[XMU-MP-1 Enhances the Anti-Inflammatory Effects of Bone Marrow Mesenchymal Stem Cells in an Inflammatory...

To establish a bone marrow-derived inflammation model via in vitro induction and investigate the effect of XMU-MP-1 on enhancing the anti-inflammatory capacity of bone marrow mesenchymal stem cells (BMSCs) in an inflammatory microenvironment through regulating the Hippo signaling pathway.

An in vitro inflammatory model was constructed by lipopolysaccharide (LPS) induction. BMSCs were randomly divided into three groups: control group, LPS group, and XMU-MP-1 intervention group. The inflammatory response of BMSCs was evaluated by detecting the expression levels of inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Alcian blue staining, alizarin red staining, and analysis of the expression of osteogenic and chondrogenic marker genes were performed to assess the differentiation potential of BMSCs. Meanwhile, the expression changes of Hippo pathway-related proteins were detected to explore the underlying mechanism.

Compared with the control group, LPS stimulation significantly increased the secretion levels of IL-6 and TNF-α in BMSCs by 13.7 times and 7.08 times, respectively (both P<0.001), and reduced the number of osteogenic calcium nodules by 55.31% and the positive staining level of chondrogenic cartilage matrix by 30.67% (both P<0.01), which significantly inhibited its osteogenic and chondrogenic differentiation abilities. After intervention with 100 nmol/L XMU-MP-1, the expression levels of IL-6 and TNF-α in BMSCs were decreased by 41.24% and 63.84% compared with the LPS group (both P<0.01), while the 80 nmol/L intervention group decreased by 43.06% and 65.7% (both P<0.01). The number of osteogenic calcium nodules in the 80 and 100 nmol/L XMU-MP-1 intervention groups increased by 54.42% and 98.01% compared with the LPS group, and the positive staining level of chondrogenic cartilage matrix increased by 11.41% and 21.14% (all P<0.01), and the osteogenic and chondrogenic related indicators were significantly restored. Mechanistic studies showed that XMU-MP-1 could downregulate the phosphorylation level of key upstream proteins in the Hippo pathway, accompanied by increased YAP activity.

XMU-MP-1 can improve the anti-inflammatory capacity and differentiation function of BMSCs in an inflammatory microenvironment to a certain extent, and its effect may be related to the regulation of the Hippo-YAP signaling pathway. This study provides experimental evidence for further exploring the regulatory mechanism of the bone marrow microenvironment under inflammatory conditions.