Endocrine Abstracts (2002) 3 P3

Investigation into the plasticity of adult human bone marrow adipocytes

S Ioannidou, W Staley, RJ Byers, PL Selby, AJ Freemont & JA Hoyland

Musculoskeletal Research Group, University of Manchester, Manchester, UK.

Osteoblasts and adipocytes are derived from the same stem cell in adult marrow and plasticity exists between the two lineages. In Osteoporosis there are reduced osteoblast numbers and increased adipocyte numbers suggesting a disturbance in the normal balance of the cells' differentiation pathways, leading to defective osteoblastogenesis and favouring adipogenesis. The stage of adipocytic differentiation at which plasticity is lost and commitment is established is not known. We have recently shown that by changing the environment adipocytic precursors can convert to osteoblasts. This study aims to investigate the ability of mature adipocytes to convert to osteoblasts.

Local Ethical Committee approval was obtained. Mature adipocytes were isolated from the bone marrow sample of a young adult male donor by density gradient centrifugation and cultured (i)in vitro(/i) in adipogenic medium for 7 days. They were then cultured in dedifferentiation medium for 35 days prior to being switched to osteogenic medium or mineralising medium for 14 days. Morphology and histochemical staining for oil red O, alkaline phosphatase and alizarin red S was noted at regular intervals. Mature adipocytes dedifferentiated to fibroblast-like cells and then redifferentiated to osteoblasts and formed mineralised calcium upon appropriate stimulation. In conclusion, by changing the environment mature adipocytes can convert to osteoblasts. Current work is centred on extending these findings by genotypically typing adipocytes and osteoblasts during the switch between the two lineages. We propose that, if the factors responsible for the switch between adipocytes and osteoblasts were identified, they could be used for the development of novel therapeutic intervention in Osteoporosis.

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