Morphological Approach to Biological Action of PTHrP and Vitamin D3 on Endochondral Ossification
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- Amizuka Norio
- Division of Oral Anatomy, Niigata University Graduate School of Medical and Dental Sciences Center for Transdisciplinary Research, Niigata University
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- Henderson Janet E.
- Center for Transdisciplinary Research, Niigata University Health Centre, Royal Victoria Hospital
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- White John H.
- Department of Physiology, McGill University
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- Oda Kimimitsu
- Division of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences Center for Transdisciplinary Research, Niigata University
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- Li Minqi
- Division of Oral Anatomy, Niigata University Graduate School of Medical and Dental Sciences
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- Nozawa-Inoue Kayoko
- Division of Oral Anatomy, Niigata University Graduate School of Medical and Dental Sciences
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- Kawano Yoshiro
- Division of Oral Anatomy, Niigata University Graduate School of Medical and Dental Sciences
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- Suzuki Akiko
- Division of Oral Anatomy, Niigata University Graduate School of Medical and Dental Sciences
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- Karaplis Andrew C.
- Endocrine Division, S.M.B.D.-Jewish General Hospital, Lady Davis Institute for Medical Research
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- Goltzman David
- Calcium Research Laboratory, Royal Victoria Hospital
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- Maeda Takeyasu
- Division of Oral Anatomy, Niigata University Graduate School of Medical and Dental Sciences Center for Transdisciplinary Research, Niigata University
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説明
Mice with a targeted deletion of parathyroid hormone (PTH)-related peptide (PTHrP) develop a form of dyschondroplasia resulting from diminished proliferation and precocious maturation of chondrocytes. The hypertrophic zone of the mutant epiphyseal cartilage revealed aberrant heterogeneous populations of chondrocytes, i.e., non-hypertrophic cells at different stages of differentiation. Therefore, PTHrP appears to play a central role in modulating cell proliferation and differentiation. The biological function of PTHrP is mediated by signaling pathway linked to the PTH/PTHrP receptor. However, the amino acids at 87-107 positions of PTHrP show a putative nucleolar targeting signal, and thought to involve in the resistance to apoptosis. Chondrocytic cell line, CFK2, transfected with truncated forms of PTHrP cDNA showed this peptide in the nucleoli mediated by translation initiating from AUG-codon and alternatively initiating from CUG codons. Thereby, PTHrP appears to act as a bipartite modulator of chondrocyte proliferation/differentiation, both through signal transduction linked to the PTH/PTHrP receptor and by its direct action in the nucleolus. Meanwhile, PTH/PTHrP receptor expression is controlled by two promoters in mouse, and the downstream promoter acts predominantly in bone and cartilage. We found 1,25-dihydroxyvitamin D3 [1,25 (OH)2D3] downregulated the activity of the downstream promoter in osteoblasts, but not in chondrocytes. This indicates that the interplay between PTH and 1,25 (OH)2D3 is specific to their overlapping roles of serum calcium regulation in bone, and not to their complementary effects on proliferation/differentiation of chondrocytes. Thus, we will review our recent examinations on cartilage development in conjunction with the biological role in PTHrP, PTH/PTHrP receptor and 1,25 (OH)2D3.
収録刊行物
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- Journal of Oral Biosciences
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Journal of Oral Biosciences 46 (2), 79-96, 2004
歯科基礎医学会
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詳細情報 詳細情報について
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- CRID
- 1390282680189880960
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- NII論文ID
- 110003166636
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- NII書誌ID
- AA11896386
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- ISSN
- 18803865
- 13490079
- http://id.crossref.org/issn/13490079
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- Crossref
- CiNii Articles
- OpenAIRE
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- 抄録ライセンスフラグ
- 使用不可