Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts

Citation
Gp. Thomas et al., Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts, J ENDOCR, 170(2), 2001, pp. 451-460
Citations number
56
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
JOURNAL OF ENDOCRINOLOGY
ISSN journal
0022-0795 → ACNP
Volume
170
Issue
2
Year of publication
2001
Pages
451 - 460
Database
ISI
SICI code
0022-0795(200108)170:2<451:CRMEID>2.0.ZU;2-0
Abstract
Osteoblast-osteoclast coordination is critical in the maintenance of skelet al integrity The modulation of osteoclastogenesis by immature cells of the osteoblastic lineage is mediated through receptor activator of NF kappaB (R ANK), its ligand RANKL, and osteoprotegerin (OPG), a natural decoy receptor for RANKL. Here, the expression of OPG and RANKL in primary mouse osteobla stic cultures was investigated to determine whether the osteoclastogenic st imulus depended on the stage of osteoblastic differentiation and the presen ce of the calciotrophic hormone 1,25-dihydroxvitamin 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 re sponse to 1,25-(OH)(2)D-3 treatment. In contrast, basal RANKL mRNA expressi on 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 b y 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 immatu re osteoblasts appears to be mediated by increased RANKL mRNA expression, w ith mature osteoblasts having relatively decreased osteoclastogenic activit y due to increased OPG mRNA expression. These findings suggest a possible m echanism for the recently proposed negative regulatory role of mature osteo blasts on osteoclastogenesis and indicate that the relative proportions of immature and mature osteoblasts in the local microenvironment may control t he degree of resorption at each specific bone site.