矽酸鈣材料抑制蝕骨細胞分化及促進牙本質再生機制探討

矽離子是一種存在於健康骨組織與結締組織間所必須的微量元素。目前，已發展出多種矽基底材料，如生物活性玻璃、矽取代氫氧基磷灰石、矽取代α–三鈣磷酸鹽、與其他多相型系統。然而，矽誘導細胞功能之最佳濃度並未被明確定義。因此，本研究主要目的為探討由矽酸鈣陶瓷釋放出的矽離子濃度對於細胞行為之影響。研究結果顯示，當巨嗜細胞（Raw264.7）培養在含有矽離子（≤ 4 mM）之培養液中，細胞增生量並不會受到細離子濃度的增加而改變。然而，矽離子可以有效抑制RANKL的活化進而影響蝕骨細胞的分化，並且具有濃度的效應。此外，矽離子藉由降低RANKL來影響組織蛋白酶K的表現和分泌，並且同時抑制TRAF6與NF-ƘB活化。因此，對不同的細胞附著，增殖和分化的行為仍然取決於材料表面的化學性質。為了讓矽基底材料有更廣泛的應用，了解矽離子刺激細胞貼附與增生的機制是很重要的。因此另外使用人類初代牙髓細胞評估細胞在矽酸鈣骨水泥及三鈣磷酸鹽骨水泥上的表現差異。相對於三鈣磷酸鹽骨水泥，矽酸鈣可以藉由釋放出矽離子增加細胞分泌纖連蛋白（fibronectin，FN），並且加速細胞的貼附效果。矽酸鈣水泥也可促進FN和αV子整合表達。並且在FN吸附效果以及整合素的表現上，三鈣磷酸鹽與控制組是相似的。此外，牙髓細胞經過小片段RNA的處理後在培養於矽酸鈣上可以有效抑制細胞的生長以及牙本質蛋白的活性。在本研究中指出，矽酸鈣可以藉由抑制RANKL誘導破骨細胞的路徑來降低蝕骨細胞分化的表現。此外，矽基底材料也可以藉由材料的成分來影響控制整合素的表現，以用來作為一種調節細胞於生物材料表面的主要機制。

關鍵字

矽酸鈣水泥；蝕骨細胞分化；整合素；細胞材料界面；牙本質分化

並列摘要

Si ion is an essential trace element required for healthy bone and connective tissues. The silicon-base material such as bioglass, Si substituted HA (Si-HA), Si substituted α-TCP (Si-α-TCP), and other multiphase systems were developed. The optimal concentration at which Si induces cell functions has not been fully elucidated. In the present study the effects of Si concentration release from calcium silicate cement on the biological. Raw264.7 cell proliferation in the presence of 2 mM Si- and 4 mM Si-containing media was no affected with increasing culture time. However, the Si inhibited receptor activator of the NF-ƘB ligand (RANKL) induced formation of osteoclasts during the osteoclast differentiation process. It was also found that ≥ 2 mM Si reduced RANKL-enhanced TRAP activity in a dose-dependent manner. Furthermore, Si diminished the expression and secretion of cathepsin K elevated by RANKL, and was concurrent with the inhibition of TRAF6 induction and NF-ƘB activation. Therefore, cell attachment, proliferation, and differentiation behaviors on different materials depend on the surface properties of the material. Unraveling the mechanism of Si-induced cell attachment and proliferation enhancement is important to expand the applications of silica-based materials. The purpose of this study was to investigate the responses of human dental pulp cells (hDPCs) to calcium silicate (CS) cements and tricalcium phosphate cement (TCP). CS releases Si ion increased FN secretion and adsorption, which promote cell attachment more effectively than TCP. The CS cement facilitates FN and αv sub-integrin expression. However, the FN adsorption and integrin expression of TCP are similar to that observed in the control dish. In addition, the proliferation and odontogenic activity was carefully monitored as it degraded in the siRNA-treated cells on CS over a period of 14 days. The current report demonstrates that silicate abrogated RANKL induced osteoclastogenesis by retarding osteoclast differentiation. The Si can modulate every cell through dose-dependent in vitro RANKL-mediated osteoclastogenesis, such as the proliferation and fusion of preosteoclasts, and the function of osteoclasts. The silicate-based materials may be a potential therapeutic agent targeting osteoclast differentiation in bone defect. In addition, the composition-dependent differences in integrin binding, and its effectiveness as a mechanism regulating cellular responses to biomaterial surface.

並列關鍵字

Calcium silicate cement ； osteoclastgenesis ； integrin ； cell-material interface ； odontogenesis

參考文獻

[2] Petty W. The effect of methylmethacrylate on chemotaxis of polymorphonuclear leukocytes. J Bone Joint Surg Am 1978;60:492–8.

[3] Skripitz R, Aspenberg P. Attachment of PMMA cement to bone: force measurements in rats. Biomaterials 1999;20:351–6.

[4] Barralet J, Grover L, Gaunt T, Wright A, Gibson I. Preparation of macroporous calcium phosphate cement tissue engineering scaffold. Biomaterials 2002;23:3063–72.

[5] Chow L. Calcium phosphate materials: reactor response. Adv Dent Res 1988;2:181–6.

[6] Carlisle E. Silicon: a possible factor in bone calcification. Science 1970;167:279–80.

國際替代計量

矽酸鈣材料抑制蝕骨細胞分化及促進牙本質再生機制探討

未授權

主題瀏覽