induced osteoarthritis
T2 - Roles of cyclooxygenase-2 and its metabolic products in inducing the expression of proinflammatory cytokines and matrix metalloproteinases
AU - Wang, Pu
AU - Guan, Pei Pei
AU - Guo, Chuang
AU - Zhu, Fei
AU - Konstantopoulos, Konstantinos
AU - Wang, Zhan You
PY - 2013/12
Y1 - 2013/12
N2 - The mechanical overloading of cartilage is involved in the pathophysiology of osteoarthritis (OA) by both biochemical and mechanical pathways. The application of fluid shear stress to chondrocytes recapitulates the earmarks of OA, as evidenced by the release of proinflammatory cytokines (PICs), matrix metalloproteinases (MMPs), and apoptotic factors. Dysregulations or mutations in these genes might directly cause OA in addition to determining the stage at which OA becomes apparent, the joint sites involved, and the severity of the disease and how rapidly it progresses. However, the underlying mechanisms remain unknown. In this review, we propose that the dysregulation of cyclooxygenase-2 (COX-2) is associated with fluid shear stress-induced OA via its metabolic products at different stages of the disease. Indeed, high fluid shear stress rapidly induces the production of PICs and MMPs via COX-2-derived prostaglandin (PG)E2 at the early stage of OA. In contrast, prolonged shear exposure (>12 h) aggravates the condition by concurrently up-regulating the expression of proapoptotic genes and down-regulating the expression of antiapoptotic genes in a 15-deoxy- (12,14)-prostaglandin J2 (15d-PGJ2)-dependent manner at the late stage of disease. These observations may help to resolve long-standing questions in OA progression and provide insight for development of strategies to treat and combat OA.-Wang, P., Guan, P.-P., Guo, C., Zhu, F., Konstantopoulos, K., Wang, Z.-W. Fluid shear stressinduced osteoarthritis: roles of cyclooxygenase-2 and its metabolic products in inducing the expression of proinflammatory cytokines and matrix metalloproteinases.
AB - The mechanical overloading of cartilage is involved in the pathophysiology of osteoarthritis (OA) by both biochemical and mechanical pathways. The application of fluid shear stress to chondrocytes recapitulates the earmarks of OA, as evidenced by the release of proinflammatory cytokines (PICs), matrix metalloproteinases (MMPs), and apoptotic factors. Dysregulations or mutations in these genes might directly cause OA in addition to determining the stage at which OA becomes apparent, the joint sites involved, and the severity of the disease and how rapidly it progresses. However, the underlying mechanisms remain unknown. In this review, we propose that the dysregulation of cyclooxygenase-2 (COX-2) is associated with fluid shear stress-induced OA via its metabolic products at different stages of the disease. Indeed, high fluid shear stress rapidly induces the production of PICs and MMPs via COX-2-derived prostaglandin (PG)E2 at the early stage of OA. In contrast, prolonged shear exposure (>12 h) aggravates the condition by concurrently up-regulating the expression of proapoptotic genes and down-regulating the expression of antiapoptotic genes in a 15-deoxy- (12,14)-prostaglandin J2 (15d-PGJ2)-dependent manner at the late stage of disease. These observations may help to resolve long-standing questions in OA progression and provide insight for development of strategies to treat and combat OA.-Wang, P., Guan, P.-P., Guo, C., Zhu, F., Konstantopoulos, K., Wang, Z.-W. Fluid shear stressinduced osteoarthritis: roles of cyclooxygenase-2 and its metabolic products in inducing the expression of proinflammatory cytokines and matrix metalloproteinases.
KW - 15d-PGJ2
KW - Apoptosis
KW - Chondrocytes
KW - Inflammation
KW - PGE2
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U2 - 10.1096/fj.13-234542
DO - 10.1096/fj.13-234542
M3 - Review article
C2 - 23964078
AN - SCOPUS:84890482110
SN - 0892-6638
VL - 27
SP - 4664
EP - 4677
JO - FASEB Journal
JF - FASEB Journal
IS - 12
ER -