Stroma-derived Factor Alpha (SDF-1α) In Bone Disease In Multiple Myeloma

Objective:To study the relationship between development of myeloma bone disease and stromal cell-derived factor1alpha (SDF-1α) in order to explore potential target of myeloma bone disease. Methods:To measure SDF-la level in blood plasma and bone marrow plasma of myeloma patients and controls by ELISA. To testify expression of CXCR4(CD184), specific ligand of SDF-1α, on myeloma cells by flow cytometry and evaluate the relationship of CXCR4expression and severity of myeloma bone disease. To culture peripheral blood mononuclear cells (PBMC) into mature osteoclasts in vitro and study whether SDF-1α stimulates osteoclastgenesis. To induce bone marrow stromal cells into osteoblasts and study whether SDF-la affects secretion of alkaline phosphatase (ALP) by osteoblasts. Results:SDF-1α level in bone marrow plasma was significantly higher than that in blood plasma (P<0.05). There was a high proportion of CXCR4expression on MM patients with severe bone disease. After culture for12days, SDF-la significantly enhanced form of osteoclasts (P<0.05). Specific inhibitor of CXCR4, AMD3100, dramatically inhibited osteoclast maturation. Yet, ALP level was not affected by SDF-la. Conclusion:SDF-1α level was higher in bone marrow than in peripheral blood in MM patients. Most myeloma cells expressed CXCR4, whose intensity paralleled the severity of bone disease. SDF-1a stimulated osteoclastgenesis, but not ALP synthesis by osteoblasts。 Blocking SDF-1/CXCR4might be a potential strategy for the treatment of myeloma bone disease.