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EXPRESSION OF OSTEOBLASTIC DIFFERENTIATION MARKERS AND MATRIX SYNTHESIS FOLLOWING ADENOVIRAL TRANSFER OF TGF-β1 CDNA INTO MURINE AND HUMAN BONE MARROW STROMAL CELLS



Abstract

TGF-β1 and BMP-2 are abundant proteins in bone matrix, their interaction in controlling osteoblastic differentiation is, however, not clearly understood. To gain more insight into the role of TGF-β1 in the control of osteoblastic differentiation, murine and human bone marrow stromal cells were transduced with an adenovirus carrying the human TGF-β1 cDNA or LacZ gene. The transduced cells assessed for alkaline phosphatase(ALP) activity, cell proliferation and matrix synthesis. The murine TGF-β1 transduced cells synthesized and secreted about 25 ng/ml of TGF-β1, while the human cells secreted about 120 ng/ml of TGF-β1 over 24h. Both the murine and human TGF-β1 transduced cells failed to respond to rhBMP-2 as indicated by non-expression of ALP activity, while the LacZ transduced cells expressed ALP activity under similar conditions. Treatment of the bone stromal cells with the human TGF-β1 protein in presence of BMP-2 demonstrated that the inhibition of the ALP activity expression is dose dependent.

The abstracts were prepared by Professor Jegan Krishnan. Correspondence should be addressed to him at the Flinders Medical Centre, Bedford Park 5047, Australia.