Bone morphogenetic protein-6 and parathyroid hormone-related protein coordinately regulate the hypertrophic conversion in mouse clonal chondrogenic EC cells, ATDC5.
We evaluated the roles of bone morphogenetic protein (BMP)-6, BMP-4 and parathyroid hormone-related protein (PTHrP) in the hypertrophic conversion using mouse chondrogenic EC cells, ATDC5. In ATDC5 cells, the expression of BMP-6 and PTHrP receptor mRNAs increased in parallel with the progression of chondrogenic differentiation of these cells, exhibiting a time course similar to that of type II collagen, a phenotypic marker of proliferating chondrocytes, while BMP-4 mRNA was continuously expressed throughout the differentiation processes. The expression of type X collagen mRNA, a phenotypic marker of hypertrophic chondrocytes, was upregulated by BMP-6 and BMP-4, and downregulated by PTHrP(1-141). The expression of BMP-6 mRNA was upregulated while that of BMP-4 mRNA was downregulated by both BMP-6 and BMP-4. Moreover, the expression of BMP-6 mRNA was downregulated by PTHrP(1-141). Furthermore, even in the presence of PTHrP(1-141), BMP-6 increased the transcript level of type X collagen in a dose-dependent manner. These results indicate that transiently expressed BMP-6 promotes the hypertrophic conversion in association with the augmentation of BMP-6 gene expression by BMP signals and that both BMP-6 and PTHrP coordinately regulate the rate of the hypertrophic conversion of ATDC5 cells.
Ito
H
H
Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan.
Akiyama
H
H
Shigeno
C
C
Nakamura
T
T
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation; D003094:Collagen / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation; D051379:Mice; D010281:Parathyroid Hormone / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
C525810:Bmp4 protein, mouse; C525817:Bmp6 protein, mouse; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D012333:RNA, Messenger; C066078:parathyroid hormone-related protein (1-141); D003094:Collagen