Reduced bone loss in a murine model of postmenopausal osteoporosis lacking complement component 3.
Reduced bone loss in a murine model of postmenopausal osteoporosis lacking complement component 3.
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DOI：
10.1002/jor.23643
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Dennis JE
中科院分区：
文献类型：
--
作者：
MacKay DL;Kean TJ;Bernardi KG;Haeberle HS;Ambrose CG;Lin F;Dennis JE
骨免疫学领域的不断发展，旨在解开骨骼和免疫系统之间复杂的相互依赖关系。值得注意的是，我们和其他人已经证明，补体信号影响成骨细胞和破骨细胞的分化，这两种主要细胞类型负责维持骨稳态。然而，补体对体内骨稳态的净效应尚不清楚。我们已发表的体外机制研究使我们假设，在绝经后骨质疏松症的基于卵巢切除术的模型中，补体激活级联反应中的中心蛋白补体成分3（C3）的缺失可防止骨丢失。事实上，我们在这里报告说，与C57 BL/6 J（WT）小鼠相比，卵巢切除C3缺陷小鼠在多个部位的骨丢失减少，股骨颈的硬度增加，后者可能改善机械功能。WT和B6; 129 S4-C3 tm 1Crr/J（C3−/−）小鼠在6周龄时进行卵巢切除或假手术，并在12周龄时实施安乐死。采集骨骼的MicroCT显示，切除卵巢的C3−/−小鼠股骨近端和远端干骺端的骨小梁体积分数显著大于WT小鼠。腰椎表现出显着更大的类骨质含量和矿物质沉积率。力学测试表明，卵巢切除的C3−/−小鼠股骨颈的刚度显著增加。这些结果表明，C3缺乏减少了卵巢切除术时的骨丢失，并可能改善机械性能。从C57 BL/6 J（WT）和B6; 129 S4-C3 tm 1Crr/J（C3−/−）小鼠采集的骨骼的MicroCT显示，切除卵巢的C3−/−小鼠的近端胫骨和远端股骨干骺端中的骨小梁体积分数显著大于其WT对应小鼠。他们的腰椎显示出明显更高的类骨质含量和矿物质沉积率，力学测试表明股骨颈的刚度明显更大。这些结果表明，C3缺乏减少卵巢切除术引起的骨丢失，并可能改善机械性能。
The growing field of osteoimmunology seeks to unravel the complex interdependence of the skeletal and immune systems. Notably, we and others have demonstrated that complement signaling influences the differentiation of osteoblasts and osteoclasts, the two primary cell types responsible for maintaining bone homeostasis. However, the net effect of complement on bone homeostasis in vivo was unknown. Our published in vitro mechanistic work led us to hypothesize that absence of complement component 3 (C3), a central protein in the complement activation cascade, protects against bone loss in the ovariectomy-based model of postmenopausal osteoporosis. Indeed, we report here that, when compared to their C57BL/6J (WT) counterparts, ovariectomized C3 deficient mice experienced reduced bone loss at multiple sites and increased stiffness at the femoral neck, the latter potentially improving mechanical function. WT and B6;129S4‐C3tm1Crr/J (C3−/−) mice were either ovariectomized or sham-operated at 6 weeks of age and euthanized at 12 weeks. MicroCT on harvested bones revealed that the trabecular bone volume fraction in the metaphyses of both the proximal tibiae and distal femora of ovariectomized C3−/− mice is significantly greater than that of their WT counterparts. Lumbar vertebrae showed significantly greater osteoid content and mineral apposition rates. Mechanical testing demonstrated significantly greater stiffness in the femoral necks of ovariectomized C3−/− mice. These results demonstrate that C3 deficiency reduces bone loss at ovariectomy and may improve mechanical properties. MicroCT on bones harvested from C57BL/6J (WT) and B6;129S4‐C3tm1Crr/J (C3−/−) mice revealed that the trabecular bone volume fraction in the metaphyses of both the proximal tibiae and distal femora of ovariectomized C3−/− mice is significantly greater than that of their WT counterparts. Their lumbar vertebrae showed significantly greater osteoid content and mineral apposition rates, and mechanical testing demonstrated significantly greater stiffness at the femoral neck. These results demonstrate that C3 deficiency reduces ovariectomy-induced bone loss and may improve mechanical properties.
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影响因子：
4.4
作者：
Mathieu, MC;Sawyer, N;Therien, AG
通讯作者：
Therien, AG
影响因子：
25.7
作者：
Bykov, Igor;Jauhiainen, Matti;Meri, Seppo
通讯作者：
Meri, Seppo
DOI：
10.1016/b978-0-12-416015-6.00004-6
发表时间：
2014-01-01
期刊：
BASIC AND APPLIED BONE BIOLOGY
影响因子：
--
作者：
Allen, Matthew R.;Burr, David B.
通讯作者：
Burr, David B.
影响因子：
3.7
作者：
Andrades, JA;Nimni, ME;Sorgente, N
通讯作者：
Sorgente, N
影响因子：
6.2
作者：
ERIKSEN, EF;HODGSON, SF;RIGGS, BL
通讯作者：
RIGGS, BL