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Title: Monocytes promote osteogenic differentiation of mesenchymal stem cells
Author: Nicolaidou, Vicky
ISNI:       0000 0004 2710 2306
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
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Bone loss is a characteristic of many chronic inflammatory and degenerative diseases such as rheumatoid arthritis and osteoporosis. A major challenge is how to replace bone once it is lost. It is known that the immune system strongly regulates bone and investigations into these interactions have demonstrated that osteoclasts, the bone resorbing cells, are strongly regulated by the immune system. However, less is known about the regulation of osteoblasts, the bone forming cells. Mesenchymal stem cells are multipotent progenitors that can be induced in culture to form osteoblasts. The aim of this study was to investigate whether immune cells also regulate OB differentiation. Using in vitro cell cultures of human bone marrow-derived MSCs it was shown that monocytes/Mφs potently induced MSC differentiation to OBs evidenced by increased alkaline phosphatase and mineralisation. However, the ability of monocyte/Mφs to promote osteogenesis differed between CD14++CD16- and CD14+CD16+ monocyte subset as well as M-CSF and GM-CSF Mφs when activated; the CD16- monocytes and M-CSF Mφs still promoted differentiation whereas the CD16+ monocytes and GM-CSF Mφs inhibited it. The monocyte osteogenic effect was mediated by monocyte-derived soluble factors and required STAT3 signalling as well as COX2 upregulation and the production of PGE2. Finally, gene profiling microarray identified Oncostatin M as the mediator of monocyte-induced osteogenesis. This study established a role for monocyte/Mφs as critical regulators of osteogenic differentiation via OSM and STAT3 signalling. It also provides an insight into the interactions between MSCs and monocyte/Mφs in an inflammatory setting where OB differentiation will depend on the balance between pro-inflammatory versus anti-inflammatory monocyte/Mφs.
Supervisor: Horwood, Nikki Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral