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KMID : 1007020040020020080
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Korean Soceity of Osteroporosis
2004 Volume.2 No. 2 p.80 ~ p.90
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The Effects of Recombinant Human Parathyroid Hormone[rhPTH(1-84)] on Bone Changes Induced by the Different Glucocorticoids in Mice
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Choi Sung-Hee
Rhee Yu-Mie
Li Song-Zhe
Shin Chan-Soo
Jang Hak-Chul
Lim Sung-Kil
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Abstract
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Objectives: In recently, there is growing evidence that there is also non- genomic activity of glucocorticoids, via cytosolic receptor or via non-specific physicochemical activity. We tried to find whether there was difference of genomic and non-genomic action in changes of mouse bones. We also tried to find the impact of human parathyroid hormone on changes of bone induced by steroids with different mechanisms.
Methods: We used 7∼8 weeks old male ICR mouse with maximal bone density. Dexamethasone and betamethasone was used because they have the same genomic action but have a 6-fold difference for non-genomic action. The bone density was measured by QDR 4500A(Hologic, Waltham, MA, USA). Animals were divided into 5 groups as; group 1: control, group 2: dexamethasone only, group 3: betamethasone only, group 4: dexamethasone and rhPTH(1-84), group 5: betamethasone and rhPTH(1-84) for 32 days.
Results: In group 2, although the average weight was increased, the bone mineral density was decreased significantly, compared to other groups. The bone density reduction was not significant in group 3. Such reduction of the bone density tended to be improved with human parathyroid hormone applied, particularly in group 4. In group 2, there was a marked reduction in the number of ALP positive colony while no change in CFU-Fs colony. The number of the ALP positive colony increased significantly in group 4. Histomorphometrical study demonstrated that the volume and thickness of the trabecular bone decreased in group 2 and increased in group 4 and 5.
Conclusion: Reduction of bone mineral density after dexamethasone treatment might be due to inhibition of differentiation from mesenchymal cell into osteoblast lineage, based on both the numbers of ALP positive colonies for early osteoblast and mineralization. We suggested that the accumulation of the non-genomic action of glucocorticoids has a significant impact on bone in vivo. Human parathyroid hormone injection has successfully inhibited the loss of bone density by dexamethasone.
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KEYWORD
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Steroid, Non-genomic action, Osteoporosis, rhPTH, Osteoblast
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