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Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts

Thomas, Gethin P; Baker, S U LU ; Eisman, J. A. and Gardiner, Michael E. (2001) In Journal of Endocrinology 170(2). p.60-451
Abstract

Osteoblast-osteoclast coordination is critical in the maintenance of skeletal integrity. The modulation of osteoclastogenesis by immature cells of the osteoblastic lineage is mediated through receptor activator of NF kappa B (RANK), its ligand RANKL, and osteoprotegerin (OPG), a natural decoy receptor for RANKL. Here, the expression of OPG and RANKL in primary mouse osteoblastic cultures was investigated to determine whether the osteoclastogenic stimulus depended on the stage of osteoblastic differentiation and the presence of the calciotrophic hormone 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)). OPG mRNA expression was increased in osteoblastic cultures after the onset of mineralisation relative to less mature cultures, but did not... (More)

Osteoblast-osteoclast coordination is critical in the maintenance of skeletal integrity. The modulation of osteoclastogenesis by immature cells of the osteoblastic lineage is mediated through receptor activator of NF kappa B (RANK), its ligand RANKL, and osteoprotegerin (OPG), a natural decoy receptor for RANKL. Here, the expression of OPG and RANKL in primary mouse osteoblastic cultures was investigated to determine whether the osteoclastogenic stimulus depended on the stage of osteoblastic differentiation and the presence of the calciotrophic hormone 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)). OPG mRNA expression was increased in osteoblastic cultures after the onset of mineralisation relative to less mature cultures, but did not alter in response to 1,25-(OH)(2)D(3) treatment. In contrast, basal RANK L mRNA expression did not change during differentiation but was significantly enhanced by 1,25-(OH)(2)D(3) treatment at all times. The stimulatory effects of 1,25-(OH)(2)D(3) on RANKL were lessened in more mature cultures, however. The RANKL/OPG ratio, an index of osteoclastogenic stimulus, was therefore increased by 1,25-(OH)(2)D(3) treatment at all stages of osteoblastic differentiation, but to a lesser degree in cultures after the onset of mineralisation. Thus the 1,25-(OH)(2)D(3)-driven increase in osteoclastogenic potential of immature osteoblasts appears to be mediated by increased RANKL mRNA expression, with mature osteoblasts having relatively decreased osteoclastogenic activity due to increased OPG mRNA expression. These findings suggest a possible mechanism for the recently proposed negative regulatory role of mature osteoblasts on osteoclastogenesis and indicate that the relative proportions of immature and mature osteoblasts in the local microenvironment may control the degree of resorption at each specific bone site.

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publication status
published
keywords
Analysis of Variance, Animals, Calcitriol, Carrier Proteins, Cell Differentiation, Cells, Cultured, Gene Expression, Glycoproteins, Membrane Glycoproteins, Mice, Mice, Inbred Strains, Osteoblasts, Osteoprotegerin, RANK Ligand, RNA, Messenger, Receptor Activator of Nuclear Factor-kappa B, Receptors, Cytoplasmic and Nuclear, Receptors, Tumor Necrosis Factor, Reverse Transcriptase Polymerase Chain Reaction, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.
in
Journal of Endocrinology
volume
170
issue
2
pages
10 pages
publisher
Society for Endocrinology
external identifiers
  • scopus:0034882731
ISSN
0022-0795
DOI
language
English
LU publication?
no
id
c79708e0-940f-4c3e-b7c3-e6691859f3bb
date added to LUP
2017-03-09 15:04:32
date last changed
2018-05-29 09:55:39
@article{c79708e0-940f-4c3e-b7c3-e6691859f3bb,
  abstract     = {<p>Osteoblast-osteoclast coordination is critical in the maintenance of skeletal integrity. The modulation of osteoclastogenesis by immature cells of the osteoblastic lineage is mediated through receptor activator of NF kappa B (RANK), its ligand RANKL, and osteoprotegerin (OPG), a natural decoy receptor for RANKL. Here, the expression of OPG and RANKL in primary mouse osteoblastic cultures was investigated to determine whether the osteoclastogenic stimulus depended on the stage of osteoblastic differentiation and the presence of the calciotrophic hormone 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)). OPG mRNA expression was increased in osteoblastic cultures after the onset of mineralisation relative to less mature cultures, but did not alter in response to 1,25-(OH)(2)D(3) treatment. In contrast, basal RANK L mRNA expression did not change during differentiation but was significantly enhanced by 1,25-(OH)(2)D(3) treatment at all times. The stimulatory effects of 1,25-(OH)(2)D(3) on RANKL were lessened in more mature cultures, however. The RANKL/OPG ratio, an index of osteoclastogenic stimulus, was therefore increased by 1,25-(OH)(2)D(3) treatment at all stages of osteoblastic differentiation, but to a lesser degree in cultures after the onset of mineralisation. Thus the 1,25-(OH)(2)D(3)-driven increase in osteoclastogenic potential of immature osteoblasts appears to be mediated by increased RANKL mRNA expression, with mature osteoblasts having relatively decreased osteoclastogenic activity due to increased OPG mRNA expression. These findings suggest a possible mechanism for the recently proposed negative regulatory role of mature osteoblasts on osteoclastogenesis and indicate that the relative proportions of immature and mature osteoblasts in the local microenvironment may control the degree of resorption at each specific bone site.</p>},
  author       = {Thomas, Gethin P and Baker, S U and Eisman, J. A. and Gardiner, Michael E.},
  issn         = {0022-0795},
  keyword      = {Analysis of Variance,Animals,Calcitriol,Carrier Proteins,Cell Differentiation,Cells, Cultured,Gene Expression,Glycoproteins,Membrane Glycoproteins,Mice,Mice, Inbred Strains,Osteoblasts,Osteoprotegerin,RANK Ligand,RNA, Messenger,Receptor Activator of Nuclear Factor-kappa B,Receptors, Cytoplasmic and Nuclear,Receptors, Tumor Necrosis Factor,Reverse Transcriptase Polymerase Chain Reaction,Journal Article,Research Support, Non-U.S. Gov't,Research Support, U.S. Gov't, P.H.S.},
  language     = {eng},
  number       = {2},
  pages        = {60--451},
  publisher    = {Society for Endocrinology},
  series       = {Journal of Endocrinology},
  title        = {Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts},
  url          = {http://dx.doi.org/},
  volume       = {170},
  year         = {2001},
}