title: Beta-tricalcium phosphate exerts osteoconductivity through alpha2beta1 integrin and down-stream MAPK/ERK signaling pathway.
abstract: Beta-tricalcium phosphate (beta-TCP) has been clinically used as a bone graft substitute for decades because of its excellent osteoconductivity. However, the exact mechanism(s) by which beta-TCP exerts osteoconductivity are not fully documented. This study was aimed to investigate the molecular mechanism(s) by which beta-TCP modulates the biological response of primary human osteoblasts (HOBs). It was showed that HOBs seeded into the beta-TCP scaffolds expressed significantly higher levels of osteogenic genes, compared to those cultured on tissue culture plastic; meanwhile these cells showed 7-fold increase in alpha2 integrin subunit gene expression and the activation of the mitogen-activated protein kinase (MAPK)/extracellular related kinase (ERK) signaling pathway. In addition, the osteogenic conduction by beta-TCP scaffolds was attenuated directly by inhibiting MAPK/ERK or indirectly by blocking the alpha2beta1 integrin signaling pathway. We concluded that beta-TCP scaffold exerts osteoconductivity through alpha2beta1 integrin and down-stream MAPK/ERK signaling pathway, suggesting a feasible approach to consider when designing or fabricating the scaffolds for bone tissue engineering.
authors.affiliation: Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney, Sydney 2006, Australia.
authors.forename: Zufu
authors.initials: Z
authors.lastname: Lu
authors.forename: Hala
authors.initials: H
authors.lastname: Zreiqat
mesh_terms: D001861:Bone Regeneration / Q000187:drug effects*; D018786:Bone Substitutes / Q000494:pharmacology*; D002130:Calcium Phosphates / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D015398:Signal Transduction; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D018786:Bone Substitutes; D002130:Calcium Phosphates; D038982:Integrin alpha2beta1; C485817:beta-tricalcium phosphate; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases