Modulating Temporospatial Phosphate Equilibrium by Nanoparticulate Mineralized Collagen Materials Induces Osteogenesis via PiT-1 and PiT-2.
Modulating Temporospatial Phosphate Equilibrium by Nanoparticulate Mineralized Collagen Materials Induces Osteogenesis via PiT-1 and PiT-2.
复制标题
通过纳米颗粒矿化胶原材料调节时空磷酸盐平衡通过 PiT-1 和 PiT-2 诱导成骨。
DOI：
10.1002/adhm.202202750
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发表时间：
2023
影响因子：
10
通讯作者：
Lee,JustineC
中科院分区：
文献类型：
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作者：
Ren,Xiaoyan;Zhou,Qi;Bedar,Meiwand;Foulad,David;Huang,KellyX;Dejam,Dillon;Dahan,NatalieJ;Kolliopoulos,Vasiliki;Harley,BrendanAC;Lee,JustineC
磷酸盐的时空平衡有助于生理性骨发育和骨折愈合，但在骨骼再生材料中尚未探索磷酸盐含量的最佳控制。纳米颗粒矿化胶原糖胺聚糖（MC-GAG）是一种合成的可调材料，可促进体内颅骨再生。在这项工作中，研究了MC-GAG磷酸盐含量对周围微环境和骨祖细胞分化的影响。本研究发现，MC-GAG与可溶性磷酸盐表现出时间关系，在培养早期洗脱，在有或没有分化的原代骨髓源性人间充质干细胞（hMSC）的情况下转变为吸收。MC-GAG的固有磷酸盐含量足以刺激hMSC在基础生长培养基中的成骨分化，而不添加外源性磷酸盐，其方式可以通过敲低磷酸钠转运蛋白PiT-1或PiT-2而严重减少，但不会消除。PiT-1和PiT-2对MC-GAG-介导的成骨的贡献是非冗余的，但也是非累加的，表明异二聚体形式对其活性至关重要。这些发现表明，MC-GAG的矿物质含量改变了局部微环境中的磷酸盐浓度，导致祖细胞通过PiT-1和PiT-2进行成骨分化。
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.