Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and Application in Osteoporosis Treatment

Abstract

Osteoporosis is a progressive skeletal disease characterized by decreased bone mass and degraded bone microstructure, which leads to increased bone fragility and risks of bone fracture. Osteoporosis is generally age related and has become a major disease of the world. Uncovering the molecular mechanisms underlying osteoporosis and developing effective prevention and therapy methods has great significance for human health. Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into osteoblasts, adipocytes, or chondrocytes, and have become the favorite source of cell-based therapy. Evidence shows that during osteoporosis, a shift of the cell differentiation of MSCs to adipocytes rather than osteoblasts partly contributes to osteoporosis. Thus, uncovering the molecular mechanisms of the osteoblast or adipocyte differentiation of MSCs will provide more understanding of MSCs and perhaps new methods of osteoporosis treatment. The MSCs have been applied to both preclinical and clinical studies in osteoporosis treatment. Here, we review the recent advances in understanding the molecular mechanisms regulating osteoblast differentiation and adipocyte differentiation of MSCs and highlight the therapeutic application studies of MSCs in osteoporosis treatment. This will provide researchers with new insights into the development and treatment of osteoporosis.

Keywords: adipocyte; cell therapy; mesenchymal stem cell; osteoblast; osteoporosis.

Figure 1

Schematic diagram of the characteristics of mesenchymal stem cells (MSCs). There are both positive markers and negative markers for identifying MSCs. MSCs possess the characteristics of self-renewing and differentiating into multiple cell types, including osteoblast, adipocyte, chondrocyte, myocyte, and fibroblast.

Figure 2

Integration of bone morphogenic protein (BMP) and wingless and int-1 (Wnt) signaling pathways, miRNAs, and key transcription factors in regulating osteoblast and adipocyte differentiation of MSCs. The BMP signaling, Wnt signaling, and miRNAs regulate osteoblast differentiation or adipocyte differentiation of MSCs by targeting key transcription factors such as runx2, osterix, or PPARγ.