Journal
EXPERIMENTAL AND THERAPEUTIC MEDICINE
Volume 10, Issue 1, Pages 97-105Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/etm.2015.2471
Keywords
tumor necrosis factor-alpha; matrix metalloproteinase-13; low-density lipoprotein receptor-related protein-1; apoptosis; osteoarthritis
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Funding
- National Natural Science Foundation of China [61308110]
- Wuhan University College of Medicine
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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)--induced expression of matrix metalloproteinase (MMP)-13. Furthermore, the study aimed to elucidate the mechanisms underlying the effects of LRP1 on TNF--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--induced MMP-13 expression were determined using quantitative polymerase chain reaction, western blot analysis and ELISA. Furthermore, the TNF--induced intracellular pathway was investigated using a nuclear factor (NF)-B 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--induced MMP-13 expression via the activation of the NF-B (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--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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