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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
The induction of bone formation by the recombinant human transforming growth factor-β
3
Biomaterials, Volume 35, No. 9, Year 2014
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Description
Implantation of recombinant human transforming growth factor-β3 (hTGF-β3) with coral-derived calcium carbonate-based macroporous bioreactors with limited conversion to hydroxyapatite (7% HA/CC) in the rectus abdominis muscle of the non-human primate Chacma baboon Papio ursinus induces endochondral bone formation. The exact mechanisms by which hTGF-β3 signalling induces bone in heterotopic sites of P.ursinus are not known. Coral-derived 7% HA/CC bioreactors with and without 125μg hTGF-β3 were implanted in triplicate in the rectus abdominis muscle of 6 adult baboons. 7% HA/CC bioreactors either with or without hTGF-β3 were loaded with 125μg of recombinant human Noggin (hNoggin), a bone morphogenetic proteins (BMPs) antagonist. Tissues on day 15, 60 and 90 were analysed by histomorphometry and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Down-regulation of BMP-2 characterized 7% HA/CC constructs preloaded with 125μg hNoggin with Noggin down-regulated on day 60 and 90 together with lack of TGF-β3 expression. Down-regulation of BMP-2 correlated with minimal bone formation by induction. hTGF-β3/hNoggin pre-treated bioreactors up-regulated BMP-2 but only on day 90 together with a significant down-regulation of Noggin on day 60 and 90, correlating with the induction of bone formation, albeit limited, on day 90 at the periphery of the macroporous bioreactors only. hTGF-β3 treated bioreactors significantly down-regulated BMP-2 on day 15 whilst up-regulating BMP-2 on day 60 and 90, together with down-regulation of Noggin on day 60 and 90 correlating with the prominent induction of bone formation. hTGF-β3 significantly up-regulated RUNX-2 and Osteocalcin expression on day 15 controlling the differentiation of progenitor stem cells into the osteoblastic lineage. The induction of bone as initiated by hTGF-β3 in the rectus abdominis muscle of P.ursinus is via the BMPs pathway with hTGF-β3 controlling the induction of bone formation by regulating the expression of BMPs via Noggin expression. These results unequivocally demonstrate that hTGF-β3 elicits bone induction by up-regulation of endogenous BMP-2 and is blocked by hNoggin. © 2013 Elsevier Ltd.
Authors & Co-Authors
Klar, Roland Manfred
South Africa, Johannesburg
School of Clinical Medicine
Duarte, R. A.B.
South Africa, Johannesburg
University of the Witwatersrand
Dix-Peek, Thérèse
South Africa, Johannesburg
University of the Witwatersrand
Ripamonti, Ugo
South Africa, Johannesburg
School of Clinical Medicine
Statistics
Citations: 47
Authors: 4
Affiliations: 2
Identifiers
Doi:
10.1016/j.biomaterials.2013.12.062
ISSN:
01429612
e-ISSN:
18785905
Research Areas
Cancer
Study Approach
Quantitative