[BMP9 promotes osteogenic differentiation of periodontal ligament stem cells under inflammatory environment via ERK5/KLF4 signaling pathway].

Purpose: To explore how bone morphogenetic protein 9(BMP9) promotes the osteogenic differentiation of periodontal ligament stem cells(PDLSCs) via ERK5/KLF4 signaling pathway under an inflammatory environment.

Methods: Recombinant adenovirus to overexpress BMP9 in PDLSCs stimulated with TNF-α was used and the expression level of osteogenic-related genes and proteins in BMP9-treated cells was examined using RT-PCR and Western blot. Then, KLF4 was overexpressed in PDLSCs via transfection and subjected to inflammatory stimulation to observe its effects on osteogenic differentiation and the expression of osteogenic-related genes. overexpression of BMP9 under the condition of KLF4 knockdown was conducted and its effects on osteogenic differentiation and the expression of osteogenic-related genes was analyzed. ERK5 inhibitor BIX02189 was used to explore the role of ERK5 in BMP9-induced osteogenic differentiation. Statistical analysis was performed with SPSS 20.0 software package.

Results: BMP9 could promote the osteogenic differentiation of PDLSCs and the expression of KLF4 in an inflammatory environment. Moreover, the overexpression of KLF4 further promoted the osteogenic differentiation of PDLSCs. However, when KLF4 was knocked down, the osteogenic differentiation promotion effect of BMP9 on PDLSCs was weakened. After BMP9 treatment, the phosphorylation level of ERK5 significantly increased. However, after adding ERK5 inhibitor, the promoting effect of BMP9 on osteogenic differentiation was significantly reduced.

Conclusions: BMP9 can promote the osteogenic differentiation of PDLSCs via ERK5/KLF4 signaling pathway in an inflammatory environment.