Am J Stem Cell 2012;1(3):205-224

Review Article
Regulatory pathways associated with bone loss and bone marrow adiposity caused
by aging, chemotherapy, glucocorticoid therapy and radiotherapy

Kristen R Georgiou, Susanta K Hui, Cory J Xian

Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001,
Australia; Department of Therapeutic Radiology, College of Medicine, University of Minnesota, Minneapolis, MN 55455, USA

Received September 1, 2012; Accepted September 21, 2012; Epub November 30, 2012; Published December 10, 2012

Abstract: The bone marrow is a complex environment that houses haematopoietic and mesenchymal cell populations and regulates
bone turnover throughout life. The high proliferative capacity of these cell populations however, makes them susceptible to damage and
injury, altering the steady-state of the bone marrow environment. Following cancer chemotherapy, irradiation and long-term
glucocorticoid use, reduced bone and increased fat formation of marrow stromal progenitor cells results in a fatty marrow cavity, reduced
bone mass and increased fracture risk. These bone and marrow defects are also observed in age-related complications such as
estrogen deficiency and increased oxidative stress. Although the underlying mechanisms are yet to be clarified, recent investigations
have suggested a switch in lineage commitment of bone marrow mesenchymal stem cells down the adipogenic lineage at the expense
of osteogenic differentiation following such stress or injury. The Wnt/β-catenin signalling pathway is however has been recognized the
key mechanism regulating stromal commitment, and its involvement in the osteogenic and adipogenic lineage commitment switch
under the damaging conditions has been of great interest. This article reviews the effects of various types of stress or injury on the
commitment to the adipogenic and osteogenic lineages of bone marrow stromal progenitor cells, and summarizes the roles of the Wnt/β-
catenin and associated signalling pathways in the lineage commitment, switch, and recovery after damage, and as a therapeutic target.

Keywords: Bone marrow, mesenchymal stem cells, osteogenesis, adipogenesis, ageing, oxidative stress, chemotherapy, radiotherapy,
glucocorticoids, Wnt/β-catenin signalling

Address all correspondence to:
Dr. Cory J Xian
Sansom Institute for Health Research
University of South Australia
City East Campus, GPO Box 2471
Adelaide 5001, Australia.
Phone: (618) 8302 1944; Fax: (618) 8302 1087
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