Organic Nitrate Maintains Bone Marrow Blood Perfusion in Ovariectomized Female Rats: A Dynamic, Contrast-Enhanced Magnetic Resonance Imaging (MRI) Study

Pharmaceutics

Yi-Xiang J. Wang¹  Chun Hay Ko²  James F. Griffith¹  Min Deng¹  Hing Lok Wong³  Tao Gu¹ 

[1] Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China; E-mails:;Institute of Chinese Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, China; E-Mail:;Jockey Club Centre for Osteoporosis Care and Control, School of Public Health and Primary Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China; E-mail:

关键词: nitrates;    osteoporosis;    DCE MRI;    bone mineral density;    osteoblast;    osteoclast;   

DOI  :  10.3390/pharmaceutics5010023

来源: mdpi

【 摘 要 】

This study investigated the effects of nitrate on bone mineral density (BMD) and bone marrow perfusion in ovariectomized (OVX) female rats, and also the effects of nitrate on in vitro osteoblastic activity and osteoclastic differentiation of murine monocyte/macrophage RAW 264.7 cells. Female Sprague–Dawley rats were divided into OVX + nitrate group (isosorbide-5-mononitrate, ISM, 150 mg/kg/ day b.i.d), OVX + vehicle group, and control group. Lumbar spine CT bone densitometry and perfusion MRI were performed on the rats at baseline and week 8 post-OVX. The OVX rats’ BMD decreased by 22.5% ± 5.7% at week 8 (p < 0.001); while the OVX + ISM rats’ BMD decreased by 13.1% ± 2.7% (p < 0.001). The BMD loss difference between the two groups of rats was significant (p = 0.018). The OVX rats’ lumbar vertebral perfusion MRI maximum enhancement (Emax) decreased by 10.3% ± 5.0% at week 8 (p < 0.005), while in OVX + ISM rats, the Emax increased by 5.5% ± 6.9% (p > 0.05). The proliferation of osteoblast-like UMR-106 cells increased significantly with ISM treatment at 0.78 µM to 50 μM. Treatment of UMR-106 cells with ISM also stimulated the BrdU uptake. After the RAW 264.7 cells were co-treated with osteoclastogenesis inducer RANKL and 6.25 μM ~ 100 μM of ISM for 3 days, a trend of dose-dependent increase of osteoclast number was noted.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.