Inhibition of osteoporosis in autoimmune disease prone MRL/Mpj-Fas(lpr) mice by N-3 fatty acids.
OBJECTIVE
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease involving the breakdown of cartilage and juxta-articular bone, which is often accompanied by decreased bone mineral density (BMD) and increased risk of fracture. Anti-inflammatory omega-3 fatty acids may prevent arthritis and bone loss in MRL/lpr mice model of arthritis and in humans.


METHODS
In this study, the effect of long term feeding of 10% dietary n-3 (fish oil (FO)) and n-6 (corn oil (CO)) fatty acids begun at 6 weeks of age on bone mineral density (BMD) in different bone regions in an MRL/lpr female mouse model of RA was measured at 6, 9, and 12 months of age by dual energy x-ray absorptiometry (DEXA). After sacrificing the mice at 12 months of age, antioxidant enzyme activities were measured in spleen, mRNA for receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) was measured by RT-PCR in lymph nodes, and synovitis was measured in leg joints.


RESULTS
At 6, 9 and 12 months of age, BMD was significantly higher (p < 0.05) in distal femur, proximal tibia, and lumbar spine of FO fed mice than those of CO fed mice. Spleen catalase (CAT) and superoxide dismutase (SOD) activities were also significantly higher (p < 0.01) in FO fed mice than in CO fed mice. Histology of knee joints revealed mild synovitis in CO fed mice, which was not present in FO fed mice. RT-PCR analysis of lymph nodes revealed decreased RANKL mRNA (p < 0.001) expression and enhanced OPG mRNA expression (p < 0.01) in FO fed mice compared to CO fed mice.


CONCLUSIONS
These results suggest beneficial effects of long-term FO feeding in maintaining higher BMD and lower synovitis in this mouse model. These beneficial effects may be due, in part, to increased activity of antioxidant enzymes, decreased expression of RANKL, and increased expression of OPG in FO fed mice thereby altering the RANKL/OPG ratio. These significant beneficial effects on BMD suggest that FO may serve as an effective dietary supplement to prevent BMD loss in patients with RA.
Bhattacharya
Arunabh
A
Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Rahman
Mizanur
M
Banu
Jameela
J
Lawrence
Richard A
RA
McGuff
Howard S
HS
Garrett
I R
IR
Fischbach
Michael
M
Fernandes
Gabriel
G
D015502:Absorptiometry, Photon / Q000379:methods; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000150:complications*; D001327:Autoimmune Diseases / Q000150:complications*; D015519:Bone Density / Q000187:drug effects*; D002352:Carrier Proteins / Q000187:drug effects; D002374:Catalase / Q000187:drug effects; D003314:Corn Oil / Q000008:administration & dosage; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage; D005260:Female; D005395:Fish Oils / Q000627:therapeutic use; D006023:Glycoproteins / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000187:drug effects; D051379:Mice; D019463:Mice, Inbred MRL lpr; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control*; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger / Q000187:drug effects; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013482:Superoxide Dismutase / Q000187:drug effects; D013585:Synovitis / Q000517:prevention & control; D013997:Time Factors
D002352:Carrier Proteins; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005395:Fish Oils; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D003314:Corn Oil; D002374:Catalase; D013482:Superoxide Dismutase