Molecular Changes During Early Phases of Ectopic Bone Regeneration

Bone marrow stem cells can differentiate into various lineages and have tremendous potential for cell therapy and tissue engineering. Objectives: The aim of the present study was to investigate gene expression during early phases of bone regeneration using full fresh marrow transplants in cylindrical scaffolds of demineralized bone matrix (DBM), in-vivo. Methods: Full fresh bone marrow was removed from 2 month old DA rat's femur and transferred into DBM cylinders with no intervening procedures and implanted immediately at subcutaneous thoracic region of the rat. RNA harvested from day 7 and 12 of implanted BM into DBM were analyzed on Affymetrix gene array. Results: An "ossicle" develops spontaneously from the transplanted bone marrow in 3 to 4 weeks, composed of cortical bone, trabecular bone and newly formed bone marrow. The gene expression from analyzed implanted tissues on day 7 and 12 of development expressed an increase in bone development genes like PTH receptor 1, osteocalcin, sialoprotein, bone inducing protein, thyroid hormone receptor, matrix metalloproteinases, bone morphogenetic protein 3, NOV protein and core binding factor 1. Conclusion: This in-vivo ectopic bone regeneration model enables to follow gene expression in early phases of bone formation. Bone regeneration following marrow transplantation is accompanied by down regulation of master genes in muscle differentiation pathway.