@article{632dafb1044c46778e0ba3a3aec393fe,
title = "Modulating Temporospatial Phosphate Equilibrium by Nanoparticulate Mineralized Collagen Materials Induces Osteogenesis via PiT-1 and PiT-2",
abstract = "The temporospatial equilibrium of phosphate contributes to physiological bone development and fracture healing, yet optimal control of phosphate content has not been explored in skeletal regenerative materials. Nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) is a synthetic, tunable material that promotes in vivo skull regeneration. In this work, the effects of MC-GAG phosphate content on the surrounding microenvironment and osteoprogenitor differentiation are investigated. This study finds that MC-GAG exhibits a temporal relationship with soluble phosphate with elution early in culture shifting to absorption with or without differentiating primary bone marrow-derived human mesenchymal stem cells (hMSCs). The intrinsic phosphate content of MC-GAG is sufficient to stimulate osteogenic differentiation of hMSCs in basal growth media without the addition of exogenous phosphate in a manner that can be severely reduced, but not eliminated, by knockdown of the sodium phosphate transporters PiT-1 or PiT-2. The contributions of PiT-1 and PiT-2 to MC-GAG-mediated osteogenesis are nonredundant but also nonadditive, suggestive that the heterodimeric form is essential to its activity. These findings indicate that the mineral content of MC-GAG alters phosphate concentrations within a local microenvironment resulting in osteogenic differentiation of progenitor cells via both PiT-1 and PiT-2.",
keywords = "bone regeneration, nanoparticulate mineralized collagen glycosaminoglycan scaffolds, phosphate",
author = "Xiaoyan Ren and Qi Zhou and Meiwand Bedar and David Foulad and Huang, {Kelly X.} and Dillon Dejam and Dahan, {Natalie J.} and Vasiliki Kolliopoulos and Harley, {Brendan A.C.} and Lee, {Justine C.}",
note = "This work was supported by the National Institutes of Health/National Institute of Dental and Craniofacial Research under Award Nos. R01 DE029234 (J.C.L.), R01 DE028098 (J.C.L.), R01 DE030491 (B.A.C.H.), the American Society of Maxillofacial Surgeons/Maxillofacial Foundation (20180247 to D.F.), the Bernard G. Sarnat Endowment for Craniofacial Biology (J.C.L.), and the Jean Perkins Foundation (J.C.L.). The authors are also grateful for funds provided by the NSF Graduate Research Fellowship (DGE‐1746047, V.K.) and the Chemistry‐Biology Interface Research Training Program at the University of Illinois (T32 GM136629, V.K.). The authors wish to acknowledge Ignatio Martini, Ph.D., from the UCLA Department of Chemistry and Biochemistry Materials Characterization Laboratory for his assistance on the X‐ray photoelectron spectroscopy experiments, and Siavash Jalal, Ph.D., from the Office of Advanced Research Computing in the UCLA Institute of Digital Research and Education for statistical consultation. This work was supported by the National Institutes of Health/National Institute of Dental and Craniofacial Research under Award Nos. R01 DE029234 (J.C.L.), R01 DE028098 (J.C.L.), R01 DE030491 (B.A.C.H.), the American Society of Maxillofacial Surgeons/Maxillofacial Foundation (20180247 to D.F.), the Bernard G. Sarnat Endowment for Craniofacial Biology (J.C.L.), and the Jean Perkins Foundation (J.C.L.). The authors are also grateful for funds provided by the NSF Graduate Research Fellowship (DGE-1746047, V.K.) and the Chemistry-Biology Interface Research Training Program at the University of Illinois (T32 GM136629, V.K.). The authors wish to acknowledge Ignatio Martini, Ph.D., from the UCLA Department of Chemistry and Biochemistry Materials Characterization Laboratory for his assistance on the X-ray photoelectron spectroscopy experiments, and Siavash Jalal, Ph.D., from the Office of Advanced Research Computing in the UCLA Institute of Digital Research and Education for statistical consultation.",
year = "2023",
month = jul,
day = "6",
doi = "10.1002/adhm.202202750",
language = "English (US)",
volume = "12",
journal = "Advanced Healthcare Materials",
issn = "2192-2640",
publisher = "John Wiley & Sons, Ltd.",
number = "17",
}