Role of Cyp26b1 in endochondral bone formation

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Retinoic acid (RA) plays important roles in embryonic development. CYP26 enzymes, which degrade RA, have specific expression patterns and produce a RA gradient. RA gradient regulates the patterning of the various structures in embryos. However, it has not been addressed whether a RA gradient also exists in organs after birth.We found localized RA activities within the growth plate in juvenile mice. Cyp26b1 was specifically expressed in proliferative chondrocytes of the growth plate cartilage. The mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1 cKO) showed retardation of bone growth in the juvenile stage. Their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities. These results suggest that the RA distribution within the growth plate is responsible for the normal function of the growth plate and growing bones in juveniles.