Callus mineralization and maturation are delayed during fracture healing in interleukin-6 knockout mice
Callus mineralization and maturation are delayed during fracture healing in interleukin-6 knockout mice
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DOI：
10.1016/j.bone.2007.07.022
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发表时间：
2007-12-01
期刊：
影响因子：
4.1
通讯作者：
Bostrom, Mathias P. G.
中科院分区：
文献类型：
--
作者：
Yang, Xu;Ricciardi, Benjamin F.;Bostrom, Mathias P. G.
IL-6是一种参与肌肉骨骼系统细胞信号传导的多效性细胞因子，但其在骨愈合中的作用仍不确定。本研究的目的是检查IL-6在骨折愈合中的作用。对八周龄雄性C57 BL/6和IL-6 -/-小鼠的右侧股骨进行横向、中段骨干截骨术。处死时间点为骨折后1、2、4或6周（每组N = 14）。通过显微计算机断层扫描（micro-CT）和傅里叶变换红外成像光谱（FT-IRIS）分析愈伤组织的性质。组织学上测量软骨和胶原含量以及破骨细胞密度。在完整的未骨折骨中，与野生型小鼠相比，IL-6 -/-小鼠的结晶度矿物质/基质比、组织矿物质密度（TMD）和骨体积分数（BVF）降低。这表明在IL-6 -/-小鼠中存在基线骨质量的潜在缺陷。骨折后2周，IL-6 -/-小鼠的骨痂结晶度和矿物质/基质比降低。这些变化在4周时不太明显。在2周时，与野生型小鼠中的这些参数相比，IL-6 -/-小鼠的愈伤组织具有增加的组织矿物质密度（TMD）、增加的软骨和胶原含量以及减少的破骨细胞密度。到第4周和第6周，两种小鼠品系之间的这些参数不再有差异。总之，与野生型小鼠的愈伤组织相比，IL-6 -/-小鼠具有延迟的愈伤组织成熟、矿化和重塑。这些作用是短暂的，表明IL-6的作用似乎在骨折愈合的早期阶段是最重要的。(C)2007年爱思唯尔公司All rights reserved.
IL-6 is a pleiotropic cytokine involved in cell signaling in the musculoskeletal system, but its role in bone healing remains uncertain. The purpose of this study was to examine the role of IL-6 in fracture healing. Eight-week-old male C57BL/6 and IL-6 -/- mice were subjected to transverse, mid-diaphyseal osteotomies on the right femora. Sacrifice time points were 1, 2, 4, or 6 weeks post-fracture (N = 14 per group). Callus tissue properties was analyzed by microcomputed tomography (micro-CT) and Fourier transform infrared imaging spectroscopy (FT-IRIS). Cartilage and collagen content, and osteoclast density were measured histologically. In intact unfractured bone, IL-6 -/- mice had reduced crystallinity mineral/matrix ratio, tissue mineral density (TMD), and bone volume fraction (BVF) compared to wildtype mice. This suggests that there was an underlying deficit in baseline bone quality in IL-6 -/- mice. At 2 weeks post-fracture, the callus of IL-6 -/- mice had reduced crystallinity and mineral/matrix ratio. These changes were less evident at 4 weeks. At 2 weeks, the callus of the IL-6 -/- mice had an increased tissue mineral density (TMD), an increased cartilage and collagen content, and reduced osteoclast density compared to these parameters in wildtype mice. By 4 and 6 weeks, these parameters were no longer different between the two strains of mice. In conclusion, IL-6 -/- mice had delayed callus maturity, mineralization, and remodeling compared with the callus of the wildtype mice. These effects were transient indicating that the role of IL-6 appears to be most important in the early stages of fracture healing. (C) 2007 Elsevier Inc. All rights reserved.