Evaluation of Human Dental Pulp Stem Cells Expressing BMP2/7 Heterodimers in a Doxycycline-Inducible Manner

对以强力霉素诱导方式表达BMP2/7异二聚体的人类牙髓干细胞进行评价

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作者:Edit Hrubi,Ferenc Tóth,Gergely Nagy,József Tőzsér,Csaba Hegedűs

Abstract

The BMP2/7 heterodimer is known as a stronger inducer of osteogenic differentiation than BMP2 or BMP7 homodimers. Our aim was to establish BMP2/7-expressing human dental pulp stem cells (DPSCs) to evaluate tReceived: 23 October 2025; Revised: 29 November 2025; Accepted: 3 December 2025; Published: 3 December 2025 he osteogenic potential of the genetically modified cells. Lentiviral transduction was used to introduce the Tet-ON-regulated transgene-containing vector to the cells. Endogenous heterodimers were detected at the mRNA and protein levels using RNA-seq, qPCR, and Western blot, while secreted heterodimers were detected using ELISA assays. Osteogenic differentiation was monitored by measuring alkaline phosphatase (ALP) activity, mineralization, and the expression levels of RUNX2 and ALPL genes. Our results showed that ALP activity did not change in the transduced DPSCs; however, increased mineralization was detected, which correlates with the results obtained by RNA sequencing. Based on our results, BMP2/7-expressing DPSCs could be used in the treatment of bone defects, where heterodimers may have not only autocrine but also paracrine effects.

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