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Early BMP, Wnt and Ca(2+)/PKC pathway activation predicts the bone forming capacity of periosteal cells in combination with calcium phosphates

, : Early BMP, Wnt and Ca(2+)/PKC pathway activation predicts the bone forming capacity of periosteal cells in combination with calcium phosphates. Biomaterials 86: 106-118

The development of osteoinductive calcium phosphate- (CaP) based biomaterials has, and continues to be, a major focus in the field of bone tissue engineering. However, limited insight into the spatiotemporal activation of signalling pathways has hampered the optimisation of in vivo bone formation and subsequent clinical translation. To gain further knowledge regarding the early molecular events governing bone tissue formation, we combined human periosteum derived progenitor cells with three types of clinically used CaP-scaffolds, to obtain constructs with a distinct range of bone forming capacity in vivo. Protein phosphorylation together with gene expression for key ligands and target genes were investigated 24 hours after cell seeding in vitro, and 3 and 12 days post ectopic implantation in nude mice. A computational modelling approach was used to deduce critical factors for bone formation 8 weeks post implantation. The combined Ca(2+)-mediated activation of BMP-, Wnt- and PKC signalling pathways 3 days post implantation were able to discriminate the bone forming from the non-bone forming constructs. Subsequently, a mathematical model able to predict in vivo bone formation with 96% accuracy was developed. This study illustrates the importance of defining and understanding CaP-activated signalling pathways that are required and sufficient for in vivo bone formation. Furthermore, we demonstrate the reliability of mathematical modelling as a tool to analyse and deduce key factors within an empirical data set and highlight its relevance to the translation of regenerative medicine strategies.


PMID: 26901484

DOI: 10.1016/j.biomaterials.2016.01.059

Other references

Jeanrenaud P., 1969: Data on the Meotian of Moldavia, Romania. Iasi, Universitatea, Analele Stiintifice(Sectiunea 2, B, Geologie (Serie Noua) (continuation of Iasi, Universitatea, Analele Stiintifice, Sectiunea 2, Stiinte Naturale, B, Geologie-Geografie) Jassy

Allegre C.J.; Shimizu N.; Treuil M., 1977: Comparative chemical history of the Earth, Moon and parent body of achondrite. Philosophical Transactions of the Royal Society of London, Series A: Mathematical and Physical Sciences 285(1327): 55-67

Branny J.; Sainerova H.; Sovova V., 1976: Hem adsorption of human erythrocytes coated with concanavalin a on normal transformed and hybrid cells. Folia Biologica (Prague) 22(1): 20-24

Silberbauer K.; Clopath P.; Sinzinger H.; Schernthaner G., 1980: Effect of experimentally induced diabetes on swine vascular prostacyclin synthesis. Artery 8(1): 30-36

Pozy, P., 1989: Integration of agriculture and animal breeding at family-run farms in Bututsi (Burundi). Animal production results. An account is given of recent attempts at improving the production of milk, meat and dung of cattle in Burundi by means of crossing local cattle with Sahiwals, a reduction in the number of cattle per herd, and improved nutrition and management. Fo...

Wakui, K.; Ito, S.; Yabuki, S.; Kato, T.; Nakano, K., 1970: Case of neuromyelitis optica suspected to be toxoplasmosis. Ganka. Ophthalmology 12(7): 591-601

Colledan, M.; D'Antiga, L., 2015: Biliary complications after pediatric liver transplantation: the endless heel. Pediatric Transplantation 18(8): 786-787

Mwanahamuntu, M.H.; Sahasrabuddhe, V.V.; Kapambwe, S.; Pfaendler, K.S.; Chibwesha, C.; Mkumba, G.; Mudenda, V.; Hicks, M.L.; Vermund, S.H.; Stringer, J.S.A.; Parham, G.P., 2011: Advancing cervical cancer prevention initiatives in resource-constrained settings: insights from the Cervical Cancer Prevention Program in Zambia. Groesbeck Parham and colleagues describe their Cervical Cancer Prevention Program in Zambia, which has provided services to over 58,000 women over the past five years, and share lessons learned from the program's implementation and integratio...

Albrecht, K.; Hart, J.; Shaw, A.; Dunker, A.K., 1996: Quaternion contact ribbons: a new tool for visualizing intra- and intermolecular interactions in proteins. Protein side chain interactions between residues separated by at least one loop or turn or break in the amino acid sequence are called 'nonlocal contacts' in this manuscript, and contiguous sets of such interactions located between segme...

Striker, M.M.; E.A., 1961: Soil survey of Lenawee County, Michigan. U S Dept Agric Soil Conserv Serv Soil Surv 1947(10): 1-62