In:
Journal of Bone and Mineral Research, Wiley, Vol. 17, No. 1 ( 2002-01), p. 91-100
Abstract:
Retinoids are known to be of special importance for normal bone growth and development. Recently, we reported that retinoids not only induced osteoblast differentiation, but also inhibited osteoclast formation in vitro. In this study, we examined the osteogenic effects of geranylgeranoic acid (GGA), a chemically synthesized acyclic retinoid, in bone in vitro and in vivo. GGA not only suppressed proliferation of osteoblastic MC3T3‐E1 cells, but also up‐regulated differentiation markers of osteoblasts such as alkaline phosphatase (ALP) activity and expression of osteopontin (OP) messenger RNA (mRNA). In contrast, GGA inhibited osteoclast formation induced by 1α,25‐dihydroxyvitamin D 3 [1α,25(OH) 2 D 3 ] in cocultures of mouse bone marrow cells and primary osteoblasts. Treatment of stromal ST2 cells with GGA restored the 1α,25(OH) 2 D 3 ‐ or prostaglandin E 2 (PGE 2 )‐induced suppression of osteoprotegerin (OPG) mRNA expression. GGA inhibited osteoclast formation induced by macrophage colony‐stimulating factor (M‐CSF) and soluble receptor activator of nuclear factor κB ligand (sRANKL) in the culture of bone marrow macrophages. Thus, it is likely that GGA inhibits osteoclast formation by affecting both osteoblasts and osteoclast progenitors in the coculture system. Furthermore, in vivo, GGA increased bone mineral density (BMD) of total as well as distal femur in a P6 strain of senescence‐accelerated mice (SAMP6). These results indicate that GGA increases bone mass by maintaining a positive balance of bone turnover by inducing osteoblast differentiation and suppressing osteoclast formation.
Type of Medium:
Online Resource
ISSN:
0884-0431
,
1523-4681
DOI:
10.1359/jbmr.2002.17.1.91
Language:
English
Publisher:
Wiley
Publication Date:
2002
detail.hit.zdb_id:
2008867-X
