J. Chen et al., REGULATION OF BONE SIALOPROTEIN AND OSTEOPONTIN MESSENGER-RNA EXPRESSION BY DEXAMETHASONE AND 1,25-DIHYDROXYVITAMIN-D-3 IN RAT BONE ORGAN-CULTURES, Connective tissue research, 34(1), 1996, pp. 41
Bone sialoprotein (BSP) and osteopontin (OPN) are prominent components
of the extracellular matrix of mineralized connective tissues that ha
ve been implicated in the formation and remodelling of bone. Although
these proteins have similar biochemical properties and are expressed b
y bone cells during bone formation it has been suggested that they hav
e different functions and that their expression is regulated independe
ntly by hormones and cytokines. The precise role of these proteins has
, however, yet to be firmly established. Since steroid hormones strong
ly influence the formation of bone we have analyzed the effects of glu
cocorticoids and 1,25 dihydroxyvitamin D-3 (1,25-(OH)(2)D-3) on the ex
pression of BSP and OPN mRNAs in developing rat bone in vitro using in
situ hybridization. In these studies it has been possible to identify
the nature and spatial distribution of the cells that respond to thes
e hormones by changes in sialoprotein expression. When cultured in the
presence of the synthetic glucocorticoid, dexamethasone (dex), expres
sion of BSP was increased >5-fold in osteoblastic cells of the primary
spongiosa in the tibial growth plate, in the mandibular bone and in c
alvarial bone. In addition, expression of BSP mRNA by hypertrophic car
tilage cells in the was dramatically increased as were the number of r
esponding cells indicating that glucocorticoids promote differentiatio
n of hypertrophic cartilage cells as well as osteoblasts. Dexamethason
e also stimulated a marked (>5-fold) increase in OPN expression by ost
eoblasts and cells lining endosteal and periosteal bone surfaces. In c
ontrast to dex 1,25-(OH)(2)D-3 suppressed BSP expression in osteoblast
ic cells whereas OPN expression was strongly (>5-fold) stimulated in a
ll three cultured bone tissues. Histological examination of the tissue
s showed that cell viability was retained over the culture period. How
ever, in the presence of 1,25-(OH)(2)D-3 considerable resorption of th
e tissue was evident, with cement and reversal lines being prominent.
The increased expression of BSP and OPN by dex is consistent with the
stimulation of bone formation by glucocorticoids, whereas the differen
tial effects of 1,25-(OH)(2)D-3 on BSP and OPN may reflect a stimulati
on of bone remodelling.