Abstract
Summary Statement
In articular cartilage defects, chemokines are upregulated and potentially induce the migration of bone marrow cells to accelerate the healing processes.
Introduction
The treatment of damaged articular cartilages is one of the most challenging issues in sports medicine and in aging societies. In the microfracture technique for the treatment of articular cartilage defects, bone marrow cells are assumed to migrate from the bone marrow. Bone marrow cells are well-known for playing crucial roles in the healing processes, but how they can migrate from underlying bone marrow remains to be investigated. We have previously shown that SDF-1, one of chemokines, play crucial roles in the recruitment of mesenchymal stem cells in bone healing processes, and the induction of SDF-1 can induce a successful bone repair. If the migration can be stimulated by any means in the cartilage defects, a better result can be expected. The aim of this study was to elucidate the mechanisms of the migration of bone marrow cells and which factors contribute to the processes.
Materials & Methods
Articular cartilage defects of 2 mm of diameter were created by drilling the cartilage with a wire to just the subchondral bone in 5-week-old SD rats. The width and depth of the created defects were confirmed by HE staining in histology. The healing tissues were harvested at days 2, 6, and 14 after the operation, and total RNAs were entracted. PCR array was conducted according to the manufacturer's instruction. Quantitative PCR (qPCR) was performed using cDNA of the healing tissues. Bone marrow cells were harvested from 5-week-old SD rat, and a standard migration assay was performed using chemokines.
Results
CCL2, CCL3, CCL7 and CCL12 were upregulated in the healing tissues of cartilage defects shown by PCR array. The expression pattterns were confirmed by an expression analysis by qPCR. Both CCL2 and CCL3 induced the migration of bone marrow cells in the in vitro migration assay.
Discussion/Conclusion
This study showed for the first time that CCL chemokines are upregulated in the articular cartilage defects and induce the migration of bone marrow cells. These results lead to an innovative measures along with an appropriate delivery method in induction the migration of bone marrow cells from the underlying bone marrow to stimulate articular cartilage healing processes.
