Effect Of L-Carnitine On Expression Of OPG And RANKL In Murine MC3T3-E1 Osteoblastic Cells And The Ovariectotomized Rats Model

Objectives:To characterize the efects of L-Carnitine on the expression of osteoprotegerin and receptor activator of nuclear factor-κB ligand in murine MC3T3-E1 osteoblastic cells and the ovariectotomized Rats model in order to elucidate it's molecular mechanism in the prevention and treatment of postmenopausal osteoporosis.Methods:(1) Murine MC3T3-E1 osteoblastic cells lines were used in this study to investigate the expression of OPG protein by Western blot after they were treatment with 0.1-10mM concentration of L-Carnitine for 24h.(2) The adult ovariectomized rat (OVX) models with osteoporosis were used to investigate the changes of isolated lumbar vertebrae and right femur bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) with and without the treatment of L-Carnitine. The level of serum OPG and RANKL and the expressions of OPG and RANKL protein in the distal femur were detected by enzyme-linked immunsorbent assay (ELISA) method and immunohistochemistry, respectively.Results:(1) Treatment with 0.1-10mM concentration of L-Carnitine to MC3T3-E1 osteoblastic cells caused a dose-dependent increase in the expression of OPG protein. After 6-24h of treatment, L-Carnitine at 10mM increased OPG protein production in cultures of MC3T3-E1 osteoblastic cells in a time-dependent manner.(2) Compared with the SHAM group, BMD of isolated lumbar vertebrae and right distal femur had significant decreased in the OVX group. The level of serum OPG and the expression of OPG in the distal femur were significantly reduced, while RANKL was significantly inceased. With the treatment of L-Carnitine, BMD was inereased remarkably compared with the OVX group. While OPG was elevated and RANKL was decreased in the LC+OVX group, there was significant difference.Conclusions:(1) A direct action of L-Carnitine on MC3T3-E1 osteoblastic cells may be mediated by up-regulated OPG production in a dose-and time-dependent manner.(2) L-Carnitine may increase BMD of isolated lumbar vertebrae and right distal femur in OVX rat.(3) L-Carnitine can up-regulate OPG/RANKL ratio in serum and femur in OVX rat.