Cyclic strain stimulates proliferative capacity, alpha2 and alpha5 integrin, gene marker expression by human articular chondrocytes propagated on flexible silicone membranes.
Chondrocytes comprise less than 10% of cartilage tissue but are responsible for sensing and responding to mechanical stimuli imposed on the joint. However, the effect of mechanical signals at the cellular level is not yet fully defined. The purpose of this study was to test the hypothesis that mechanical stimulation in the form of cyclic strain modulates proliferative capacity and integrin expression of chondrocytes from osteoarthritic knee joints. Chondrocytes isolated from articular cartilage during total knee arthroplasty were propagated on flexible silicone membranes. The cells were subjected to cyclic strain for 24 h using a computer-controlled vacuum device, with replicate samples maintained under static conditions. Our results demonstrated increase in proliferative capacity of the cells subjected to cyclic strain compared with cells maintained under static conditions. The flexed cells also exhibited upregulation of the chondrocytic gene markers type II collagen and aggrecan. In addition, cyclic strain resulted in increased expression of the alpha2 and alpha5 integrin subunits, as well as an increased expression of vimentin. There was also intracellular reconfiguration of the enzyme protein kinase C. Our findings suggest that these molecules may play a role in the signal transduction pathway, eliciting cellular response to mechanical stimulation.
Division of Arthritis Surgery, Department of Orthopaedic Surgery, Johns Hopkins University, The Good Samaritan Hospital, Baltimore, Maryland 21239, USA.
Kian
K
Lahiji
Anna
A
Polotsky
David S
DS
Hungerford
Carmelita G
CG
Frondoza
D000368:Aged; D053674:Aggrecans; D019645:Arthroplasty, Replacement, Knee; D002358:Cartilage, Articular / Q000166:cytology*; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005819:Genetic Markers / Q000187:drug effects*; D006801:Humans; D039421:Integrin alpha2 / Q000378:metabolism*; D039482:Integrin alpha5 / Q000378:metabolism*; D037181:Lectins, C-Type; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012825:Silicon; D013314:Stress, Mechanical; D015854:Up-Regulation; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
D053674:Aggrecans; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D005819:Genetic Markers; D039421:Integrin alpha2; D039482:Integrin alpha5; D037181:Lectins, C-Type; D011509:Proteoglycans; D014746:Vimentin; D011493:Protein Kinase C; D012825:Silicon