Kidney and Metabolic Bone Diseases Vol.19 No.4(2-1)

Theme Bone tissue regeneration
Title An osteogenic differentiation cascade of mesenchymal stem cells
Publish Date 2006/10
Author Yoshiko Dohi Department of Public Health Policy, Nara Medical University School of Medicine
[ Summary ] Bone marrow contains pluripotent stem cells of the adipocytic, chondrocytic, and osteoblastic cell lineages. In vitro proliferated marrow mesenchymal stem cells (MSCs) can further differentiate into bone forming osteoblasts. They formed mineralized nodules, when subcultured in the presence of dexamethasone, ascorbic acid, and β-glycerophosphate.
Using a two-step tissue engineering technique, ex vivo fabricated osteoblast / biomaterials aid in therapy for hard tissue repair, once materials are coated with bone matrix by osteoblasts derived from patients' MSCs.
MSC-derived osteoblasts progress through a three stage process of differentiation : proliferation, matrix production, and mineralization. These differentiation and bone formation processes are largely mediated by various cytokines such as BMP-2, transcriptional factors, Cbfa1 and osterix, neighboring mature cells, along with extracellular matrix proteins, whose expression is strictly controlled both spatially and temporally.
The bone matrix is composed primarily of type I collagen, which forms an extracellular matrix for the deposition of hydroxyapatite, and non-collagenous proteins. Cellular mRNA levels of alkaline phosphatase (ALP), osteopontin and osteocalcin increased concomitantly with the development of bone nodules. Computer assisted confocal laser scanning microscopy analysis showed in vitro bone tissue consisting of layers of mineralized matrix with round cells in the matrix lacunae, osteoid, and osteoblasts on the osteoid surface.
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