The mTOR/ULK1 signaling pathway mediates the autophagy-promoting and osteogenic effects of dicalcium silicate nanopartic
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Journal of Nanobiotechnology Open Access
RESEARCH
The mTOR/ULK1 signaling pathway mediates the autophagy‑promoting and osteogenic effects of dicalcium silicate nanoparticles Wang Ruolan1,2, Chen Liangjiao3 and Shao Longquan1,2*
Abstract A novel bioactive inorganic material containing silicon, calcium and oxygen, calcium silicate ( Ca2SiO4, C2S) with a CaOSiO2 ingredient, has been identified as a potential candidate for artificial bone. Autophagy has an essential function in adult tissue homoeostasis and tumorigenesis. However, little is known about whether silicate nanoparticles ( C2S NPs) promote osteoblastic differentiation by inducing autophagy. Here we investigated the effects of C 2S NPs on bone marrow mesenchymal stem cell differentiation (BMSCs) in osteoblasts. Furthermore, we identified the osteogenic gene and protein expression in BMSCs treated with C2S NPs. We found that autophagy is important for the ability of C2S NPs to induce osteoblastic differentiation of BMSCs. Our results showed that treatment with C 2S NPs upregulated the expression of BMP2, UNX2, and OSX in BMSCs, and significantly promoted the expression of LC3 and Beclin, while P62 (an autophagy substrate) was downregulated. C2S NP treatment could also enhance Alizarin red S dye (ARS), although alkaline phosphatase (ALP) activity was not significantly changed. However, all these effects could be partially reversed by 3-MA. We then detected potential signaling pathways involved in this biological effect and found that C2S NPs could activate autophagy by suppressing mTOR and facilitating ULK1 expression. Autophagy further activated β-catenin expression and promoted osteogenic differentiation. In conclusion, C 2S NPs promote bone formation and osteogenic differentiation in BMSCs by activating autophagy. They achieve this effect by activating mTOR/ ULK1, inducing autophagy, and subsequently triggering the WNT/β-catenin pathway to boost the differentiation and biomineralization of osteoblasts. Keywords: Dicalcium silicate, Osteogenesis, Autophagy, MTOR/ULK1 Introduction Injuries, trauma, tumors, and other bone diseases are the major causes of bone defects and thus pose immense challenges for orthopedic and reconstructive surgeons. In addition, with the increase in the aging population, age-related bone loss is an urgent problem to be solved. The development of bone substitute materials provides good perspective towards bone defect management
*Correspondence: [email protected] 1 Nanfang Hospital, Southern Medical University, Guangzhou 510515, China Full list of author information is available at the end of the article
[1]. In recent years, it has been found that silicon-containing bioactive materials stimulate cell proliferation, activate the expression of osteogenic genes, and demonstrate a favorable capacity for osteogenesis both in vitro and in vivo [2]. As an important ingredient of Portland cement, dicalcium silicate (Ca2SiO4, C2S) is also an essential element in the calcium-silicate system, and it has good prospects
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