Journal
NATURE BIOTECHNOLOGY
Volume 18, Issue 9, Pages 954-958Publisher
NATURE AMERICA INC
DOI: 10.1038/79439
Keywords
osteogenesis; bone-formation; ex vivo; three-dimensional; tissue aggregates
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Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL059495] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL 59495] Funding Source: Medline
- NIA NIH HHS [AG 43460] Funding Source: Medline
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Tissue engineering of human bone is a complex process, as the functional development of bone cells requires that regulatory signals be temporally and spatially ordered. The role of three-dimensional cellular interactions is well understood in embryonic osteogenesis, but in vitro correlates are lacking. Here we report that in vitro serum-free transforming growth factor (TGF)-beta 1 stimulation of osteogenic cells immediately after passage results in the formation of three-dimensional cellular condensations (bone cell spheroids) within 24 to 48 hours. In turn, bone cell spheroid formation results in the up-regulation of several bone-related proteins (e.g., alkaline phosphatase, type I collagen, osteonectin) during days 3-7, and the concomitant formation of micro-crystalline bone. This system of ex vivo bone formation should provide important information on the physiological, biological and molecular basis of osteogenesis.
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