Red Yeast Rice Increases Bone Morphogenetic Protein-2 Expression and Enhances Fracture Healing Process in Delayed Union Models of Sprague-Dawley Rats: A Preclinical Study

Abstract

Aryadi Kurniawan,1 Felais Hediyanto Pradana,1 Evelina Kodrat,2 Anissa Feby Canintika,1 Aufa Kunti Riona Aryandhani3 1Department of Orthopedics and Traumatology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 2Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 3Radboud University, Nijmegen, NetherlandCorrespondence: Aryadi Kurniawan, Department of Orthopedics and Traumatology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia, Email [email protected]: Delayed union management is both challenging and expensive. Statins, which are HMG-CoA reductase inhibitors, induce bone morphogenetic protein-2 (BMP-2) gene expression, which in turn increases bone formation. Red yeast rice contains monacolin, which has a similar activity to lovastatin as an HMG-CoA reductase inhibitor. Red-yeast rice is readily available and inexpensive. This study aimed to demonstrate the effectiveness of red yeast rice in enhancing fracture healing in a delayed union model through increased expression of BMP-2.Materials and Methods: This experimental animal study was conducted using 24 delayed union Sprague-Dawley (SD) rats divided into four groups (n=6 each), consisting of; the 4-weeks-given-red yeast rice extract group (4RYR), 2-weeks-given-red yeast rice extract group (2RYR), 4-weeks-control group (4C), and 2-weeks-control group (2C). The animals were euthanized in the second and fourth week. Immunohistochemical staining was used to assess BMP-2 expression using an Immunoreactive Score (IRS). The fracture healing process was evaluated using histomorphometry by measuring the fibrous area, cartilage area, and woven bone area percentage.Results: In the 2RYR group, there was significantly higher BMP-2 expression (p=0.03), less fibrous area (p=0.05), and larger cartilage area (p= 0.04) than in the 2C group. In the 4RYR group, there was significantly higher expression of BMP-2 (p=0.011), larger woven bone area (p=0.01), and less fibrous area (p = 0.03) than in the 4C group. There was also a significantly smaller fibrous area (p=0.02), a larger cartilage area (p=0.05), and a larger woven bone area (p=0.04) in the 4RYR group than in the 2RYR group. The BMP-2 expression in the 2RYR group was as high as that in the 4RYR group.Conclusion: Red yeast rice effectively improved fracture healing by increasing BMP-2 expression in a delayed-union model in SD rats.Keywords: delayed union model, BMP-2 expression, red yeast rice, fracture healing

Keywords

• delayed union model
• bmp-2 expression
• red yeast rice
• fracture healing