Topography of calcium phosphate ceramics regulates primary cilia length and TGF receptor recruitment associated with osteogenesis.
Topography of calcium phosphate ceramics regulates primary cilia length and TGF receptor recruitment associated with osteogenesis.
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DOI：
10.1016/j.actbio.2017.04.004
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发表时间：
2017-07-15
影响因子：
9.7
通讯作者：
Yuan H
中科院分区：
文献类型：
--
作者：
Zhang J;Dalbay MT;Luo X;Vrij E;Barbieri D;Moroni L;de Bruijn JD;van Blitterswijk CA;Chapple JP;Knight MM;Yuan H
已知合成生物材料的表面形貌在材料驱动的成骨中起作用。最近的研究表明，tgf - β信号也可以启动成骨分化。tgf - β信号需要将tgf - β受体（tgf - β r）募集到初级纤毛。在本研究中，我们假设磷酸钙陶瓷的表面形貌调节干细胞形态、初级纤毛结构和与成骨分化相关的纤毛TGFβR募集。我们开发了一种2D系统，使用两种具有相同化学性质的磷酸三钙（TCP）陶瓷盘。一种样品具有微米尺度的表面形貌（TCP-B，表面结构尺寸较大），另一种样品具有亚微米尺度的表面形貌（TCP-S，表面结构尺寸较小）。在缺乏成骨分化因子的情况下，人骨髓基质细胞（hBMSCs）在TCP-S上的分布比在TCP-B上的分布更广泛，肌动蛋白组织发生改变，初级纤毛的患病率和长度增加。在成骨介质存在的情况下，TCP-S上的纤毛伸长与在玻璃上观察到的相似，随后转化生长因子-β RII （p-TGFβ RII）被募集到纤毛轴突上。在没有其他成骨生长因子的情况下，碱性磷酸酶活性和关键成骨标志物的基因表达表明，这与TCP-S上hBMSCs的成骨分化增强有关。同样，在犬体内肌内植入12周后，TCP-S诱导骨形成，而TCP-B则没有。最有可能的是，磷酸钙陶瓷的表面形貌调节了初级纤毛的长度和与成骨和骨形成相关的p-TGFβ RII的纤毛募集。这种通过初级纤毛调节的生物工程控制成骨可能代表了一种新型的基于生物材料的纤毛治疗在骨科、牙科和颌面外科的应用。合成生物材料的表面形貌在材料驱动成骨中起着重要的作用。本文提供的数据表明，磷酸钙陶瓷的表面形貌调节了间充质间质细胞（如人骨髓间充质间质细胞，hBMSCs）的形态、原代纤毛结构和TGFβR在体外与成骨分化相关的纤毛上的募集。结合体内骨形成，我们的研究结果提出了一种新型的生物材料为基础的纤毛治疗骨科，牙科和颌面外科，通过生物工程控制成骨通过初级纤毛调节。
The surface topography of synthetic biomaterials is known to play a role in material-driven osteogenesis. Recent studies show that TGFβ signalling also initiates osteogenic differentiation. TGFβ signalling requires the recruitment of TGFβ receptors (TGFβR) to the primary cilia. In this study, we hypothesize that the surface topography of calcium phosphate ceramics regulates stem cell morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation. We developed a 2D system using two types of tricalcium phosphate (TCP) ceramic discs with identical chemistry. One sample had a surface topography at micron-scale (TCP-B, with a bigger surface structure dimension) whilst the other had a surface topography at submicron scale (TCP-S, with a smaller surface structure dimension). In the absence of osteogenic differentiation factors, human bone marrow stromal cells (hBMSCs) were more spread on TCP-S than on TCP-B with alterations in actin organization and increased primary cilia prevalence and length. The cilia elongation on TCP-S was similar to that observed on glass in the presence of osteogenic media and was followed by recruitment of transforming growth factor-β RII (p-TGFβ RII) to the cilia axoneme. This was associated with enhanced osteogenic differentiation of hBMSCs on TCP-S, as shown by alkaline phosphatase activity and gene expression for key osteogenic markers in the absence of additional osteogenic growth factors. Similarly, in vivo after a 12-week intramuscular implantation in dogs, TCP-S induced bone formation while TCP-B did not. It is most likely that the surface topography of calcium phosphate ceramics regulates primary cilia length and ciliary recruitment of p-TGFβ RII associated with osteogenesis and bone formation. This bioengineering control of osteogenesis via primary cilia modulation may represent a new type of biomaterial-based ciliotherapy for orthopedic, dental and maxillofacial surgery applications. The surface topography of synthetic biomaterials plays important roles in material-driven osteogenesis. The data presented herein have shown that the surface topography of calcium phosphate ceramics regulates mesenchymal stromal cells (e.g., human bone marrow mesenchymal stromal cells, hBMSCs) with respect to morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation in vitro. Together with bone formation in vivo, our results suggested a new type of biomaterial-based ciliotherapy for orthopedic, dental and maxillofacial surgery by the bioengineering control of osteogenesis via primary cilia modulation.