Mechanical loading prevents the stimulating effect of IL-1β on osteocyte-modulated osteoclastogenesis
Mechanical loading prevents the stimulating effect of IL-1β on osteocyte-modulated osteoclastogenesis
复制标题
DOI：
10.1016/j.bbrc.2012.02.099
复制
发表时间：
2012-03-30
影响因子：
3.1
通讯作者：
Klein-Nulend, Jenneke
中科院分区：
文献类型：
--
作者：
Kulkarni, Rishikesh N.;Bakker, Astrid D.;Klein-Nulend, Jenneke
炎症性疾病，如类风湿性关节炎，通常伴随着血浆和滑液中白细胞介素1β(IL-1β)水平的升高，以及骨吸收的增加。由于已知骨细胞可以调节骨吸收以响应机械刺激的变化，我们研究了在有或没有机械载荷的情况下，IL-1β是否影响骨细胞调节的破骨细胞生成。将MLO-Y4骨细胞与IL-1β(0.1-1 ng/ml)预先孵育24 h，细胞在有或没有受到1h脉动流体(PFF：0.7+/-0.3 Pa5 Hz)机械载荷的情况下，加入IL-1β(0.1-1 ng/ml)。在PFF或静态培养1h后收集条件培养液。随后，将小鼠骨髓细胞接种于经IL-1β处理的骨细胞上，以确定破骨细胞的形成。将机械加载或静态IL-1β处理的骨细胞的条件培养液加入未处理的骨细胞和小鼠骨髓细胞的共培养中。用IL-1β和静态1L-1β处理的骨细胞条件培养液培养破骨细胞，检测核因子kappaB受体激活剂(RANKL)和骨保护素(OPG)基因的表达。然而，机械负载IL-1β处理的骨细胞的条件培养液阻止了破骨细胞的形成。IL-1β可上调静态骨细胞RANKL的表达，下调OPG基因的表达。本研究结果提示，IL-1β可促进骨细胞调节的破骨细胞生成，而骨细胞的机械负荷可阻断IL-1β诱导的破骨细胞生成。(C)2012 Elsevier Inc.保留所有权利。
Inflammatory diseases such as rheumatoid arthritis are often accompanied by higher plasma and synovial fluid levels of interleukin-1 beta (IL-1 beta), and by increased bone resorption. Since osteocytes are known to regulate bone resorption in response to changes in mechanical stimuli, we investigated whether IL-1 beta affects osteocyte-modulated osteoclastogenesis in the presence or absence of mechanical loading of osteocytes.MLO-Y4 osteocytes were pre-incubated with IL-1 beta (0.1-1 ng/ml) for 24 h. Cells were either or not subjected to mechanical loading by 1 h pulsating fluid flow (PFF: 0.7 +/- 0.3 Pa, 5 Hz) in the presence of IL-1 beta (0.1-1 ng/ml). Conditioned medium was collected after 1 h PFF or static cultures. Subsequently mouse bone marrow cells were seeded on top of the IL-1 beta-treated osteocytes to determine osteoclastogenesis. Conditioned medium from mechanically loaded or static IL-1 beta-treated osteocytes was added to co-cultures of untreated osteocytes and mouse bone marrow cells. Gene expression of cysteine-rich protein 61 (CYR61/CCN1), receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) by osteocytes was determined immediately after PFF.Incubation of osteocytes with IL-1 beta, as well as conditioned medium from static 1L-1 beta-treated osteocytes increased the formation of osteoclasts. However, conditioned medium from mechanically loaded IL-1 beta-treated osteocytes prevented osteoclast formation. Incubation with IL-1 beta upregulated RANKL and down-regulated OPG gene expression by static osteocytes. PFF upregulated CYR61, RANKL, and OPG gene expression by osteocytes.Our results suggest that IL-1 beta increases osteocyte-modulated osteoclastogenesis, and that mechanical loading of osteocytes may abolish IL-1 beta-induced osteoclastogenesis. (C) 2012 Elsevier Inc. All rights reserved.