A gene expression profile for the lower osteogenic potent of bone-derived MSCs from osteoporosis with T2DM and the potential mechanism

Abstract

Background Osteoporosis (OP) patients complicated with type II diabetes mellitus (T2DM) has a higher fracture risk than the non-diabetic patients, and mesenchymal stem cells (MSCs) from T2DM patients also show a weaker osteogenic potent. The present study aimed to provide a gene expression profile in MSCs from diabetic OP and investigated the potential mechanism. Methods The bone-derived MSC (BMSC) was isolated from OP patients complicated with or without T2DM (CON-BMSC, T2DM-BMSC). Osteogenic differentiation was evaluated by qPCR analysis of the expression levels of osteogenic markers, ALP activity and mineralization level. The differentially expressed genes (DEGs) in T2DM-BMSC was identified by RNA-sequence, and the biological roles of DEGs was annotated by bioinformatics analyses. The role of silencing the transcription factor (TF), Forkhead box Q1 (FOXQ1), on the osteogenic differentiation of BMSC was also investigated. Results T2DM-BMSC showed a significantly reduced osteogenic potent compare to the CON-BMSC. A total of 448 DEGs was screened in T2DM-BMSC, and bioinformatics analyses showed that many TFs and the target genes were enriched in various OP- and diabetes-related biological processes and pathways. FOXQ1 had the highest verified fold change (abs) among the top 8 TFs, and silence of FOXQ1 inhibited the osteogenic differentiation of CON-BMSC. Conclusions Our study provided a comprehensive gene expression profile of BMSC in diabetic OP, and found that downregulated FOXQ1 was responsible for the reduced osteogenic potent of T2DM-BSMC. This is of great importance for the special mechanism researches and the treatment of diabetic OP.

Short- and long-term exposure to high glucose induces unique transcriptional changes in osteoblasts in vitro

“…Long-term BMSC cultures in high glucose have been shown to exhibit decreased differentiation capability without indication of senescence ( Al-Qarakhli et al, 2019 ). Xia et al (2022) studied BMSCs from osteoporotic patients with or without T2DM using RNA-seq and noticed that T2DM-derived BMSCs exhibit decreased differentiation and mineralization capacity, which they attributed to attenuated expression of Forkhead Box Q1 (FOXQ1). However, we did not observe changes in FOXQ1 in our dataset.…”

FOXQ1 inhibits the progression of osteoarthritis by regulating pyroptosis

“…As a nucleic acid binding protein, FOXQ1 can inhibit the replicative senescence by decreasing the levels of IL-6 and IL-8 via modulation of the SIRT1-NFκB pathway [ 39 ], and the FOXQ1-ANXA2 complex can promote the Wnt/β-catenin pathway in bone MSCs, thereby leading the osteogenic differentiation subsequently [ 40 ]. In addition, Xia et al have found that silencing of FOXQ1 significantly inhibits the osteogenic differentiation of bone-derived MSCs from osteoporosis with T2DM [ 25 ]. Based on the previous study results, FOXQ1 could be seen as a chondrocyte biogenesis factor in osteogenesis, but the role of FOXQ1 in cartilage degradation of OA is still unclear.…”

Multiple pretreatments can effectively improve the functionality of mesenchymal stem cells

“…MSCs are widely employed in traumatic tissue repair, immune disorders, and cancer therapy. The proliferative capacity and immunogenicity of MSCs from different human populations vary greatly, and the osteogenic potential of MSCs derived from diabetic patients is decreased than health volunteers[ 18 ], while MSCs isolated from patients with autoimmune diseases have morphological and some functional abnormalities[ 19 ], which implies that the normal MSCs transplants may restore the MSCs function and alleviate the disease.…”