title: Magnesium modification up-regulates the bioactivity of bone morphogenetic protein-2 upon calcium phosphate cement via enhanced BMP receptor recognition and Smad signaling pathway.
abstract: Efficient presentation of growth factors is one of the great challenges in tissue engineering. In living systems, bioactive factors exist in soluble as well as in matrix-bound forms, both of which play an integral role in regulating cell behaviors. Herein, effect of magnesium on osteogenic bioactivity of recombinant human bone morphogenetic protein-2 (rhBMP-2) was investigated systematically with a series of Mg modified calcium phosphate cements (xMCPCs, x means the content of magnesium phosphate cement wt%) as matrix model. The results indicated that the MCPC, especially 5MCPC, could promote the rhBMP-2-induced in vitro osteogenic differentiation via Smad signaling of C2C12 cells. Further studies demonstrated that all MCPC substrates exhibited similar rhBMP-2 release rate and preserved comparable conformation and biological activity of the released rhBMP-2. Also, the ionic extracts of MCPC made little difference to the bioactivity of rhBMP-2, either in soluble or in matrix-bound forms. However, with the quartz crystal microbalance (QCM), we observed a noticeable enhancement of rhBMP-2 mass-uptake on 5MCPC as well as a better recognition of the bound rhBMP-2 to BMPR IA and BMPR II. In vivo results demonstrated a better bone regeneration capacity of 5MCPC/rhBMP-2. From the above, our results demonstrated that it was the Mg anchored on the underlying substrates that tailored the way of rhBMP-2 bound on MCPC, and thus facilitated the recognition of BMPRs to stimulate osteogenic differentiation. The study will guide the development of Mg-doped bioactive bone implants for tissue regeneration.
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Sai
authors.initials: S
authors.lastname: Ding
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tian
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Baolin
authors.initials: B
authors.lastname: Huang
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China. Electronic address: yyuan@ecust.edu.cn.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China; Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China. Electronic address: liucs@ecust.edu.cn.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Liu
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry* / Q000494:pharmacology*; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism*; D002130:Calcium Phosphates / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D008274:Magnesium / Q000737:chemistry* / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C020243:calcium phosphate; D052004:Bone Morphogenetic Protein Receptors; D008274:Magnesium
keywords: Bioactivity; Bone morphogenetic protein-2; Calcium phosphate cement; Magnesium; Smad signaling pathway