Semaphorin 3A Inhibits Inflammation in Chondrocytes under Excessive Mechanical Stress

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.

Protective effects of cilengitide on inflammation in chondrocytes under excessive mechanical stress

“…Scale bars = 50 µm. (Su et al, 2014;Sumi et al, 2018;Yanoshita et al, 2018). In this study, high-magnitude cyclic tensile stress was applied on ATDC5 chondrocytes in a condition of 10% cell elongation for 24 h, which caused the upregulated expression of inflammatory cytokines and matrixdegrading enzymes (Figure 2).…”

“…We have been investigating the relationship between excessive mechanical stress and chondrogenic destruction. The cyclic tensile stress is associated with expression of many kinds of inflammatory cytokines and proteinase in chondrocytes (Su et al, ; Sumi et al, ; Yanoshita et al, ). In this study, high‐magnitude cyclic tensile stress was applied on ATDC5 chondrocytes in a condition of 10% cell elongation for 24 h, which caused the upregulated expression of inflammatory cytokines and matrix‐degrading enzymes (Figure ).…”

“…It has previously been reported that the application of a 3% strain (0.17 Hz and 2 h) on chondrocytes resulted in weak or no biological response, whereas loading between 3 and 10% strain (0.17–0.5 Hz and 2–12 h) led to anabolic responses (Bleuel et al, ). We have conducted in vitro study applying the mechanical strain on this condition (10% elongation, 0.5 Hz, and 3 h), which is considered as excessive stress for chondrocytes (Sumi et al, ; Yanoshita et al, ). The cells were harvested 1, 3, 6, 12, and 24 h after the application of excessive mechanical stress and were frozen at −80°C until used for real‐time reverse‐transcription polymerase chain reaction (RT‐PCR) and western blot analysis.…”

Protective effect of ethyl acetate fraction from Semen sojae germinatum, the processed sprout of Chinese black soybean, on rat experimental osteoarthritis

“…At present, it has been clinically recognized that functional dietary food or food products could be used as proper health supplements or phyto-pharmaceuticals to fight against multiple disease conditions [17,18]. In particular, the benefits of soy-derived products on OA have been clearly established [14][15][16][17][18][19]. For example, the insufficient consumption of soy products is considered as a predictor for knee OA among elderly Japanese women [19], while soy intake improved the biochemical markers and the symptoms of OA [20].…”

“…The inflammatory responses in the synovial membrane further damage the surrounding joint tissues through the release of pro-inflammatory cytokines into the synovial fluid [13]. IL-1β and TNF-ɑ are two important potent inflammatory cytokines contributing to the induction of joint inflammation, cartilage catabolism, even chondrocyte death in OA [14][15][16]. We found that the urea-adjusted synovial lavage concentrations of IL-1β and TNF-ɑ were significantly enhanced in ACLT OA group, compared to the sham-operated controls (P < 0.01).…”