Direct conversion of fibroblasts to osteoblasts as a novel strategy for bone regeneration in elderly individuals

Abstract

Mortality caused by age-related bone fractures or osteoporosis is steadily increasing worldwide as the population ages. The pace of the development of bone regeneration engineering to treat bone fractures has consequently increased in recent years. A range of techniques for bone regeneration, such as immunotherapy, allografts, and hydrogel therapy, have been devised. Cell-based therapies using bone marrow-derived mesenchymal stem cells and induced pluripotent stem cells derived from somatic cells are considered to be suitable approaches for bone repair. However, these cell-based therapies suffer from a number of limitations in terms of efficiency and safety. Somatic cells can also be directly differentiated into osteoblasts by several transcription factors. As osteoblasts play a central role in the process of bone formation, the direct reprogramming of fibroblasts into osteoblasts may hence be a new way to treat bone fractures in elderly individuals. Here, we review recent developments regarding the therapeutic potential of the direct reprogramming of cells for bone regeneration.

Fig. 1. Bone remodeling.

Bone formation and resorption are mainly regulated by the interplay between osteoblast differentiation and osteoclast activation. With increasing age, the balance shifts to more bone resorption than bone formation

Fig. 2. Timeline for the development of osteogenic cells.

The upper panel shows the development of iPSC-derived osteogenic cells, whereas the lower panel shows the development of direct conversion-derived osteogenic cells