Development of Novel Therapy for Achondroplasia: Use of Parathyroid Hormone

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Achondroplasia (ACHs) and thanatophoric dysplasia (TD) are representative diseases of micromelic short stature that are elicited by a constitutively activated FGFR3 caused by point-mutation in the receptor molecule. Based on the mutated point in the receptor, there are several types of diseases of which the severity varies. In the chondrogenic cell line (ATDC5), the signaling cascade in the fibroblast growth factor 3 (FGFR3) was silenced by a overexpression of the mutated FGFR3 that resulted in decreased expression of the mRNA of the parathyroid hormone-related peptide (PTHrP); and also apoptosis was induced. The expression levels of PTHrP were inversely correlated with the severity of the disease; and the replacement of PTHrP prevented the apoptotic changes in the cell lines. In the following studies, however, we selected rhPTH that possesses a high homology and had been clinically used in the treatment of osteoporosis. In the organ culture, rhPTH remarkably elongated the proximal and distal cartilages of the ACH transgenic mice (ACHtg) and expressed collagen X similarly to the wild mice. An <i>in vivo</i> study of rhPTH significantly increased the growth of the long bones of ACHtg in comparison with those of the control (saline). The future prospects of parathyroid hormone (PTH) therapy of ACH are to be discussed.<br>


  • Clinical Pediatric Endocrinology

    Clinical Pediatric Endocrinology 14(Supplement23), S23_39-S23_44, 2005

    The Japanese Society for Pediatric Endocrinology


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