Icariin attenuates titanium particle‐induced inhibition of osteogenic differentiation and matrix mineralization via miR‐21‐5p

Abstract

Inhibition of bone regeneration by wear debris is the main cause of peri-prosthetic osteolysis. Here, we investigated the effect of icariin on cell proliferation, apoptosis, osteogenic differentiation and matrix mineralization of osteoblasts in an in vitro model of titanium (Ti) particle-induced osteolysis. In the present study, MC3T3-E1 cells were pretreated with 10 M icariin for 4 h and then incubated with Ti particles (0.1 mg/mL). The results showed that Ti particles inhibited cell proliferation and promoted cell apoptosis of MC3T3-E1 cells, whereas icariin pretreatment blocked the effect of Ti particles. In addition, we found that icariin stimulation alone increased ALP activity, accelerated matrix mineralization and upregulated the levels of bone morphogenetic protein 2 (BMP2), Runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and miR-21-5p; whereas, Ti particles alone exerted the opposite effects. Icariin partly reversed the effect of Ti particles on cell differentiation and mineralization. Twenty hours after transfection with antagomiR-21-5p or antagomiR-NC, the cells were pretreated with icariin for 4 h and then incubated with Ti particles. Further studies showed that partial knockdown of miR-21-5p abolished the promotion effect of icariin on osteoblast differentiation and matrix mineralization in Ti particle-stimulated MC3T3-E1 cells. In conclusion, miR-21-5p may be a potential pro-osteogenesis regulator and icariin may protect against Ti particle-induced inhibition of osteogenic differentiation and mineralization through upregulation of miR-21-5p.

MicroRNA-497-5p stimulates osteoblast differentiation through HMGA2-mediated JNK signaling pathway

“…In line with our study, miR-497-5p was downregulated in osteoarthritis cartilage, while miR-497-5p overexpression attenuated cartilage matrix degradation stimulated by IL-1β in chondrocytes [19]. ALP, which is expressed by osteoblasts, is an important marker of bone mineralization, and Alizarin Red staining is frequently applied to assess mineralization [20]. Results of the present study illustrated that osteogenesis in MC3T3-E1 cells treated with miR-497-5p mimic was more robust relative to those treated with NC mimic, as indicated by higher ALP activities and stronger formation of mineralized nodules.…”

The Effects of Biomaterial Implant Wear Debris on Osteoblasts

“…The GSK-3β/Wnt/β-catenin signaling pathway is a mediator of Ti particle-induced osteolysis in vivo. Melatonin, icariin, and ghrelin, which activate Wnt/β-catenin signaling, have been shown to rescue Ti particle-impaired cellular function in MSCs and MC3T3-E1 cells in vitro, and to attenuate particle-induced osteolysis in animal models (Wang et al, 2016;Ping et al, 2017;Lian et al, 2018;Qu et al, 2019). Furthermore, inhibiting GSK-3β activity with LiCl increased downstream β-catenin expression and mitigated Ti particle-induced suppression of osteogenesis, both in vitro and in vivo (Geng et al, 2015;Gu et al, 2017).…”

“…In addition, a potential role of the BMP signaling pathway should not be neglected Quade et al, 2020). Wang et al, 2016;Yu and He, 2016;Gu et al, 2017;Ping et al, 2017;Geng et al, 2018c;Lian et al, 2018;Qu et al, 2019 Statins (e.g., simvastatin) RhoA/ROCK Inhibitor Inflammatory reaction↓, new bone formation↑, osteoclastic bone resorption↓ von Knoch et al, 2005b;Vallés et al, 2013;Zhang et al, 2015 SB203580, triptolide Statins, a class of cholesterol-lowering drugs used clinically to reduce the risk of cardiovascular diseases, have been documented to have a beneficial effect on bone metabolism (Zhang et al, 2014). The use of statins is associated with a substantially lower risk of developing femoral osteolysis, and lower revision risk following primary total hip arthroplasty (Thillemann et al, 2010;Lübbeke et al, 2013).…”

MicroRNA-497-5p stimulates osteoblast differentiation through HMGA2-mediated JNK signaling pathway

“…In line with our study, miR-497-5p was downregulated in osteoarthritis cartilage, while miR-497-5p overexpression attenuated cartilage matrix degradation stimulated by IL-1β in chondrocytes [ 26 ]. ALP, which is expressed by osteoblasts, is an important marker of bone mineralization, and Alizarin red staining is frequently applied to assess mineralization [ 27 ]. The results of the present study illustrated that osteogenesis in MC3T3-E1 cells treated with miR-497-5p mimic was more robust relative to those treated with NC mimic, as indicated by higher ALP activities and stronger formation of mineralized nodules.…”