Dynamic compression alters the chondrogenic phenotypes of human osteoarthritis chondrocytes

Abstract

Osteoarthritis (OA) is a disabling disease that a rapidly growing threat to the health of populations worldwide. Although the etiology of OA is unknown, it is generally believed that mechanical factor may contribute to alter matrix degradation possibly leading to OA. Cellular reactions of OA chondrocytes (OACs) are very pronounced. Major phenotypic changes of OACs consist of reduced expression for the chondrogenic markers such as SOX9 and COL2A1 and elevated synthesis of matrix degradation enzymes accelerating matrix degradation. In this study, we utilize our well-established microencapsulation platform to investigate whether compression loading of human OACs in a collagen construct has any beneficial effects in terms of resuming their chondrogenic phenotypes. Using in-vitro model and state-of-the art technology, we characterize the major chondrogenic markers and cell matrix interaction molecules. Upon 3-hours dynamic compression for a duration of up to 7 days, SOX9 expression is consistently induced in both cytoplasm and co-localized with nucleus on day 1 and day 7 suggesting activation of this transcription factor. Additionally, the compression loading reduces MMP1 and MMP13 expressions as well as subsequent collagen matrix degradation. This work provides important insights on understanding the mechanical stimulation of human OACs and hence future development of stimulatory regimes for human OACs.