title: Lentivirus-induced knockdown of LRP1 induces osteoarthritic-like effects and increases susceptibility to apoptosis in chondrocytes via the nuclear factor-κB pathway.
abstract: Low-density lipoprotein receptor-related protein 1 (LRP1) is known to regulate cell survival and inflammation. The present study investigated the involvement of LRP1 in the regulation of tumor necrosis factor (TNF)-α-induced expression of matrix metalloproteinase (MMP)-13. Furthermore, the study aimed to elucidate the mechanisms underlying the effects of LRP1 on TNF-α-induced inflammation and apoptosis of chondrocytes. Lentivirus-mediated RNA interference techniques were used to knockdown the LRP1 gene. Subsequently, the effects of LRP1 on TNF-α-induced MMP-13 expression were determined using quantitative polymerase chain reaction, western blot analysis and ELISA. Furthermore, the TNF-α-induced intracellular pathway was investigated using a nuclear factor (NF)-κB inhibitor (Bay 11-7082). In addition, the effect of LRP1 regulation on growth and apoptosis in chondrocytes was investigated using western blot analysis and a TUNEL assay. LRP1 knockdown was shown to increase TNF-α-induced MMP-13 expression via the activation of the NF-κB (p65) pathway, which reduced the expression of collagen type II and cell viability. In addition, LRP1 inhibited cell apoptosis by increasing the expression of phospho-Akt and B-cell lymphoma 2 (Bcl-2), while suppressing the expression of caspase-3 and Bcl-2-associated X protein. The results of the present study indicated that LRP1 was able to inhibit TNF-α-induced apoptosis and inflammation in chondrocytes. Therefore, LRP1 may be an effective osteoarthritis inhibitor, potentially providing a novel approach for antiarthritic therapeutics.
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Erping
authors.initials: E
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Huifeng
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Yinyuan
authors.initials: Y
authors.lastname: Ding
keywords: apoptosis; low-density lipoprotein receptor-related protein-1; matrix metalloproteinase-13; osteoarthritis; tumor necrosis factor-α