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Mandibular coronoid process in parathyroid hormone-related protein-deficient mice shows ectopic cartilage formation accompanied by abnormal bone modeling

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Abstract

Parathyroid hormone-related protein (PTHrP) null mutant mice were analyzed to investigate an additional role for PTHrP in cell differentiation. We found ectopic cartilage formation in the mandibular coronoid process in newborn mice. While many previous studies involving PTHrP gene knockout mouse have shown that the cartilage in various regions becomes smaller, this is the first report showing an "increase" of cartilage volume. Investigations of mandibular growth using normal mice indicated that coronoid secondary cartilage never formed from E 15 to d 4, but small amount of cartilage temporally formed at d 7, and this also applies to PTHrP-wild type mice. Therefore, PTHrP deficiency consequently advanced the secondary cartilage formation, which is a novel role of PTHrP in chondrocyte differentiation. In situ hybridization of matrix proteins showed that this coronoid cartilage had characteristics of the lower hypertrophic cell zone usually present at the site of endochondral bone formation and/or "chondroid bone" occasionally found in distraction osteogenesis. In addition, the coronoid process in the PTHrP-deficient mouse also showed abnormal expansion of bone marrow and an increase in the number of multinucleated osteoclasts, an indication of abnormal bone modeling. These results indicate that PTHrP is involved in bone modeling as well as in chondrocyte differentiation. In situ hybridization of matrix protein mRNAs in the abnormal mandibular condylar cartilage revealed that this cartilage was proportionally smaller, supporting previous immunohistochemical results.

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Acknowledgements

The monoclonal antibody 12/21/1C6 developed by B. Caterson (Connective Tissue Biology Lab, School of Molecular and Medical Biosciences) were obtained from the Developmental Studies Hybridoma Bank maintained by the University of Iowa, Department of Biological Sciences, Iowa City, IA 52242, under contact NO1-HD-&-3263 from the NICHD. This work is supported by Grant-in-Aid for Scientific Research (No. 12671762) from Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Maxillofacial Anatomy, Department of Maxillofacial Biology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan

    Shunichi Shibata & Yasuo Yamashita

  2. Maxillofacial Orthognatics, Department of Maxillofacial Reconstruction and Function, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan

    Naoto Suda, Kenji Fukada & Kimie Ohyama

  3. Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, 3052, Parkville, Victoria, Australia

    Vicki E. Hammond

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  1. Shunichi Shibata
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  2. Naoto Suda
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  3. Kenji Fukada
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  4. Kimie Ohyama
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  5. Yasuo Yamashita
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  6. Vicki E. Hammond
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Correspondence to Shunichi Shibata.

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Shibata, S., Suda, N., Fukada, K. et al. Mandibular coronoid process in parathyroid hormone-related protein-deficient mice shows ectopic cartilage formation accompanied by abnormal bone modeling. Anat Embryol 207, 35–44 (2003). https://doi.org/10.1007/s00429-003-0325-6

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