Crucial role of Notch signaling in osteogenic differentiation of periodontal ligament stem cells in osteoporotic rats

Abstract

Estrogen deficiency-induced osteoporosis typically occurs in postmenopausal women and has been strongly associated with periodontal diseases. Periodontal ligament stem cells (PDLSCs) isolated from the periodontal ligament can differentiate into many types of specialized cells, including osteoblast-like cells that contribute to periodontal tissue repair. The Notch signaling pathway is highly conserved and associated with self-renewal potential and cell-fate determination. Recently, several studies have focused on the relationship between Notch signaling and osteogenic differentiation. However, the precise mechanisms underlying this relationship are largely unknown. We have successfully isolated PDLSCs from both ovariectomized (OVX) and sham-operated rats. Both the mRNA and protein levels of Notch1 and Jagged1 were upregulated when PDLSCs were cultured in osteogenic induction media. Mineralization assays showed decreased calcium deposits in OVX-PDLSCs treated with a γ-secretase inhibitor compared with control cells. Thus Notch signaling is important in maintaining the osteogenic differentiation of PDLSCs in osteoporotic rats, which help in the development of a potential therapeutic strategy for periodontal disease in postmenopausal women.

Notch signaling partly regulates the osteogenic differentiation of retinoic acid-treated murine induced pluripotent stem cells

“…Correspondingly, DAPT treatment of human MSCs did not alter their alkaline phosphatase activity and mineralization relative to control cells (38). In contrast, DAPT-treated rat periodontal ligament stem cells exhibited a decrease of mineral deposition when cultured in osteogenic medium (39). Thus, the regulation of osteogenic differentiation by Notch signaling may be cell type-specific.…”

Jagged1 inhibits osteoprotegerin expression by human periodontal ligament cells

“…In addition, our group showed that immobilized Jagged1 promoted osteogenic and neurogenic differentiation in hPDLSCs, depending on the culture conditions . Jagged1 upregulation was observed during osteogenic differentiation of rat PDLs . These results imply the role of Jagged1 in the osteogenic differentiation of PDL cells.…”

Craniomaxillofacial Sources of Mesenchymal Stem Cells: A Brief Review

“…Several molecular signaling pathways are of interest in PDLSC biology, including Notch, Wnt and BMP signaling. The Notch signaling pathway is known to play a crucial role in the osteogenic differentiation of PDLSC, as determined in rat studies [35] . Notch signaling is associated with self-renewal and cell-fate determination, with both mRNA and protein expression of Notch1 and Jagged1 upregulated when PDLSC were cultured in osteogenic conditions [35] .…”

“…The Notch signaling pathway is known to play a crucial role in the osteogenic differentiation of PDLSC, as determined in rat studies [35] . Notch signaling is associated with self-renewal and cell-fate determination, with both mRNA and protein expression of Notch1 and Jagged1 upregulated when PDLSC were cultured in osteogenic conditions [35] . Inhibition of Notch signaling in PDLSC, via treatment with γ-secretase inhibitor (a protease that cleaves the Notch protein), showed decreased osteogenic differentiation [35] .…”

“…Notch signaling is associated with self-renewal and cell-fate determination, with both mRNA and protein expression of Notch1 and Jagged1 upregulated when PDLSC were cultured in osteogenic conditions [35] . Inhibition of Notch signaling in PDLSC, via treatment with γ-secretase inhibitor (a protease that cleaves the Notch protein), showed decreased osteogenic differentiation [35] . In addition, the canonical Wnt signaling pathway, which typically regulates bone homeostasis, has been shown to modulate PDLSC osteogenesis [36,37] .…”