摘要
Bone morphogenetic protein 9 (BMP9) has remarkable potential to induce the differentiation of mesenchymal stem cells (MSCs) towards the osteoblastic lineage. Additionally,research suggests that certain growth factors have the ability to potentiate BMP9-inducedosteogenic differentiation of MSCs. Sonic Hedgehog (Shh) plays an indispensable role in theregulation of skeletal development. The objective of this research was to assess the potentialinfluence of Shh on BMP9-induced osteogenic differentiation of MSCs. Our findings indicatedthat Shh effectively enhanced BMP9-induced early and late osteogenic differentiation of MSCs,and increased BMP9-induced expression/transcriptional activity of osteogenesis-related transcription factors. Besides, it was observed that Shh promoted BMP9-induced ectopic bone formation of MSCs in vivo. Moreover, BMP9 was able to facilitate the repair of bone defects inrats, while Shh further accelerated this reparative process. Mechanistically, Shh enhancedthe activation of the Smad1/5/8 signaling pathway which was induced by BMP9. Furthermore,GANT-61, an inhibitor of Gli1 and Gli2, attenuated the enhancing effect of Shh on BMP9-induced osteogenic differentiation of MSCs. Collectively, the co-administration of BMP9 andShh may present a promising therapeutic approach for the treatment of fracture nonunion, delayed fracture healing, and bone defects.
基金
supported by the Chongqing Young and Middle-aged Medical High-end Talent Project(China)(No.2019GDRC001)
Chongqing Talent Innovation and Entrepreneurship Leader Project(China)(No.cstc2022ycjhbgzxm0103)
the funding from Deyang Science and Technology Foundation(Sichuan,China)(No.2021SZZ060)
the Program for Youth Innovation in Future Medicine of Chongqing Medical University(No.W0086).
