Bone morphogenetic protein-9 binds to liver cells and stimulates proliferation

Jeffrey J. Song, Anthony J. Celeste, Feng Ming Kong, Randy L. Jirtle, Vicki Rosen, R. Scott Thies

Research output: Contribution to journalArticlepeer-review

156 Scopus citations


A new member of the transforming growth factor (TGF)-β superfamily, BMP-9, has recently been identified and shown to be expressed in the developing mouse liver. This report demonstrates that human HepG2 liver tumor cells bind recombinant human BMP-9 (rhBMP-9) with high affinity. Cross-linking analysis indicates that HepG2 cells express two BMP-9 receptors of approximately 54 and 80 kilodaltons, similar in size to the Type I and Type II receptors reported by others for TGF-β and BMP-4. However, cross-competition experiments demonstrate that the BMP-9 receptors on HepG2 cells do not bind other BMPs or TGF-β s, indicating that these are novel receptors with binding specificity for BMP-9. In functional studies, rhBMP-9 stimulates HepG2 cell proliferation as indicated by [3H]thymidine incorporation and cell counting assays. A proliferative effect of rh-BMP-9 was also observed on primary rat hepatocytes. In contrast, TGF-β had no effect on HepG2 cell proliferation and inhibited proliferation in primary hepatocytes. These results suggest that BMP-9, acting through a novel set of receptors, may play a regulatory role in hepatic growth and function.

Original languageEnglish (US)
Pages (from-to)4293-4297
Number of pages5
Issue number10
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Endocrinology


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