Retinoic acid suppresses the osteogenic differentiation capacity of murine osteoblast-like 3/A/1D-1M cell cultures.
Bone is a target tissue for action of retinoids though their precise role remains unclear. This study investigated the effects of retinoic acid (RA) on the marrow stromal 3/A/1D-1M osteoblast-like cells, derived from the in vivo transplantation of 3/A/1D-1 chondroprogenitor cells. Long-term treatment with 1 microM RA for 7 weeks induced a marked decrease in bone-like nodule number and ultrastructural alterations in the striation and the size of the collagen fibres. RA at concentrations varying from 10 nM to 3.16 microM had a dose-dependent inhibition effect on alkaline phosphatase (AP) activity with an IC50 of 0.7 microM. Treatment with 1 microM RA for up to 17 days induced a time-dependent inhibition of AP activity, while the beginning of RA treatment (4 or 52 h of culture) produced a differential magnitude of inhibition. These variations were unrelated to modifications of the expression of RAR receptor at the protein level, as assessed by Western blot analysis. Exposure to 1 microM RA for 6 or 24 h administered at day 14 produced an inhibition of AP activity, which reached a maximum after 48 h, with a recovery time of 8 days in both cases. Long-term treatment with RA at 1 microM completely abolished the level of osteocalcin mRNA on both days 12 and 16, as revealed by Northern blot analysis. However, such RA-treated cells retained the constitutive expression of type II procollagen transcripts. These results suggest that RA inhibits several aspects of osteogenic differentiation capacity, a loss of phenotype, which, in association with the maintenance of type II procollagen cartilage-related characteristic, could be a prerequisite step for cellular plasticity.
Laboratoire de Biologie-Odontologie, Université Paris, Institut Biomédical des Cordeliers, France.
A
A
Cohen-Tanugi
N
N
Forest
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000096:biosynthesis; D011347:Procollagen / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011347:Procollagen; D012333:RNA, Messenger; D015675:Osteocalcin; D014212:Tretinoin; D000469:Alkaline Phosphatase