Document Detail

Encapsulation of Chondrocytes in High-Stiffness Agarose Microenvironments for In Vitro Modeling of Osteoarthritis Mechanotransduction.
MedLine Citation:
PMID:  25395215     Owner:  NLM     Status:  Publisher    
In articular cartilage, chondrocytes reside within a gel-like pericellular matrix (PCM). This matrix provides a mechanical link through which joint loads are transmitted to chondrocytes. The stiffness of the PCM decreases in the most common degenerative joint disease, osteoarthritis. To develop a system for modeling the stiffness of both the healthy and osteoarthritic PCM, we determined the concentration-stiffness relationships for agarose. We extended these results to encapsulate chondrocytes in agarose of physiological stiffness. Finally, we assessed the relevance of stiffness for chondrocyte mechanotransduction by examining the biological response to mechanical loading for cells encapsulated in low- and high-stiffness gels. We achieved agarose equilibrium stiffness values as large as 51.3 kPa. At 4.0% agarose, we found equilibrium moduli of 34.3 ± 1.65 kPa, and at 4.5% agarose, we found equilibrium moduli of 35.7 ± 0.95 kPa. Cyclical tests found complex moduli of ~100-300 kPa. Viability was >96% for all studies. We observed distinct metabolomic responses in >500 functional small molecules describing changes in cell physiology, between primary human chondrocytes encapsulated in 2.0 and 4.5% agarose indicating that the gel stiffness affects cellular mechanotransduction. These data demonstrate both the feasibility of modeling the chondrocyte pericellular matrix stiffness and the importance of the physiological pericellular stiffness for understanding chondrocyte mechanotransduction.
Aaron A Jutila; Donald L Zignego; William J Schell; Ronald K June
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-14
Journal Detail:
Title:  Annals of biomedical engineering     Volume:  -     ISSN:  1573-9686     ISO Abbreviation:  Ann Biomed Eng     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-14     Completed Date:  -     Revised Date:  2014-11-15    
Medline Journal Info:
Nlm Unique ID:  0361512     Medline TA:  Ann Biomed Eng     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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