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

Abstract

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.

Dysfunctional Microcirculation of the Lumbar Vertebral Marrow Prior to the Bone Loss and Intervertebral Discal Degeneration

“…These results demonstrated that alterations in microcirculation of the lumbar vertebral marrow had an influence on its BMD and intervertebral discal healthy status. Some studies had been conducted with an aim to prevent and cure osteoporosis 18 and discal degenerative disease 19 through maintaining the microcirculation perfusion to the bone marrow with drugs or cell therapy. These successful experimental therapeutics also supported our hypothesis that microcirculation perfusion dysfunction of the vertebral marrow is a cause leading to bone mass loss and intervertebral disc degeneration.…”

Decrease with aging of the microcirculatory function of the lumbar vertebral marrow preceding the loss of bone material density and the onset of intervertebral discal degeneration: A study about the potential cause

“…These results demonstrated that alterations in microcirculation of the lumbar vertebral marrow had an influence on its BMD and the health of the intervertebral disc. Some studies had been done with drugs or cell therapy aimed at prevention and cure of osteoporosis 18 and DDD 19 through maintaining the microcirculatory perfusion to the bone marrow. These successful experimental therapeutics also supported our hypothesis that dysfunction of the microcirculatory perfusion of the vertebral marrow is a cause leading to loss of bone mass and intervertebral disc degeneration.…”

Evaluation of a Topical Herbal Agent for the Promotion of Bone Healing

“…(iii) Osteoblast Proliferation and Viability Assays . The osteoblast proliferation and viability were measured using 5-bromo-2′-deoxyuridine (BrdU) [ 24 ] incorporation and MTT cell viability assay [ 19 , 25 ], respectively. Briefly, UMR-106 cells were seeded in DMEM with 10% v/v FBS.…”