Negative Pressure Regulates BMP-9 Expression Through the MAPK/ERK5 Signaling Pathway and Thereby Promotes Fracture Healing

ORIGINAL ARTICLE
Hai Long Wang, Yuan Yuan Dou, Mu Hai Mai Ti A Bu Du Re Zha Ke, Yi Li Ya Yi Li Ha Mu, Kun Wang, Cheng Li, Qiu Cheng Chen, Yi Fei Huang, Zhan Jun Ma

 
For citation: Wang H, Dou Y, Ke M, Mu Y, Wang K, Li C, Chen Q, Huang Y, Ma Z. Negative Pressure Regulates BMP-9 Expression Through the MAPK/ERK5 Signaling Pathway and Thereby Promotes Fracture Healing. International Journal of Biomedicine. 2026;16(1):33-40. doi:10.21103/Article16(1)_OA3
 
Originally published March 5, 2026

Abstract: 

Negative pressure wound therapy (NPWT) has been widely used in wound repair and tissue regeneration, and its mechanistic role in fracture healing is gaining increasing attention. Bone morphogenetic protein-9 (BMP-9), a recognized and highly effective osteoinductive factor, plays a crucial role in bone repair. However, the regulatory mechanism of its expression under negative pressure remains unclear. This study aimed to investigate whether negative pressure wound therapy (NPWT) accelerates fracture healing by upregulating BMP-9 and osteocalcin (OCN) expression through activation of the MAPK/ERK5 signaling pathway. A tibial fracture model was established in Sprague-Dawley (SD) rats. The rats were randomly divided into the control group, the Model+Gauze group, the Model+Gauze+BIX group, the Model+NPWT group, and the Model+NPWT+BIX group. Fracture tissue was obtained 14 days after surgery for molecular and histological analysis. Real-time fluorescence quantitative PCR results showed that mRNA expression of BMP-9, OCN, MEK5, and ERK5 in the Model+NPWT group was significantly higher than that in the other groups (P < 0.05). Western blot analysis was consistent with this finding, demonstrating a significant increase in protein expression. Further immunohistochemistry revealed that OCN expression in the fracture area of the Model+NPWT group was significantly increased, suggesting a stimulatory effect on osteoblastic activity. This study demonstrates that NPWT may upregulate BMP-9 and OCN expression by activating the MAPK/ERK5 signaling pathway, thereby enhancing the osteogenic response at the fracture site and ultimately promoting fracture repair. This study provides a new perspective on the molecular mechanisms by which NPWT promotes fracture healing and provides a theoretical basis for its clinical application in fracture treatment.

Keywords: 
negative pressure • wound therapy • bone morphogenetic protein-9 • osteocalcin
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Received November 13, 2025.
Accepted January 25, 2026.
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