Plasticity and regulation of human bone marrow stromal osteoprogenitor cells: potential implication in the treatment of age-related bone loss.
Human bone marrow stroma contains pluripotent mesenchymal progenitor cells that can give rise to many mesenchymal lineages, including chondroblasts, adipocytes or osteoblasts. The differentiation of these cells towards a specific lineage is dependent on hormonal and local factors activating specific transcription factors. Attempts have been recently made to identify osteoprogenitor cells in the human bone marrow and to identify the molecular mechanisms responsible for lineage-specific differentiation of human bone marrow stromal cells. Using a clonal pluripotent human bone marrow stromal cell line with tri-potential characteristics, we have provided evidence for a controlled reciprocal regulation of osteoblast/chondroblast and osteoblast/adipocyte differentiation of human bone marrow stromal cells. We have also shown that administration of TGFss that regulates the expression of specific osteoblast and adipocyte transcription factors can promote osteoblast differentiation and inhibit adipocyte conversion of rat marrow stromal cells in vivo. This indicates that the reciprocal relationship between osteoblastogenesis and adipogenesis can be manipulated in vivo in order to improve bone formation. Future studies will have to identify key signals for lineage-specific differentiation of human marrow stromal cells. This may result in the development of therapeutic strategies to promote the differentiation of these cells towards the osteoblast lineage and to inhibit excessive bone marrow adipogenesis associated with aging.
Ahdjoudj
S
S
Laboratory of Osteoblast Biology and Pathology, INSERM Unité 349 affiliated to CNRS, Paris Cedex 10, France.
Fromigué
O
O
Marie
P J
PJ
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000375:Aging; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000473:pathology / Q000628:therapy*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000633:toxicity
D014157:Transcription Factors; D016212:Transforming Growth Factor beta