Abstract
IntroductionThe repair capability of traumatized articular cartilage is highly limited so that joint injuries often lead to osteoarthritis. Migratory chondrogenic progenitor cells (CPC) might represent a target cell population for in situ regeneration. This study aims to clarify, whether 1) CPC are present in regions of macroscopically intact cartilage from human osteoarthritic joints, 2) CPC migration is stimulated by single growth factors and the cocktail of factors released from traumatized cartilage and 3) CPC migration is influenced by cytokines present in traumatized joints.MethodsWe characterized the cells growing out from macroscopically intact human osteoarthritic cartilage using a panel of positive and negative surface markers and analyzed their differentiation capacity. The migratory response to platelet-derived growth factor (PDGF)-BB, insulin-like growth factor 1 (IGF-1), supernatants obtained from in vitro traumatized cartilage and interleukin-1 beta (IL-1β) as well as tumor necrosis factor alpha (TNF-α) were tested with a modified Boyden chamber assay. The influence of IL-1β and TNF-α was additionally examined by scratch assays and outgrowth experiments.ResultsA comparison of 25 quadruplicate marker combinations in CPC and bone-marrow derived mesenchymal stromal cells showed a similar expression profile. CPC cultures had the potential for adipogenic, osteogenic and chondrogenic differentiation. PDGF-BB and IGF-1, such as the supernatant from traumatized cartilage, induced a significant site-directed migratory response. IL-1β and TNF-α significantly reduced basal cell migration and abrogated the stimulative effect of the growth factors and the trauma supernatant. Both cytokines also inhibited cell migration in the scratch assay and primary outgrowth of CPC from cartilage tissue. In contrast, the cytokine IL-6, which is present in trauma supernatant, did not affect growth factor induced migration of CPC.ConclusionThese results indicate that traumatized cartilage releases chemoattractive factors for CPC but IL-1β and TNF-α inhibit their migratory activity which might contribute to the low regenerative potential of cartilage in vivo.
Highlights
The repair capability of traumatized articular cartilage is highly limited so that joint injuries often lead to osteoarthritis
In the context of cartilage repair the chemoattractive properties of platelet derived growth factor isoforms (PDGF), insulin like growth factor 1 (IGF-1), basic fibroblast growth factor, bone morphogenetic proteins (BMPs) or transforming growth factor beta 1 (TGF-b 1) for bonemarrow-derived mesenchymal stromal cells (MSC) could be of special interest [5,6,7,8,9]
Our results show that macroscopically intact osteoarthritic cartilage contains migratory cells with a chondroprogenitor phenotype and a very similar surface marker profile compared to bone-marrow-derived MSC
Summary
The repair capability of traumatized articular cartilage is highly limited so that joint injuries often lead to osteoarthritis. Traumatic injuries of articular cartilage induce pathogenetic processes like chondrocyte death, matrix degradation and release of proinflammatory mediators [1], and represent a major risk factor for the development of the autologous matrix induced chondrogenesis (AMIC), which combines microfracturing and a scaffold for ingrowth of bone-marrow-derived MSC [4]. Such an approach could possibly be enhanced by incorporation and controlled release of chemoattractive factors for MSC. In the case of partial size defects, strategies to recruit CPC from other tissue sources of a joint could be advantageous
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