Fate decision of mesenchymal stem cells: adipocytes or osteoblasts?

Abstract

Mesenchymal stem cells (MSCs), a non-hematopoietic stem cell population first discovered in bone marrow, are multipotent cells capable of differentiating into mature cells of several mesenchymal tissues, such as fat and bone. As common progenitor cells of adipocytes and osteoblasts, MSCs are delicately balanced for their differentiation commitment. Numerous in vitro investigations have demonstrated that fat-induction factors inhibit osteogenesis, and, conversely, bone-induction factors hinder adipogenesis. In fact, a variety of external cues contribute to the delicate balance of adipo-osteogenic differentiation of MSCs, including chemical, physical, and biological factors. These factors trigger different signaling pathways and activate various transcription factors that guide MSCs to commit to either lineage. The dysregulation of the adipo-osteogenic balance has been linked to several pathophysiologic processes, such as aging, obesity, osteopenia, osteopetrosis, and osteoporosis. Thus, the regulation of MSC differentiation has increasingly attracted great attention in recent years. Here, we review external factors and their signaling processes dictating the reciprocal regulation between adipocytes and osteoblasts during MSC differentiation and the ultimate control of the adipo-osteogenic balance.

Type I interferons exert anti-tumor effect via reversing immunosuppression mediated by mesenchymal stromal cells

“…Since various cytokines in the microenvironment of the MSC niche are critical for MSC lineage commitment (17, 18), it is possible that the reversion of MSC immunosuppression by IFNα is due to inducing MSC differentiation. To test this possibility, we treated MSCs with IFNγ and TNFα or IFNγ, TNFα and IFNα for 24 hours.…”

Qualitative Aspects of Bone Marrow Adiposity in Osteoporosis

“…Several fundamental signaling pathways participate in regulating the lineage commitment of MSCs, including transforming growth factor-beta (TGFβ)/bone morphogenic protein (BMP) signaling, wingless type MMTV integration site (Wnt) signaling, Hedgehogs (Hh), Notch, and fibroblast growth factors (FGFs) (31, 32). …”

BMPER Enhances Bone Formation by Promoting the Osteogenesis-Angiogenesis Coupling Process in Mesenchymal Stem Cells

“…After a fracture, bone mesenchymal stem cells (BMSCs) migrate to the injured site and gradually differentiate into osteoblasts, which produce bone matrix and repair the fractured bone [1]. While multiple signaling pathways are involved in regulating BMSC differentiation, bone morphogenetic proteins (BMPs) play a critical role in inducing the differentiation of BMSCs of the osteoblastic lineage and enhancing the differentiated function of osteoblasts [2, 3]. BMP-2, BMP-4, BMP-6, BMP-7 and BMP-9 induce osteogenic differentiation of MSCs in vitro and in vivo [4, 5].…”