Angiogenesis inhibitor attenuates parathyroid hormone-induced anabolic effect.
In vivo osteogenic responses to anabolic stimuli are expected to be accompanied by angiogenesis as well as in the process of remodeling of bone. Consequently, angiogenesis might play an important role in mediating bone forming stimulating effect of parathyroid hormone (PTH). To investigate this relationship, we used actively growing young Sprague-Dawley rats and CKD-732, one of the angiogenesis inhibitor (AI) to reveal the relationship of angiogenesis in the effect of PTH. The groups were divided as (1) vehicle [VEH group], (2) PTH(1-84) [PTH group], (3) AI alone [AI group], (4) PTH(1-84)+AI concomitance [PTH-AI group] and were treated for 6 weeks. The bone mineral density (BMD) of PTH group was higher than VEH group and the gain of bone mass was attenuated in PTH-AI group. The maximal failure load in PTH group was higher than VEH group, but it was definitely attenuated by concurrent use of AI. Moreover, the toughness showed similar significant deterioration in PTH-AI group. General bone turnover was also significantly decreased in PTH-AI group as shown by the absence of increase in osteocalcin and beta-crosslaps and by decrease in metaphyseal length. The BMD or the biomechanic data of AI only group were similar to the VEH group, suggesting the minimal effect of AI itself on the normal modeling phase of the growing rats. In conclusion, the angiogenesis seemed to contribute to completing the anabolic effect of PTH especially for bone strength.
Rhee
Yumie
Y
Department of Internal Medicine College of Medicine, Yonsei University, 134 Shinchon-Dong, Seodaemun-Gu, Seoul, Republic of Korea.
Park
So Young
SY
Kim
Yoo Mee
YM
Lee
Sihoon
S
Lim
Sung-Kil
SK
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight; D015519:Bone Density; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002934:Cinnamates / Q000494:pharmacology*; D003510:Cyclohexanes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology*; D005260:Female; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D002934:Cinnamates; D003510:Cyclohexanes; D004852:Epoxy Compounds; D010281:Parathyroid Hormone; D012717:Sesquiterpenes; C487952:CKD732