title: Changes in RANKL/OPG/RANK gene expression in peripheral mononuclear cells following treatment with estrogen or raloxifene.
abstract: The RANKL/OPG/RANK pathway is the key mediator of osteoclastogenesis. Mononuclear cells may be implicated in post-menopausal osteoporosis. The effect of estrogen or raloxifene on bone resorption and the expression of RANKL/OPG/RANK in peripheral blood mononuclear cells (PBMCs) was examined. Twenty-nine women with post-menopausal osteoporosis were treated with estrogen (HRT) or raloxifene for 12 months. Bone mineral density (BMD) was measured at baseline and at 12 months at the spine and hip. Serum C-terminal telopeptide (CTX) and OPG were measured at baseline and at 1, 3, 6 and 12 months. PBMCs were isolated from 17 women and changes in RANKL, OPG and RANK mRNA were determined. The effects of estrogen or raloxifene in PBMCs in vitro were also assessed. BMD increased following treatment (lumbar spine % change mean [S.E.M.]: 4.3% [0.9], p<0.001). Serum CTX decreased (6 months: -43.7% [6.0], p<0.0001). Serum OPG declined gradually (12 months: -26.4% [4.4], p<0.001). RANKL, OPG and RANK gene expression decreased (6 months: RANKL 50.0% [24.8] p<0.001, OPG: 21.7% [28] p<0.001, RANK: 76.6% [10.2] p=0.015). Changes in OPG mRNA correlated with changes in BMD (r=-0.53, p=0.027) and CTX (r=0.7, p=0.0044). Down-regulation in RANKL, OPG, RANK mRNA and reduction in bone resorption was also seen in vitro. These results suggest that the expression of RANKL/OPG/RANK in PBMCs are responsive to the slowing in bone turnover/remodeling associated with treatment with estrogen or raloxifene. Further confirmatory studies are needed.
authors: Department of Chemical Pathology, 5th Floor, North Wing, St. Thoma' Hospital, Lambeth Palace Road, London SE 1 7 EH, UK.
authors: A
authors: A
authors: Bashir
authors: Y T
authors: YT
authors: Mak
authors: S
authors: S
authors: Sankaralingam
authors: J
authors: J
authors: Cheung
authors: N W A
authors: NW
authors: McGowan
authors: A E
authors: AE
authors: Grigoriadis
authors: I
authors: I
authors: Fogelman
authors: G
authors: G
authors: Hampson
mesh_terms: D000368:Aged; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy; D002352:Carrier Proteins / Q000235:genetics*; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006023:Glycoproteins / Q000097:blood / Q000235:genetics*; D020249:Hormone Replacement Therapy; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008137:Longitudinal Studies; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy; D053244:Osteoprotegerin; D010455:Peptides / Q000097:blood; D017698:Postmenopause; D053245:RANK Ligand; D012333:RNA, Messenger / Q000097:blood; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000235:genetics*; D020845:Selective Estrogen Receptor Modulators
chemical_list: D002352:Carrier Proteins; D024042:Collagen Type I; D004967:Estrogens; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D010455:Peptides; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D020845:Selective Estrogen Receptor Modulators; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C052929:collagen type I trimeric cross-linked peptide; D020849:Raloxifene Hydrochloride; D003094:Collagen