Abstract
Osteoarthritis (OA) affects millions of people and is the fastest growing cause of disability worldwide. In order to address this burden, early intervention strategies have been proposed. Therapies that utilise bone marrow stromal cells (BM-MSCs) to induce cartilage repair, either as a cell therapy or by endogenous release by drilling or microfracture, have proved promising. However, limitations include fibrotic features of the regenerated cartilage that may affect mechanical properties and therefore the longevity of such a repair. In order to improve this regenerative technique, further research is required to understand the key players in the repair mechanism. An interaction, which may be important, is that between BM-MSCs and the resident chondrocytes. The aim of this study is to understand the interplay between BM-MSC and resident chondrocytesisolated from different zonal locations within the human knee.
We compared chondrocytes from three different cartilage areas: chondrocytes from 1) the superficial zone (SZ) and 2) the middle-deep (MDZ) zone of non-weight bearing femoral condyles, and from 3) the osteoarthritic zone (OAZ) of patients undergoing knee replacement. First, we evaluated the influence of different chondrocytes on BM-MSCs monolayer in a transwell co-culture, assessing transcript levels of early chondrogenic markers including Sox9 and Col1. Secondly, in a 3D co-culture system, we evaluated how cartilage chips from the three different zones affect the chondrogenic differentiation of BM-MSC pellets. Results indicated that cells from the SZ induce chondrogenic differentiation of BM-MSCs when co-cultured. In contrast, MDZ and OAZ have a negative effect, compared to control conditions. Our findings suggest that chondrocytes from the SZ, a zone which has been reported to reduce with age and may be lost in advanced OA, is important to direct BM-MSCs differentiation towards the chondrogenic fate. This may be relevant to cartilage repair strategies.
