N,N-Dimethylformamide inhibits high glucose-induced osteoporosis via attenuating MAPK and NF-κB signalling

Bone & Joint Research

article

Ya Dong Liu¹  Jian Feng Liu²  Bin Liu² 

[1] Department of Spine Surgery, The First Hospital of Jilin University;Department of Hand Surgery, The First Hospital of Jilin University

关键词: DMF;    Osteoporosis;    Diabetes;    osteoclasts;    macrophages;    nuclear factor kappa B;    Western blot;    bone marrow;    Diabetes mellitus;    Tartrate-resistant acid phosphatase;    ovariectomy;    micro-CT;   

DOI  :  10.1302/2046-3758.114.BJR-2020-0308.R2

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

AimsThe role of N,N-dimethylformamide (DMF) in diabetes-induced osteoporosis (DM-OS) progression remains unclear. Here, we aimed to explore the effect of DMF on DM-OS development.MethodsDiabetic models of mice, RAW 264.7 cells, and bone marrow macrophages (BMMs) were established by streptozotocin stimulation, high glucose treatment, and receptor activator of nuclear factor-κB ligand (RANKL) treatment, respectively. The effects of DMF on DM-OS development in these models were examined by micro-CT analysis, haematoxylin and eosin (H&E) staining, osteoclast differentiation of RAW 264.7 cells and BMMs, H&E and tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA) of TRAP5b and c-terminal telopeptides of type 1 (CTX1) analyses, reactive oxygen species (ROS) analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), Cell Counting Kit-8 (CCK-8) assay, and Western blot.ResultsThe established diabetic mice were more sensitive to ovariectomy (OVX)-induced osteoporosis, and DMF treatment inhibited the sensitivity. OVX-treated diabetic mice exhibited higher TRAP5b and c-terminal telopeptides of type 1 (CTX1) levels, and DMF treatment inhibited the enhancement. DMF reduced RAW 264.7 cell viability. Glucose treatment enhanced the levels of TRAP5b, cathepsin K, Atp6v0d2, and H+-ATPase, ROS, while DMF reversed this phenotype. The glucose-increased protein levels were inhibited by DMF in cells treated with RANKL. The expression levels of antioxidant enzymes Gclc, Gclm, Ho-1, and Nqo1 were upregulated by DMF. DMF attenuated high glucose-caused osteoclast differentiation by targeting mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signalling in BMMs.ConclusionDMF inhibits high glucose-induced osteoporosis by targeting MAPK and NF-κB signalling.

【 授权许可】

CC BY-NC