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.