Lentivirus-induced knockdown of low density lipoprotein receptor-related protein 1 aggravates cartilage damage in a rat model of osteoarthritis / 中国组织工程研究

ABSTRACT

BACKGROUND:Emerging evidence demonstrates that low density lipoprotein receptor-related protein 1 (LRP1)isinvolved in lipid metabolism and regulation of inflammatory reaction. OBJECTIVE:To explore the effectof lentivirus-induced knockdown of low density lipoprotein receptor-related protein 1 on cartilage damage and matrix metaloproteinase 13 in a rat model of osteoarthritis, so as to assess the role of low density lipoprotein receptor-related protein 1 in the pathogenesis of osteoarthritis. METHODS:Sixty-fourSprague-Dawleyratswere included andramdomlydivided into four groups (n=16 for each) negative control group, no surgery; sham-surgery group, onlythearticular cavity of the knee was exposed; osteoarthritisplus shLRP1 group, rat osteoarthritis models were established by cutting anterior cruciate ligament and removing the medial meniscus partly folowed by an intra-articular injection of lentivirus-mediated siRNA at 2 days after surgery, once a week for 2 consecutive weeks; osteoarthritis group,an intra-articular injection of the negative control lentivirus was performed after surgery. Rats inthe four groups started running on theself-made electric treadmil from 5 days after modeling, 30 minutes per day,totaly 500 meters. Cartilage damage and matrix metaloproteinase 13 expression in cartilage tissues were determined at 2, 4, 6 weeks after surgery. RESULTS AND CONCLUSION:Gross and pathological observations showed that lentivirus-induced knockdown of lowdensity lipoprotein receptor-related protein 1 aggravatedcartilage damage intherat model of osteoarthritis. At 6 weeks after surgery, Mankin’s scoreand matrix metaloproteinase 13 expression inthecartilage tissues in osteoarthritis plus shLRP1 groupweresignificantly increased compared with other three groups (P< 0.05). These findings indicate that a simulation model of osteoarthritis is developed by cutting anterior cruciate ligament and removing the medial meniscus partly combined with running onthe treadmil. Lentivirus-induced knockdown ofLRP1aggravates cartilage damage in a rat model of osteoarthritis