Osteogenic Potential of Tauroursodeoxycholic Acid as an Alternative to rhBMP-2 in a Mouse Spinal Fusion Model

Abstract

The non-union rate after lumbar spinal fusion is potentially as high as 48%. To support efficient bone regeneration, recombinant human bone morphogenetic protein-2 (rhBMP-2) is commonly used as it is regarded as the most potent bone-inducing molecule. However, recently, there have been increasing concerns on the use of rhBMP-2 such as serious complications, including seroma and heterotopic ossification, and the low quality of bone at the center of fusion mass. Thus, many studies were conducted to find and to develop a potential alternative to rhBMP-2. In this study, we investigated the osteogenic potential of tauroursodeoxycholic acid (TUDCA) in the mouse fusion model and compared its effects with rhBMP-2. Twenty-four mice underwent bilateral posterolateral lumbar spinal fusion bone formation at L4-L5. Collagen sponge infused with saline, TUDCA, or rhBMP-2 was implanted at the fusion area. Two and 4 weeks postimplantation, bone formation and tissue regeneration were evaluated via micro-computed tomography and histological analysis. Compared with the TUDCA-treated group, the rhBMP-2 treatment produced a higher amount of bone fusion formation after 2 weeks but also showed higher resorption of the centralized bone after 4 weeks. Interestingly, the TUDCA-treated group developed higher trabecular thickness compared with rhBMP-2 after 4 weeks. Moreover, TUDCA treatment showed distinct angiogenic activity in human umbilical vein endothelial cells as confirmed by an in vitro tube formation assay. Our findings suggest that TUDCA is comparable to rhBMP-2 in supporting bone regeneration and spinal bone formation fusion by increasing trabecular thickness and promoting angiogenesis. Finally, our results indicate that TUDCA can be utilized as a potential alternative to rhBMP-2.