Bovine lactoferrin improves bone mass and microstructure in ovariectomized rats via OPG/RANKL/RANK pathway.
OBJECTIVE
Lactoferrin (LF), an 80-kDa iron-binding glycoprotein, is a pleiotropic factor found in colostrum, milk, saliva and epithelial cells of the exocrine glands. The aim of this study was to evaluate the effects of LF on the bones in ovariectomized (Ovx) rats and to identify the pathways that mediate the anabolic action of LF on the bones.


METHODS
Female Sprague-Dawley rats (6-month-old) underwent ovariectomy, and were treated with different doses of LF (10, 100, 1000, and 2000 mg·kg(-1)·d(-1), po) or with 7β-estradiol (0.1 mg·kg(-1), im, each week) as the positive control. By the end of 6 month-treatments, the bone mass and microstructure in the rats were scanned by micro-computed tomography (micro-CT), and the bone metabolism was evaluated with specific markers, and the mRNA levels of osteoprotegerin (OPG) and the receptor-activator of nuclear factor κB ligand (RANKL) in femur were measured using qRT-PCR.


RESULTS
LF treatment dose-dependently elevated the bone volume (BV/TV), trabecular thickness (TbTh) and trabecular number (TbN), and reduced the trabecular separation (TbSp) in Ovx rats. Furthermore, higher doses of LF (1000 and 2000 mg·kg(-1)·d(-1)) significantly increased the bone mineral density (BMD) compared with the untreated Ovx rats. The higher doses of LF also significantly increased the serum levels of OC and BALP, and decreased the serum levels of β-CTx and NTX. LF treatment significantly increased the OPG mRNA levels, and suppressed the RANKL mRNA levels, and the RANKL/OPG mRNA ratio in Ovx rats.


CONCLUSIONS
Oral administration of LF preserves the bone mass and improves the bone microarchitecture. LF enhances bone formation, reduces bone resorption, and decreases bone mass loss, possibly through the regulation of OPG/RANKL/RANK pathway.
Provincial Clinical Medical College of Fujian Medical University, Fuzhou, China. hjm996@yahoo.com.cn
Jian-Ming
JM
Hou
Ying
Y
Xue
Qing-Ming
QM
Lin
D000704:Analysis of Variance; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007781:Lactoferrin / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D009929:Organ Size; D010024:Osteoporosis / Q000473:pathology / Q000517:prevention & control; D053244:Osteoprotegerin / Q000378:metabolism*; D010052:Ovariectomy; D053245:RANK Ligand / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*; D055114:X-Ray Microtomography
D050071:Bone Density Conservation Agents; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C506032:Tnfrsf11b protein, rat; D007781:Lactoferrin