Signal transduction pathways controlling the induction of bone formation by macroporous biomimetic matrices

• Main Author: Klar, Roland Manfred
• Format: Others
• Language: en
• Published: 2015
• Subjects: Bone and Bones; Osteogenesis; Papio
• Online Access: http://hdl.handle.net/10539/17353

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,