Lentivirus-induced knockdown of LRP1 induces osteoarthritic-like effects and increases susceptibility to apoptosis in chondrocytes via the nuclear factor-κB pathway

Yang,Erping; Zheng,Huifeng; Peng,Hao; Ding,Yinyuan

doi:10.3892/etm.2015.2471

Lentivirus-induced knockdown of LRP1 induces osteoarthritic-like effects and increases susceptibility to apoptosis in chondrocytes via the nuclear factor-κB pathway

Authors:
- Erping Yang
- Huifeng Zheng
- Hao Peng
- Yinyuan Ding
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Affiliations: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Published online on: May 5, 2015 https://doi.org/10.3892/etm.2015.2471
Pages: 97-105
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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