Serum parathyroid hormone, but not menopausal status, is associated with the expression of osteoprotegerin and RANKL mRNA in human bone samples.
OBJECTIVE
Osteoprotegerin (OPG) and its ligand 'receptor activator of NF-kB ligand' (RANKL) are important regulators of bone metabolism. RANKL, expressed in osteoblasts, activates osteoclast differentiation and osteoclast function by binding the 'receptor activator of NF-kB' (RANK), expressed in ostoclast precursors and mature osteoclasts. The effect is prevented by OPG, a soluble receptor of RANKL. In vitro studies have suggested that estrogen stimulates OPG, whereas parathyroid hormone (PTH) inhibits OPG expression and stimulates the expression of RANKL.


METHODS
In the present study, we examined the relationship between the menopause, serum PTH and the expression of OPG and RANKL in human bone tissue in vivo.


METHODS
To address this question, we established a 5'-nuclease assay to quantify the mRNA copies of human OPG and RANKL, normalized to the number of copies of beta-actin mRNA in 169 women (mean age: 52.4+/-11.6 years), who underwent surgery for early breast cancer. Intact serum PTH was measured by chemoluminescence in 61 women.


RESULTS
We found no significant difference in the expression of OPG and RANKL between postmenopausal women and premenopausal women. Also, the ratio of RANKL to OPG was unchanged in relation to the menopausal status. Serum PTH was negatively associated with the expression of OPG (r=-0.33, P=0.01), but also, surprisingly, with the expression of RANKL (r=-0.28, P=0.03).


CONCLUSIONS
We failed to observe the expected changes in the expression of OPG and RANKL in human bone samples at menopause. High in vivo levels of circulating PTH are accompanied by low levels of expression of the two transcripts in human bone tissue.
Seck
T
T
Department of Internal Medicine I, University of Heidelberg, 69115 Heidelberg, Germany. Thomas.Seck@yale.edu
Diel
I
I
Bismar
H
H
Ziegler
R
R
Pfeilschifter
J
J
D001706:Biopsy; D001842:Bone and Bones / Q000378:metabolism* / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008593:Menopause / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D008875:Middle Aged; D053244:Osteoprotegerin; D010281:Parathyroid Hormone / Q000097:blood*; D053245:RANK Ligand; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human