Oka Hiroko, Kitagawa Masae, Takata Takashi
Department of International Collaboration Development for Dentistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
J Periodontol. 2015 Mar;86(3):465-72. doi: 10.1902/jop.2014.140419. Epub 2014 Oct 9.
F-spondin, known to be a secreted neuronal glycoprotein, is highly expressed on the tooth root surface. The authors previously reported that F-spondin is one of the specific markers of cementoblasts in periodontal tissue. In chronic periodontitis, significant cemental resorption rarely occurs on the root side, although alveolar bone resorption by osteoclasts is one of the major pathologic changes. Thus, it was hypothesized that secretory F-spondin from cementoblasts might be involved in differentiation of clastic cells on the root surface. The authors studied effects of secretory F-spondin from F-spondin-expressing cells and its pathway on receptor activator of nuclear factor-κB ligand (RANKL)-mediated differentiation of clastic cells.
Osteoclast precursors were used in this study. With a chamber assay, the authors examined effects of secretory molecules from F-spondin-expressing cells of transgenic mice on RANKL-induced clastic cell differentiation.
Secretory molecules from F-spondin-overexpressing cells significantly inhibited the RANKL-mediated tartrate-resistant acid phosphatase (TRAP)-positive cells from primary progenitor cells with the chamber system. F-spondin suppressed RANKL-mediated nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1); TRAP; cathepsin K; and dendritic cell-specific transmembrane protein (DC-STAMP) expression in the cells. The suppressive effect of F-spondin on RANKL-induced differentiation of clastic cells was partially blocked by knockdown of low-density lipoprotein receptor-related protein 8 (LRP8).
These findings indicate that secretory factors from F-spondin-expressing cells, including F-spondin, downregulate differentiation of clastic precursors. Moreover, F-spondin inhibits RANKL-mediated differentiation of clastic cells partially via LRP8. It is suggested that secretory F-spondin may act protectively from cemental resorption partially via LRP8 in periodontal tissue.
F-spondin是一种已知的分泌型神经元糖蛋白，在牙根表面高度表达。作者之前报道F-spondin是牙周组织中牙骨质细胞的特异性标志物之一。在慢性牙周炎中，尽管破骨细胞引起的牙槽骨吸收是主要病理变化之一，但牙根侧很少发生明显的牙骨质吸收。因此，推测牙骨质细胞分泌的F-spondin可能参与牙根表面破骨细胞的分化。作者研究了表达F-spondin的细胞分泌的F-spondin及其信号通路对核因子κB受体活化因子配体（RANKL）介导的破骨细胞分化的影响。
本研究使用破骨细胞前体。通过小室试验，作者检测了转基因小鼠中表达F-spondin的细胞分泌分子对RANKL诱导的破骨细胞分化的影响。
在小室系统中，过表达F-spondin的细胞分泌分子显著抑制了RANKL介导的原代祖细胞中抗酒石酸酸性磷酸酶（TRAP）阳性细胞的生成。F-spondin抑制细胞中RANKL介导的活化T细胞核因子细胞质1（NFATc1）、TRAP、组织蛋白酶K和树突状细胞特异性跨膜蛋白（DC-STAMP）的表达。低密度脂蛋白受体相关蛋白8（LRP8）的敲低部分阻断了F-spondin对RANKL诱导的破骨细胞分化的抑制作用。
这些发现表明，包括F-spondin在内的表达F-spondin的细胞分泌因子可下调破骨前体细胞的分化。此外，F-spondin部分通过LRP8抑制RANKL介导的破骨细胞分化。提示分泌型F-spondin可能在牙周组织中部分通过LRP8对牙骨质吸收起到保护作用。
