Effects Of Curcumin On Bone Mineral Density And Osteoprotegerin And Receptor Activator Of Nuclear Factor-κB Ligand Protein Expression In Rats With Adjuvant Arthritis

OBJECTIVE： Rheumatoid arthritis (RA) is characterised by the presence ofdestruction of joint cartilage and bone, which usually occur in early period of diseaseand throughout the complete course of disease, and is irreversible. If no active treatment,bone destruction in RA patients will soon happen, so early prevention of bonedestruction is an important way to treatment of RA patients. In recent years, The role ofcurcumin play in rheumatoid arthritis has been pay more and more attention. In thisexperiment, we establish adjuvant arthritis (AA) model to simulate the pathogenesis ofRA, and observe the effect of curcumin on bone mineral density, expression ofosteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL),to explore the role of curcumin for the treatment of RA and mechanism of boneprotection.METHODS:40male SD were randomly divided into normal group(n=10), modelgroup(n=10), curcumin group(n=10), methotrexat group (n=10) by random digits table.Adaptive feeding for1week, arthritis was induced by an intradermal injection of0.1mL complete Freund’s adjuvant in the foot pad of right hind limb of rats, the day ofmodeling recorded as d0. On d7after modeling began with intraperitoneal injection, therats of curcumin group were treated with curcumin50mg kg-1d-1intraperitonealinjection which dissolved in10%dimethyl sulfoxide continuously for21days, and ratsof methotrexat group were treated with methotrexat0.5mg kg-1d-1by intraperitonealinjection for7times, rats of model group was given10%DMSO5ml kg-1d-1for21days, all rats from normal group were allowed to drink water freely. To compare thegeneral situation change of all rats, and calculate body mass growth rate according tobody mass growth in rats. The effects of treatment were monitored by measurement ofarthritis index number(AI) at d7, d14, d21, d28, and evaluated inflammation of arthritisrats. On d28after modeling, all rats were killed. All synovial membrane were sent forroutine histological evaluation with HE staining, pathological grading were made according to inflammatory cell infiltration, degree of synovial cell proliferation andconnective tissue fibrosis. Bone density, which was in region of interest of the wholeright tibia and distal tibial, were detected by Dual-energy X-ray. RANKL and OPGprotein expression were measured by the method of ELISA and Western Blotting. Dataentry and statistical analysis were performed using SPSS17.0software.RESULTS: Impact of curcumin on the general situation in rats (including general state,growth rate of body mass and arthritis index): Rats in mdel group were poor mentalstate, poor eating habits, movement disorder, dull hair, the general state of rats incurcumin group were better than that in model group, but less than that in normal group.Body mass growth of rats from curcumin group and methotrexate group weresignificantly faster than that in model group. Compared with model group, degree ofinflammation in curcumin group at d14, d21, d28were statistically different from that inmethotrexate group, however, the differences were not statistically significant betweencurcumin group and methotrexate group. Impact of CUR on histopathology (includingsynovial pathology and bone density) of adjuvant arthritis rats: Curcumin couldinfluence synovium pathology change of adjuvant arthritis rats, the pathological pictureshowed that infiltration of joint synovial cell, proliferation of synovial fibroblasts inmodel group rats were significantly increased, compared with normal group. Pathologyof rats synovial tissue in rats of curcumin group and methotrexate group weresignificantly improved, compared with that in rats of model group. There was nosignificant difference about overall bone density among four groups of rats, while bonemineral density of interest areas in rats of curcumin group was significantly higher thanthat in rats of model group. The impact of curcumin on expression of proteins inadjuvant arthritis rats (including RANKL, OPG protein in serum, synovial tissue):Expression of RANKL, OPG protein in serum and synovial tissue of curcumin group,based on pairwise comparison between with model group, the results were statisticallysignificant. serum and synovial RANKL/OPG ratio were significantly lower than in the model group; with MTX group had no significant difference in the results. Comparedwith model group, expression of RANKL, OPG protein in serum, synovial tissue werestatistically significant, RANKL/OPG ratio in serum or synovial tissue was significantlylower than that in model group, there was no significant difference in results when thesecompared with methotrexate group.CONCLUSIONS: Curcumin can improve general state, moderate degree of synovitisand improve synovial pathology damage of adjuvant arthritis rats, increase bone densityand inhibit bone loss. So curcumin may exert a protective effect on arthritis rats byregulating OPG/RANKL signaling pathway.