Retinoic acid suppresses the osteogenic differentiation capacity of murine osteoblast-like 3/A/1D-1M cell cultures

Differentiation. 1998 Jul;63(3):115-23. doi: 10.1046/j.1432-0436.1998.6330115.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Mice
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Osteocalcin / biosynthesis
  • Procollagen / biosynthesis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tretinoin / pharmacology*


  • Antineoplastic Agents
  • Procollagen
  • RNA, Messenger
  • Osteocalcin
  • Tretinoin
  • Alkaline Phosphatase