Semaphorin 3A Inhibits Inflammation in Chondrocytes under Excessive Mechanical Stress.

Chikako Sumi,Sayuri Nishiyama,Yuki Okamoto,Makoto Yanoshita,Kotaro Tanimoto,Yuki Asakawa,Naoto Hirose,Mami Takano

doi:10.1155/2018/5703651

Chikako Sumi, Sayuri Nishiyama + Show 6 more

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https://doi.org/10.1155/2018/5703651

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Abstract

Background Excessive mechanical stress causes inflammation and destruction of cartilage and is considered one of the cause of osteoarthritis (OA). Expression of semaphorin 3A (Sema3A), which is an axon guidance molecule, has been confirmed in chondrocytes. However, there are few reports about Sema3A in chondrocytes, and the effects of Sema3A on inflammation in the cartilage are poorly understood. The aim of this study was to examine the role of Sema3A in inflammation caused by high magnitude cyclic tensile strain (CTS). Methods Expression of Sema3A and its receptors neuropilin-1 (NRP-1) and plexin-A1 (PLXA1) in ATDC5 cells was examined by Western blot analysis. ATDC5 cells were subjected to CTS of 0.5 Hz, 10% elongation with added Sema3A for 3 h. Gene expression of IL-1β, TNF-ɑ, COX-2, MMP-3, and MMP-13 was examined by qPCR analysis. Furthermore, the phosphorylation of AKT, ERK, and NF-κB was detected by Western blot analysis. Results Added Sema3A inhibited the gene expression of inflammatory cytokines upregulated by CTS in a dose-dependent manner. Addition of Sema3A suppressed the activation of AKT, ERK, and NF-κB in a dose-dependent manner. Conclusions Sema3A reduces the gene expression of inflammatory cytokines by downregulating the activation of AKT, ERK, and NF-κB pathways in ATDC5 cells under CTS.

Highlights

Mechanical stress is an important regulator of chondrocyte metabolism [1]
The expression in semaphorin 3A (Sema3A), PLXA1, and NRP-1 proteins was confirmed in cultured ATDC5 cells
To confirm changes in inflammatory mediators, Sema3A and its receptors, we examined mRNA expression levels using Quantitative Real-Time Polymerase Chain Reaction (qPCR) analysis

Summary

Introduction

Mechanical stress is an important regulator of chondrocyte metabolism [1]. Mechanical loading within the physiological range is necessary for maintaining cell homeostasis. An excessive mechanical loading over the physiological range causes abnormal inflammation through the reduction of matrix components and the synthetic imbalance between matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMPs) leads to cell destruction [4, 5]. Semaphorins are a large family of secreted and membrane-bound glycoproteins They were initially identified as regulatory molecules that define the direction of axonal growth. Expression of Sema3A and its receptors neuropilin-1 (NRP-1) and plexin-A1 (PLXA1) in ATDC5 cells was examined by Western blot analysis. Added Sema3A inhibited the gene expression of inflammatory cytokines upregulated by CTS in a dose-dependent manner. Sema3A reduces the gene expression of inflammatory cytokines by downregulating the activation of AKT, ERK, and NF-κB pathways in ATDC5 cells under CTS

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