Alpinetin promotes fracture healing in rats with osteoporotic fracture by regulating the cAMP/PKA/CREB signaling pathway
- VernacularTitle:山姜素调节cAMP/PKA/CREB信号通路促进骨质疏松性骨折大鼠骨折愈合
- Author:
Fei LU
1
;
Jing ZHOU
;
Tao JIN
Author Information
- Publication Type:Journal Article
- Keywords: alpinetin; cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate-responsive element binding protein; osteoporosis; fracture healing; rat
- From: Chinese Journal of Tissue Engineering Research 2025;29(12):2438-2443
- CountryChina
- Language:Chinese
- Abstract: BACKGROUND:Alpinetin has anti-inflammatory,antitumor and antibacterial effects and has been proven to alleviate osteoporosis,but the effect and mechanism of alpinetin on osteoporotic fractures are still unclear.OBJECTIVE:To investigate the improvement effect of alpinetin in rates with osteoporotic fracture by regulating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP-responsive element binding protein (CREB) signaling pathway.METHODS:A rat model of osteoporotic fracture was constructed using bilateral ovariectomy. The successfully modeled rats were randomly separated into model group,low-,medium-,and high-dose alpinetin group,and inhibitor group,with 12 rats per group. Another 12 rats were regarded as the sham operation group. On the day of fracture,rats in the low-,medium-,and high-dose alpinetin groups were gavaged with 7.5,15,and 30 mg/kg alpinetin+intraperitoneally injected with an equal amount of normal saline,respectively;the inhibitor group was gavaged with 30 mg/kg alpinetin+intraperitoneally injected with 5 mg/kg H-89 (a pathway inhibitor);and the model and sham operation groups were given (gavaged+intraperitoneally injected) an equal amount of normal saline,once a day for 8 consecutive weeks. Radiological examination was applied to evaluate fracture healing and assess healing scores;bone mineral density scanners were used to measure bone mineral density at the fracture site;three-point bending experiment and compression experiment were conducted to evaluate the biomechanical status of the femur;pathological damage at the fracture site in rats was observed by hematoxylin-eosin staining;enzyme linked immunosorbent assay (ELISA) was used to detect changes in serum alkaline phosphatase,osteocalcin,type Ⅰ collagen cross-linked C-terminal peptide,and cAMP levels;western blot was applied to detect the expression of bone morphogenetic protein 2 and cAMP/PKA/CREB pathway proteins in femoral tissue.RESULTS AND CONCLUSION:Compared with the sham operation group,the fracture healing score,bone mineral density,maximum load,maximum stress,alkaline phosphatase,osteocalcin,cAMP levels,bone morphogenetic protein 2,p-PKA/PKA,p-CREB/CREB expression in the model group were decreased,the level of type Ⅰ collagen cross-linked C-terminal peptide was increased (P<0.05). The above indicators showed opposite changes in all the alpinetin groups compared with the model group (P<0.05). Compared with the high-dose alpinetin group,the changes in the above indicators were reversed in the inhibitor group (P<0.05). To conclude,alpinetin may accelerate fracture healing in osteoporotic fracture rats,by activating the cAMP/PKA/CREB signaling pathway.
