@Article{biocell.2025.072716,
AUTHOR = {Yong Huang, Xiandeng Li, Qingling Jing, Qin Zhang, Chungui Huang},
TITLE = {BMP-2 Inhibits the Inflammatory Response and Promotes Bone Formation in Rats with Femoral Fracture by Activating the AMPK Signaling Pathway},
JOURNAL = {BIOCELL},
VOLUME = {49},
YEAR = {2025},
NUMBER = {11},
PAGES = {2195--2216},
URL = {http://www.techscience.com/biocell/v49n11/64549},
ISSN = {1667-5746},
ABSTRACT = { <b>Objective:</b> Mesenchymal stem cells (MSCs) are important cells in bone tissue engineering. Bone morphogenetic protein-2 (BMP-2) effectively treats bone defects and nonunion. The purpose of this study is to investigate whether BMP-2 promotes bone formation and femoral fracture healing by inhibiting inflammation and promoting osteogenic differentiation of MSCs, in order to provide an experimental basis for developing more efficient fracture treatment strategies. <b>Methods:</b> Bone marrow-derived MSCs (BMSCs) were isolated from rats and treated with OE-BMP-2, the 5<sup>′</sup>-adenosine monophosphate-activated protein kinase (AMPK) signal agonist 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), and the inhibitor Compound C. Osteogenic differentiation was evaluated through an alkaline phosphatase (ALP) kit, Western blot, and Alizarin Red S (ARS) staining. A rat model of femoral fracture was constructed, and fracture healing in the rats was detected by X-ray, microcomputed tomography (CT), and pathological staining. The AMPK signaling pathway and inflammation levels in the BMSCs and fracture model rats were measured by Western blot and enzyme-linked immunosorbent assay (ELISA) kits. <b>Results:</b> After BMP-2 overexpression, the ALP activity in osteogenic BMSCs was significantly increased (increased to 253.64%), the levels of osteogenic differentiation proteins (Osterix and osteocalcin) and p-AMPK Thr172 protein were significantly increased, and the concentrations of inflammatory factors were decreased. In rat fracture tissues, BMP-2 overexpression promoted the expression of p-AMPK Thr172 protein and bone callus formation, increased bone volume (increased to 22.22%), reduced the number of fibrous components in the cartilage matrix, increased the numbers of osteoblasts and chondrocytes, increased the expression of osteogenic differentiation proteins, and reduced the content of inflammatory factors in the serum. After AICAR intervention, ALP activity and the expression of osteogenic differentiation proteins in BMSCs and fracture tissues further increased, and the level of inflammation decreased. However, the changes in osteogenic differentiation and inflammation levels were significantly reversed after Compound C intervention. <b>Conclusion:</b> BMP-2 activated the AMPK signaling pathway, inhibited the inflammatory response, and effectively promoted the osteogenic differentiation of BMSCs and femoral fracture healing in rats.},
DOI = {10.32604/biocell.2025.072716}
}