Liu Hongrui, Feng Wei, Cui Jian, Lv Shengyu, Hasegawa Tomoka, Sun Bao, Li Juan, Oda Kimimitsu, Amizuka Norio, Li Minqi
Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan, China (HL, WF, JC, SL, BS, JL, ML)Department of Advanced Medicine, Graduate School of Medicine (Y), Hokkaido University, Sapporo, JapanDepartment of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine (TH, NA), Hokkaido University, Sapporo, JapanDivision of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (KO).
Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan, China (HL, WF, JC, SL, BS, JL, ML)Department of Advanced Medicine, Graduate School of Medicine (Y), Hokkaido University, Sapporo, JapanDepartment of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine (TH, NA), Hokkaido University, Sapporo, JapanDivision of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (KO)
J Histochem Cytochem. 2014 Aug;62(8):556-64. doi: 10.1369/0022155414537830. Epub 2014 May 14.
Interleukin-6 (IL-6) is a multifunctional cytokine considered to modulate bone homeostasis. Based on previous contradictory studies, we aimed to verify the influence of IL-6 deficiency on bone remodeling using an IL-6 knockout (IL-6-/-) murine model. Eight-month-old male mice, homozygous for the disrupted IL-6 gene, and their wild type (WT) littermates (control), were used. After transcardiac perfusion, tibiae were removed for histochemical analysis. Compared with the control group, IL-6 deficiency increased tartrate resistant acid phosphatase (TRAP)-positive osteoclast numbers and up-regulated the alkaline phosphatase (ALP) activity of osteoblasts in the metaphysis of the tibia. However, further analysis of serial histological sections from IL-6-/- mice found a significant discrepancy in osteoclast number, with the higher number of TRAP-positive osteoclasts conflicting with the lower number of cathepsin K-positive osteoclasts. Moreover, TUNEL staining identified a significantly higher rate of osteoclast apoptosis in IL-6-/- mice as compared with their WT controls. IL-6 deficiency induced abundant TRAP-positive osteoclasts but delayed bone remodeling by significantly inhibiting the bone resorption activity of osteoclasts and promoting osteoclast apoptosis.
白细胞介素-6（IL-6）是一种多功能细胞因子，被认为可调节骨稳态。基于先前相互矛盾的研究，我们旨在使用IL-6基因敲除（IL-6-/-）小鼠模型来验证IL-6缺乏对骨重塑的影响。使用了IL-6基因 disrupted的8个月大的纯合雄性小鼠及其野生型（WT）同窝小鼠（对照）。经心脏灌注后，取出胫骨进行组织化学分析。与对照组相比，IL-6缺乏增加了抗酒石酸酸性磷酸酶（TRAP）阳性破骨细胞数量，并上调了胫骨干骺端成骨细胞的碱性磷酸酶（ALP）活性。然而，对IL-6-/-小鼠连续组织切片的进一步分析发现破骨细胞数量存在显著差异，TRAP阳性破骨细胞数量较多与组织蛋白酶K阳性破骨细胞数量较少相矛盾。此外，TUNEL染色显示，与WT对照相比，IL-6-/-小鼠破骨细胞凋亡率显著更高。IL-6缺乏诱导了大量TRAP阳性破骨细胞，但通过显著抑制破骨细胞的骨吸收活性和促进破骨细胞凋亡而延迟了骨重塑。
