張力對於人類巨噬細胞透過RANKL路徑促進噬骨細胞生成作用之探討

目前已經有許多研究是關於細胞和機械力的關係，但是有關於張力對於人類單核球細胞誘發噬骨細胞生成作用，這方面的文章仍然不多，尤其是在沒有機械感受性細胞（例如骨母細胞、纖維母細胞）的狀況下。在本研究中，研究在張力環境下是單獨培養人類單核球細胞，並以RANKL處理後，並觀察其噬骨細胞生成作用。接著開始檢視細胞活性以及組織蛋白酶K（cathepsin K）的表現量。張力的存在會加強RANKL誘發噬骨細胞生成作用，此外也發現在小於-100 kPa張力下，RANKL在提高TRAP活性的表現上，是呈現計量依賴性的（dose-dependent）。張力也會讓RANKL提高組織蛋白酶K的表現以及分泌量，同時增加誘發TRAF6和活化NF-κB。總結來說，現今的研究證明了張力會藉由提高噬骨細胞的分化，來加強RANKL本身的誘發噬骨細胞生成的能力。在體外的RANKL調控噬骨細胞生成實驗中，張力是以計量依賴性的趨勢去調整每種細胞，例如噬骨前驅細胞的融合，以及噬骨細胞的功能。另外，張力也使TRAF6的表現量增加了。雖然這是一個體外實驗所得到的結果，但是對於在人類巨噬細胞轉換成為噬骨細胞的過程，能得到一個更好的解釋方式，同時也讓我們對於張力是如何造成矯正治療中的牙齒移動、甚至是齒槽骨的重塑，能有更好的認識。

Objectives: Little is known about the effects of tensile forces on osteoclastogenesis by human monocyte in the absence of mechanosensitive cells, including osteoblasts and fibroblasts. In this study we consider the effects of tensile force on osteoclastogenesis in human monocytes. Materials and Methods: The cells were treated with RANKL to promote osteoclastgenesis. Then, cell viability, and cathepsin K expression were examined and it was discovered that the tensile force enhances the receptor activation of the NF-ƘB ligand (RANKL) and induces the formation of osteoclasts during the osteoclast differentiation process under continual tensile stress. Results: It was also found that ≤ -150 kPa induces RANKL-enhanced TRAP activity in a dose-dependent manner. Furthermore, an increased tensile force raises the expression and secretion of cathepsin K elevated by RANKL, and is concurrent with the increase of TRAF6 induction and NF-ƘB activation. Overall, the current report demonstrates that tensile force reinforces RANKL-induced osteoclastogenesis by retarding osteoclast differentiation. The tensile force is able to modify every cell through dose-dependent in vitro RANKL-mediated osteoclastogenesis, affecting the fusion of preosteoclasts, and function of osteoclasts. However, tensile force increased TRAF6 expression. Conclusions: These results are in vitro findings and were gained under a condition of tensile force, the current results help us to better understand the cellular roles of human macrophage cell populations in osteoclastogenesis as well as in alveolar bone remodeling when there is tensile stress.