文献类型：期刊文献

英文题名：Boric Acid Inhibits RANKL-Stimulated Osteoclastogenesis In Vitro and Attenuates LPS-Induced Bone Loss In Vivo

作者：Xu, Bingbing[1];Dong, Fanhe[1];Yang, Pei[1];Wang, Zihan[1];Yan, Ming[2];Fang, Jian[1];Zhang, Yun[1]

机构：[1]Shaoxing Univ, Coll Med, Huancheng West Rd 508, Shaoxing 312000, Peoples R China;[2]Hangzhou Dianzi Univ, Sch Automat, Xiasha Higher Educ Zone, 1158 2nd Ave, Hangzhou 310018, Peoples R China

年份：0

外文期刊名：BIOLOGICAL TRACE ELEMENT RESEARCH

收录：SCI-EXPANDED(收录号：WOS:000782162900003)、、Scopus(收录号：2-s2.0-85127666208)、WOS

基金：This work was supported by Natural Science Foundation of Zhejiang Province (LY21H060001), Zhejiang Public Welfare Technology Application Research Project (LGF18H060006), and National Undergraduate Innovation and Entrepreneurship Training Program (202110349006).

语种：英文

外文关键词：Boric acid; RANKL; Osteoclastogenesis; PERK-eIF2 alpha pathway; LPS; Bone loss

外文摘要：Boron and boric acid (BA) can promote osteogenic differentiation and reduce bone resorption, which controls bone growth and maintenance of bone tissue. It has been reported that BA activates PERK-eIF2 alpha signaling to induce cytoplasmic stress granules and cell senescence in human prostate DU-145 cells. However, whether BA can affect osteoclasts formation and LPS-induced inflammatory bone loss, and the role of the PERK-eIF2 alpha pathway in the process, remains unknown. In vitro, RAW264.7 cells were pre-treated with boric acid (BA, 1, 10, 100 mu mol/L) for 4 h, and then incubated with receptor activator of nuclear factor-kappaB ligand (RANKL, 50 ng/mL) in the presence or absence of BA for 5 days. CCK-8 and tartrate-resistant acid phosphatase (TRAP) were used to examine cell viability, osteoclastogenesis, and bone resorption; quantitative real-time PCR was performed to examine mRNA levels of c-Fos, nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), TRAP, and cathepsin K; western blotting was used to examine protein expressions of glucose-regulated protein 78 (GRP78), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), eukaryotic initiation factor 2 alpha (eIF2 alpha), and phosphorylated eIF2 alpha (p-eIF2 alpha). In vivo, lipopolysaccharide (LPS)-induced bone loss model in mice was established, and micro-computed tomography (micro-CT) scanning, bone biochemical analysis, and osteoclastogenic cytokines were detected to evaluate the effect of BA on LPS-induced bone loss. In our vitro results showed that BA treatment for 5 days inhibited osteoclasts formation as well as osteoclastic bone resorption in a dose-dependent manner. The expression of osteoclasts marker genes c-Fos, NFATc1, TRAP, and cathepsin K were attenuated by BA. Immunoblotting analysis demonstrated that BA attenuated RANKL-induced PERK-eIF2 alpha pathway activation. The in vivo data indicated that BA significantly prevented lipopolysaccharide (LPS)-induced bone loss. Our findings strongly suggest that BA may be a promising agent for the treatment of bone destructive diseases caused by excessive osteoclastogenesis.