Tissue Eng Regen Med.
2019 Aug;16(4):405-413. 10.1007/s13770-019-00200-3.
Stimulatory Effects of KPR-A148 on Osteoblast Differentiation and Bone Regeneration
- Affiliations
-
- 1Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Institute for Hard Tissue and Bio-tooth Regeneration (IHBR), Kyungpook National University, 2177 Dalgubeol-daero, Jung-gu, Daegu 41940, Republic of Korea. epark@knu.ac.kr
- 2College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
- KMID: 2455049
- DOI: http://doi.org/10.1007/s13770-019-00200-3
Abstract
- BACKGROUND
Xanthine derivatives have been used to treat a variety of medical conditions including respiratory disease and neural degeneration. However, few studies have reported their effects on bone regeneration. Therefore, we investigated the effects of KPR-A148, a synthetic xanthine derivative on osteoblast differentiation in vitro and bone regeneration in vivo.
METHODS
The cytotoxicity of KPR-A148 was evaluated using MC3T3-E1 cells by the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltertrazolium bromide assay. The effects of KPR-A148 on osteoblast differentiation were examined by alkaline phosphatase staining, Alizarin red S staining, and real-time PCR of osteoblast differentiation marker genes. To investigate the effects of KPR-A148 on in vivo bone regeneration, a KPR-A148-containing collagen sponge was implanted into a mouse calvarial defect and KPR-A148 was injected twice, weekly. Bone regeneration was evaluated quantitatively by micro-CT and qualitatively by hematoxylin and eosin, as well as Masson's Trichrome staining.
RESULTS
KPR-A148 did not show toxicity in the MC3T3-E1 cells and promoted osteoblast differentiation in a concentration-dependent manner. 10 µM of KPR-A148 showed the most significant effect on alkaline phospatase staining and matrix mineralization. KPR-A148 increased the expression of osteoblast marker genes in both the early and late stages of differentiation. In addition, KPR-A148 significantly induced new bone formation in the calvarial defect model.
CONCLUSION
These results demonstrate that KPR-A148 strongly induces osteoblast differentiation and new bone formation. Therefore, it could be used as a potential therapeutic agent for regenerating bone following its destruction by disease or trauma.
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