The Role and Mechanism of miRNA-1224 in the Polygonatum sibiricum Polysaccharide Regulation of Bone Marrow-Derived Macrophages to Osteoclast Differentiation

Rejuvenation Res. 2019 Oct;22(5):420-430. doi: 10.1089/rej.2018.2126. Epub 2019 Mar 15.

Abstract

MicroRNAs (miRNAs) are endogenous noncoding small molecule RNAs that regulate cell proliferation, differentiation, fat metabolism, and hormone secretion. Studies have shown that miRNAs regulate the processes related to osteoporosis, including the differentiation of osteoblasts, osteoclasts, and chondrocytes, and are one of the important regulatory factors of some bone metabolic diseases. In our previous study, it has been revealed that natural compound Polygonatum sibiricum polysaccharide (PSP) can promote osteoblast formation and block osteoclastogenesis through Wnt/β-catenin signaling pathway. This study was designed to investigate whether PSP can inhibit expression of osteoclast-related genes by Hippo signaling pathway, which was prevented by effectively blocking the expression of miR-1224. This study showed that there were 27 differentially expressed miRNAs when PSP inhibits osteoclastogenesis, the most notable of which was miR-1224. Furthermore, the study showed that PSP increased the level of Limd1, which was the target gene of miR-1224. In conclusion, these findings demonstrate that PSP suppressed osteoclastogenesis in vitro through the Hippo signaling pathway based on miR-1224. This study may aid in the development of a therapeutic approach utilizing PSP for the enhancement of bone health and prevention of osteoporosis.

Keywords: Hippo signaling pathway; Polygonatum sibiricum polysaccharide; miR-1224.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Gene Expression / drug effects
  • Hippo Signaling Pathway
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Osteoclasts / cytology
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism*
  • Osteogenesis / drug effects
  • Osteogenesis / genetics
  • Plants, Medicinal
  • Polygonatum*
  • Polysaccharides / pharmacology*
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • Limd1 protein, mouse
  • MIRN1224 microRNA, mouse
  • MicroRNAs
  • Polysaccharides
  • Protein Serine-Threonine Kinases