LIM mineralization protein‑1 inhibits IL‑1β‑induced human chondrocytes injury by altering the NF‑κB and MAPK/JNK pathways

Ou,Dijun; Liu,Sheng; Tong,Changjun; Tan,Hezhong; Yang,Yadong; He,Chunlei

doi:10.3892/etm.2021.10983

LIM mineralization protein‑1 inhibits IL‑1β‑induced human chondrocytes injury by altering the NF‑κB and MAPK/JNK pathways

Authors:
- Dijun Ou
- Sheng Liu
- Changjun Tong
- Hezhong Tan
- Yadong Yang
- Chunlei He
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Affiliations: Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong 518000, P.R. China, Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China
Published online on: November 21, 2021 https://doi.org/10.3892/etm.2021.10983
Article Number: 61
Copyright: © Ou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteoarthritis (OA) is a common degenerative disease that is associated with the degradation of articular cartilage. Accumulating evidence has confirmed that LIM mineralization protein‑1 (LMP‑1) is an important agent of bone formation and has been shown to be osteoinductive in various types of disease. However, the underlying mechanisms of LMP‑1 in the pathogenesis of OA remain unknown. The present study aimed to evaluate the role and potential mechanism of LMP‑1 in IL‑1β‑stimulated OA chondrocytes. CHON‑001 cells were transfected with pcDNA3.1‑LMP‑1, pcDNA3.1, negative control‑small interfering (si)RNA or LMP‑1 siRNA for 24 h and then induced by IL‑1β for 12 h to establish an OA model in vitro. Cell viability, apoptosis and inflammatory cytokine (IL‑6, IL‑8 and TNF‑α) release were assessed using MTT assay, ﬂow cytometry and ELISA, respectively. The expression levels of LMP‑1, cleaved‑caspase 3, phosphorylated (p)‑p65, p65, p‑JNK and JNK were analyzed using reverse transcription‑quantitative PCR and western blotting. Overexpression of LMP‑1 notably alleviated the IL‑1β‑induced inflammatory response in CHON‑001 cells, as shown by increased cell viability, decreased apoptosis, suppressed expression of cleaved‑caspase 3 and a decreased cleaved‑caspase 3/caspase 3 ratio. Moreover, IL‑1β‑induced secretion of IL‑6, IL‑8 and TNF‑α in CHON‑001 cells; this was reversed by pcDNA3.1‑LMP‑1. However, knocking down LMP‑1 expression exert opposite effects on the IL‑1β‑induced inflammatory response in CHON‑001 cells, as evidenced by the decreased cell viability, increased apoptosis, enhanced expression of cleaved‑caspase 3 and cleaved‑caspase 3/caspase 3 ratio and enhanced secretion of IL‑6, IL‑8 and TNF‑α observed. The present data demonstrated that LMP‑1 siRNA notably inhibited LMP‑1 expression, suppressed cell viability, promoted apoptosis and enhanced cleaved‑caspase 3 expression and cleaved‑caspase 3/caspase 3 ratio. In addition, LMP‑1 siRNA promoted the release of inflammatory factors in CHON‑001 cells. It was also found that pcDNA3.1‑LMP‑1 inhibited p‑p65 and p‑JNK expression, as well as decreasing the p‑p65/p65 and p‑JNK/JNK ratio. Nevertheless, there was no significant difference in the mRNA expression levels of p65 and JNK between the groups. Taken together, these findings indicated that overexpression of LMP‑1 alleviated IL‑1β‑induced chondrocytes injury by regulating the NF‑κB and MAPK/JNK pathways, suggesting that LMP‑1 may be a valuable therapeutic agent for OA treatment.

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