- 作者: Hyuck Choi, Byung-Chul Jeong, Min-Suk Kook and Jeong-Tae Koh
- 作者服務機構: 1. Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea 2. Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea
- 中文摘要: --
- 英文摘要:
Background
Healing of bone defects is a dynamic and orchestrated process that relies on multiple growth factors and cell types. Bone morphogenetic protein 2 (BMP2) is a key growth factor for bone healing, which stimulates mesenchymal stem cells to differentiate into osteoblasts. Betulinic acid (BetA) is a natural pentacyclic triterpenoid from plants. This study aimed to examine combinatory effects of BetA and BMP2 on ectopic bone generation in mice.
Results
In MC3T3-E1 preosteoblast culture, 10–15 μM of BetA increased the alkaline phosphatase (ALP) activity and expression levels of osteogenic marker genes without the decreased cell viability. In addition, BetA synergistically enhanced BMP2-induced gene expressions and mineralization with the enhancement of phosphorylation of Smad1/5/8 and p38. In an in vivo ectopic bone formation model, combination of BetA (50 μg) and BMP2 (3 μg) resulted in increases in the amount of new bone generation, compared with treatment with BMP2 alone. Histological studies showed that bone generation with cortical and trabecular structures was resulted from the combination of BetA and BMP2.
Conclusion
BetA can enhance in vivo osteogenic potentials of BMP2, possibly via stimulating Smad 1/5/8 and p38 pathways, and combination of both agents can be considered as a therapeutic strategy for bone diseases. - 中文關鍵字: --
- 英文關鍵字: Betulinic acid, BMP2, Bone formation, Mineralization, Smad1/5/8, p38