Signal transduction pathways controlling the induction of bone formation by macroporous biomimetic matrices
Date
2015-03-27
Authors
Klar, Roland Manfred
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Abstract
In spite of vigorous research efforts to date the induction of bone formation by
macroporous coral-derived constructs when implanted heterotopically in the rectus
abdominis muscle of the non-human primate Chacma baboon Papio ursinus has not yet
been resolved and needs to be assigned. More importantly, the apparent redundancy of
molecular signals singly initiating the induction of bone formation in primate species and
the heterotopic induction of endochondral bone formation by the mammalian recombinant
human transforming growth factor –β3 (rhTGF-β3) isoform have not yet been assigned and
need to be mechanistically resolved. Using the rectus abdominis muscle of Papio ursinus
the study sought to molecularly determine how coral-derived macroporous constructs and
doses of the hTGF-β3 isoform initiate the induction of bone formation. To elucidate the
function of osteoclastogenesis and Ca2+, biomimetic coral-derived 7%
hydroxyapatite/calcium carbonate (7% HA/CC) devices were supplemented either with
240 μg zoledronate bisphosphonate, an osteoclast binding antagonist, or 500 μg of the
calcium channel blocker verapamil hydrochloride. Additionally but in separate coralderived
bioreactors, 125 μg rhTGF-β3 and/or 125 μg hNoggin were added to answer the
question of how TGF-β3 induces bone formation. All devices were then subsequently
implanted within heterotopic sites of the rectus abdominis muscle of 6 Papio ursinus and
left in vivo for 15, 60 and 90 days. Harvested specimens were subjected to
histomorphometrical and quantitative reverse transcription polymerase chain reaction
(qRT-PCR) analysis. Collagen Type IV expression supported by extensive vascularisation
was detected and observed respectively in all implants after 15 days in vivo. Importantly
the zoledronate treated specimens possessed delayed tissue patterning and morphogenesis,