Analysis of short-term treatment with the phosphodiesterase type 5 inhibitor tadalafil on long bone development in young rats
| Autor: | Haoruo Jia, Luqiang Wang, Robert J. Tower, Ling Qin, Michael A. Levine |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism Long bone Regulator 030204 cardiovascular system & hematology Weight Gain Bone and Bones Tadalafil Rats Sprague-Dawley 03 medical and health sciences Chondrocytes 0302 clinical medicine Physiology (medical) Internal medicine Cortical Bone medicine Animals RNA Messenger Cyclic GMP Endochondral ossification Cyclic Nucleotide Phosphodiesterases Type 5 Bone Development Chemistry Phosphodiesterase Natriuretic Peptide C-Type X-Ray Microtomography Phosphodiesterase 5 Inhibitors Endochondral bone growth Rats 030104 developmental biology medicine.anatomical_structure Endocrinology Animals Newborn cGMP-specific phosphodiesterase type 5 Cancellous Bone Epiphyses Intracellular Research Article medicine.drug |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 315:E446-E453 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | Cyclic GMP (cGMP) is an important intracellular regulator of endochondral bone growth and skeletal remodeling. Tadalafil, an inhibitor of the phosphodiesterase (PDE) type 5 (PDE5) that specifically hydrolyzes cGMP, is increasingly used to treat children with pulmonary arterial hypertension (PAH), but the effect of tadalafil on bone growth and strength has not been previously investigated. In this study, we first analyzed the expression of transcripts encoding PDEs in primary cultures of chondrocytes from newborn rat epiphyses. We detected robust expression of PDE5 as the major phosphodiesterase hydrolyzing cGMP. Time-course experiments showed that C-type natriuretic peptide increased intracellular levels of cGMP in primary chondrocytes with a peak at 2 min, and in the presence of tadalafil the peak level of intracellular cGMP was 37% greater ( P < 0.01) and the decline was significantly attenuated. Next, we treated 1-mo-old Sprague Dawley rats with vehicle or tadalafil for 3 wk. Although 10 mg·kg−1·day−1 tadalafil led to a significant 52% ( P < 0.01) increase in tissue levels of cGMP and a 9% reduction ( P < 0.01) in bodyweight gain, it did not alter long bone length, cortical or trabecular bone properties, and histological features. In conclusion, our results indicate that PDE5 is highly expressed in growth plate chondrocytes, and short-term tadalafil treatment of growing rats at doses comparable to those used in children with PAH has neither obvious beneficial effect on long bone growth nor any observable adverse effect on growth plate structure and trabecular and cortical bone structure. |
| Databáze: | OpenAIRE |
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