Role And Mechanism Of CXCL12(SDF –1)secreted By Osteoclasts In The BMSCs Migration And Osteogenetic Differentiation

Periodontal disease is a serious threat to human oral health and multiple common diseases,the pathological changes in periodontal tissue cause chronic infection and leads to a substantial absorption of alveolar bone,it is the main cause of tooth loss. Routin treatment is invalid now,a new way of treatment is urgently needed. Large numbers of experiments affirmed that in the process of alveolar bone absorption caused by periodontitis, pluripotent stem cells can be chemotactic and focused to the lesion site,then differentiation into osteoblasts stimulated by periodontal local micro environment, to promote the injury repair and disease treatment.Currently the treatment of periodontitis in clinical focuse on scaling,root planning,and systemic antibiotics. But recently,some scholars believe that the bone marrow mesenchymal stem cells is another kind of pluripotent stem cells beside hematopoietic stem cells, has the advantages in hard tissue injury repair. Under certain conditions, BMSCs can differentiate into osteoblasts, fibroblasts, adipose cell, odontoblast cells and epithelial cells. Therefor e, BMSCs provide an important source of stem cells for the treatment of periodontitis bone difect.Bone resorption is the result of synergistic effect by multi cell. The stem cells gathered to the surface of bone absorption and differentiation is the main link of the bone repair. Osteoclast play a major role in bone resorption regulated by cytokines RANKL and M-CSF. The osteoclasts and osteoblasts as the key cells of the bone remodelin g process, leading the coupling,balance process between bone resorption and bone formation. The main form is osteoclasts constantly degradation the old bone while osteoblasts construct new bone in the same location.Previous studies mainly focused on differentiation and activation mechanism of osteoblast and osteoclast, how Osteoclast or activated osteoclast influence to the BMSCs is less well studied.Based on the above analysis,this paper firstly establish a method of isolation and culture of BMSCs、osteoclasts. Study on how osteoclasts effect BMSCs migration through the chemokine secretion;to understand the effect of osteoclasts on the numbers of BMSCs migration. Then use vitro culture model of bone absorption,observe the BMSCs migration during bone resorption caused by osteoclast. Finally, test the effect of CXCL12 on BMSCs differentiation. To provide the experimental basis of CXCL12 signal factor help the treatment of periodontitis bone defect.The main research results and conclusions are as follows:1、Using adherence method to isolate the BMSCs cells from the bone marrow cells,BMSCs has strong ability to proliferate, BMSCs also have potential ability to differentiat into osteoblasts, adipocytes, chondrocytes. It is the first choice of mesenchymal stem cells.2、 Using differential adherent ability to isolated mononuclear cells from bone marrow. By the use of growth factors RANKL and M-CSF to obtain quantity, activity, strong bone resorption ability osteoclasts, lays the foundation for the establishment of osteoclastic bone resorption model.3、Osteoclasts secrete higher levels of CXCL12 in vitro, can effectively induce BMSCs migration,Inhibition CXCL12 synthesis can significantly reduce the migration ability of BMSCs, but there are still some of the BMSCs migrated by induction. Therefore, the osteoclasts secrete many kinds of cytokine induced BMSCs migration, CXCL12 factors play an important role in the induction process.4、In the process of bone absorption, osteoclast release large amounts of CXCL12 factor induced BMSCs migration to the bone defect, CXCL12 inhibit the BMSCs capability of osteogenic differentiation.