TY  - JOUR
TI  - Modulation of limb bud chondrogenesis by retinoic acid and retinoic acid receptors.
AU  - Jiang, H
AU  - Soprano, D R
AU  - Li, S W
AU  - Soprano, K J
AU  - Penner, J D
AU  - Gyda, M
AU  - Kochhar, D M
T2  - The International Journal of Developmental Biology
AB  - An excess of retinoic acid (RA) in the mouse embryo in utero produces hypochondrogenesis and severe limb bone deformities. Since one of the RA receptors--RAR-beta 2, is specifically induced in the limb bud cells upon treatment of embryos with teratogenic doses of RA, we investigated if this receptor played a role in teratogenesis by regulating the process of chondrogenesis. In micromass cultures of mouse limb bud mesenchymal cells, we found that a downregulation of RAR-beta 2 as well as several other RAR isoforms by supplementation of the culture medium with specific oligodeoxynucleotides stimulated chondrogenesis: cartilage nodule number, sulfated proteoglycans, and synthesis of collagen type IIB were all enhanced in a dose-dependent manner. However, only the antisense RAR-beta 2 probe efficiently prevented the strong inhibitory effects of exogenous RA on chondrogenesis in these cells. The data suggest that the RAR-RA complexes play a role in position-dependent patterning of the limb skeleton in normal development and that, in particular, RAR-beta 2 serves to prevent the mesenchymal cells from expressing their chondrogenic bias. Our results further strengthen the argument that RA-dependent elevation in RAR-beta 2 levels plays a unique role in RA-induced teratogenesis.
PY  - 1995
VL  - 39
IS  - 4
SP  - 617
EP  - 627
J2  - Int. J. Dev. Biol.
LA  - en
SN  - 0214-6282
SN  - 1696-3547
UR  - https://ijdb.ehu.eus/article/8619960
Y2  - 2024/11/22/04:22:59
ER  -