OSTEOPROTEGERIN GENE EXPRESSION IN MULTIPLE MYELOMA PATIENTS

Abstract

Osteoprotegerin (OPG) is a novel secreted member of tumor necrosis factor receptor superfamily mainly secreted by marrow stromal cells. In vitro, Osteoclast formation can be inhibited by OPG in a dose-dependent manner. Multiple myeloma (MM) is a hematologic malignancy characterized by accumulation of plasma cells in the bone marrow (BM). Bone destruction is a complication of the disease and is usually associated with severe morbidity. The present study aimed to examine the expression of OPG at the serum protein level as well as the mRNA level in multiple myelomas (MM) in relation to the clinicopathological findings. Thirty five patients with Multiple Myeloma (MM) and 20 healthy subjects of matched age and sex were studied. Patients were subjected to complete clinical  xamination and laboratory investigations including protein electrophoresis to calculate monoclonal protein, Haemoglobin (Hb), Blood urea and serum level of B2 microglobulin (B2M).OPG concentration was estimated in serum by ELISA. A reverse transcriptase-polymerase
chain reaction (RT-PCR) was used to investigate the expression of OPG m RNA. OPG concentration in sera of MM cases was lower than normal controls (mean value 0.10 versus 0.15 ng/ml) this difference was statistically highly significant (P=0.001). Bone Marrow aspirates were taken from patients (n=10) as well as controls (n=5) where, the OPG m RNA was expressed in MM Patients by the mean of 0.7± 0.5 fold while in the controls it was 4.5±1.1 fold increase in the intensity of expression (P=0.02).A highly positive significant correlation was found between serum OPG protein level and OPG m RNA expression in BM of MM patients and controls (r=0.12, p=0.01-r=0.98, p=0.002) respectively. It is concluded that OPG expression is reduced in bone marrow specimens from myeloma patients. The adhesive interactions of myeloma cells with bone marrow stromal cells inhibit OPG production both at the m RNA and Protein level. Down regulation of OPG expression in MM patients may be involved in pathogenesis of Myeloma bone disease and may provide a useful tool for prognosis.