Early Supplemental ?2-Macroglobulin Attenuates Cartilage And Bone Damage By Inhibiting Inflammation In Collagen ? Induced Arthritis Model

Objective:(1).Does supplemental intra-articular A2 M have a chondroprotective effect and preserve the joint function in CIA mouse model?(2).Does higher dose of A2 M have stronger inhibition against degrading enzymes?(3).Does FMT a sensitive bioimaging to monitor inflammation dynamically?Methods:Sixty 8-week-old mice(DBA/1)were randomized into 4 groups(n =15/ group):1)CIA + 1.2?g of A2M;2)CIA + 0.8?g of A2M;3)CIA + 0.4?g of A2M;4)Vehicle + PBS.Intra-articular injection of A2 M was made into the right ankle and an equal amount of PBS was injected into the left ankle as internal control at day 36,43 and 50.The clinical score and ankle thickness were recorded from day 21 and on every other following day until the event of sacrifice.The change of inflammation was monitored by FMT in vivo.Bone damage was examined by X-ray at day 35(no bone change)and 57.The inflammation,cartilage and bone damage were analyzed by histology and immunohistochemistry.The cartilage and inflammation related gene expression was quantified by Real-time PCR.Results:100% mice showed ankle inflammation at day 33.Lower clinical score and ankle thickness was found in the mice treated by A2 M compared with PBS-treated mice after day 43.The SHM score in A2M-treated mice was lower than that in the PBS-treated mice.FMT data indicated that the inflammation markers MMPSense and ProSense were much higher in the PBS-treated ankles than in the contralateral sides treated with A2 M.Histology and X-ray analysis indicated that A2 M administration showed lower level of inflammation infiltration and synovial hyperplasia,while demonstrating typical cartilage and bone organization with more COL II and Aggrecan staining compared to PBS treated ankles.In addition,RT-PCR showed that MMP-3,-9,-13,COL X and Runx2 were significantly lower in A2 M treatment groups than that in PBS treated animals.Conclusion:Early supplemental intra-articular A2 M exerts anti-inflammatory effect and attenuate cartilage and bone damage.And the higher dose of A2 M have stronger inhibition against degrading enzymes.In addition,FMT can be a sensitive bioimaging to monitorinflammation dynamically.