Published online Oct 26, 2013. doi: 10.4252/wjsc.v5.i4.136
Revised: August 30, 2013
Accepted: September 14, 2013
Published online: October 26, 2013
Bone is a dynamic tissue that is constantly renewed by the coordinated action of two cell types, i.e., the bone-resorbing osteoclasts and the bone-forming osteoblasts. However, in some circumstances, bone regeneration exceeds bone self repair capacities. This is notably often the case after bone fractures, osteolytic bone tumor surgery, or osteonecrosis. In this regard, bone tissue engineering with autologous or allogenic mesenchymal stem cells (MSCs) is been widely developed. MSCs can be isolated from bone marrow or other tissues such as adipose tissue or umbilical cord, and can be implanted in bone defects with or without prior amplification and stimulation. However, the outcome of most pre-clinical studies remains relatively disappointing. A better understanding of the successive steps and molecular mechanisms involved in MSC-osteoblastic differentiation appears to be crucial to optimize MSC-bone therapy. In this review, we first present the important growth factors that stimulate osteoblastogenesis. Then we review the main transcription factors that modulate osteoblast differentiation, and the microRNAs (miRs) that inhibit their expression. Finally, we also discuss articles dealing with the use of these factors and miRs in the development of new bone MSC therapy strategies. We particularly focus on the studies using human MSCs, since significant differences exist between osteoblast differentiation mechanisms in humans and mice for instance.
Core tip: Several excellent reviews on the transcription factors involved in osteoblast differentiation have recently been published, but none also presented the microRNAs (miRs) that control the expression of these transcription factors. Moreover, most of these reviews mainly reported mouse studies but important differences are well acknowledged between humans and mice. For instance vitamin D3, an important hormone controlling bone homeostasis, has very different effect in these species. Therefore, in the present review we particularly focus on human cells to present the transcription factors and miRs controlling mesenchymal stem cells-osteoblastic differentiation.