Action mechanisms of progesterone in managing bone loss in periodontitis: An in vitro study

Progesterone (PG) is a sex steroid hormone that has the potential to control bone loss in periodontitis. This study aimed to reveal the underlying mechanisms of action of PG on osteogenesis in periodontitis and to identify key target genes in vitro.

Primary human periodontal mesenchymal stem cells (hPDLSCs) were isolated and treated with lipopolysaccharide (LPS) in combination with or without PG. Subsequently, RNA sequencing was performed after osteogenic induction, and the differential expressed genes (DEGs), functional enrichment (GO and KEGG), and protein-protein interaction (PPI) were bioinformatically analysed. The expression of two key DEGs, BUB1 and UBE2C, were verified by qRT-PCR. Relevant regulatory mechanisms involving osteogenesis were verified by detecting the levels of osteogenesis-related proteins, Runx2 and ALP (Western blot) after silencing.

A total of 212 DEGs (104 up-regulated and 108 down-regulated genes) were identified between the LPS and LPS + PG groups. These DEGs were mainly enriched in the GO terms of cell division, adhesion, sodium/potassium channel, etc., and in the KEGG terms of oocyte meiosis, estrogen signalling, cell apoptosis, and adhesion. In the PPI networks, most of the hub proteins are related to cell cycle and division. Of note, BUB1 and UBE2C, two node genes, were down-regulated in LPS-treated hPDLSCs. The intervention of PG significantly eliminated the effects of LPS on the down-regulation of BUB1 and UBE2C. Upon LPS treatment, silencing of BUB1 and UBE2C both reversed the PG-induced osteogenesis in hPDLSCs.

BUB1 and UBE2C, two important mediators of osteogenesis, are potential molecular targets of PG. PG may promote the osteogenesis of hPDLSCs under inflammatory conditions through the up-regulation of BUB1 and UBE2C, suggesting a potential mechanism that may contribute to the remission of periodontitis.