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Title: Cyp26b1 within the growth plate regulates bone growth in juvenile mice

Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1{sup Δchon} cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focallymore » by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone.« less
Authors:
 [1] ;  [2] ;  [2] ;  [3] ;  [2] ;  [1] ;  [4] ;  [5] ;  [3] ;  [1] ;  [2]
  1. Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan)
  2. (Japan)
  3. Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)
  4. Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagito, Gifu 501-1194 (Japan)
  5. Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)
Publication Date:
OSTI Identifier:
22416818
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 454; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARTILAGE; CELL PROLIFERATION; CUMULATIVE RADIATION EFFECTS; EMBRYOS; ENZYMES; JUVENILES; MICE; ONTOGENESIS; PARTURITION; PLATES; RETINOIC ACID; SKELETON; VITAMIN A