Pinoresinol diglucoside alleviates ovariectomy-induced osteoporosis by modulating the "Microbiota-gut-bone" axis

Pinoresinol diglucoside (PDG) is one of the main constituents of Eucommiae cortex. PDG has a known therapeutic effect on postmenopausal osteoporosis (PMOP). However, the regulatory mechanisms of this effect need to be further investigated.

We verified the osteogenic-differentiation effect of PDG on bone marrow mesenchymal stem cells (BMSCs). Then, we used bilateral ovariectomized (OVX) mice as a model animal for PMOP. Micro-computed tomography imaging was used to detect changes in femur bone mineral density. Histopathology was performed to observe the bone microstructure of the femur and pathological changes of the colonic mucosa. Enzyme-linked immunosorbent assay was used to detect the changes in the serum bone-conversion factor and the expression levels of inflammatory factors in the colon. Immunofluorescence detection elucidated the expression levels of colonic tight junction proteins. We additionally performed 16S rDNA high-throughput sequencing to analyze the genes of bacterial flora and gas chromatography-mass spectrometry to detect the expression levels of short-chain fatty acids (SCFAs) in the feces.

Our analysis suggests PDG promotes high expression of osteogenic genes in BMSCs and may alleviate osteoporosis. Additionally, PDG increases the expression levels of colonic tight junction proteins, alleviates colonic inflammation, enhances the intestinal SCFA content, and promotes greater abundance of dominant genera such as g_Akkermansia and g_Parabacteroides while reducing that of g_Ruminococcus opportunistic pathogens.

PDG can promote osteogenic differentiation of BMSCs and increase bone mineral density. Its mechanism of action is closely related to regulation of the "microbiota-gut-bone" axis.