Smoking Alters Inflammation and Skeletal Stem and Progenitor Cell Activity During Fracture Healing in Different Murine Strains.
Smoking Alters Inflammation and Skeletal Stem and Progenitor Cell Activity During Fracture Healing in Different Murine Strains.
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DOI：
10.1002/jbmr.4175
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发表时间：
2021-01
影响因子：
6.2
通讯作者：
Lee, Francis Y.
中科院分区：
文献类型：
--
作者：
Hao, Zichen;Li, Jun;Li, Bo;Alder, Kareme D.;Cahill, Sean, V;Munger, Alana M.;Lee, Inkyu;Kwon, Hyuk-Kwon;Back, JungHo;Xu, Shuogui;Kang, Min-Jong;Lee, Francis Y.
关键词：
吸烟者骨折修复后延迟愈合或不愈合的风险更高。很少有具体的干预措施可用于预防，因为导致这些负面后遗症的分子机制知之甚少。模拟吸烟者骨折愈合的小鼠模型对于进一步了解吸烟引起的骨折愈合过程中局部细胞和分子的变化至关重要。我们将三种小鼠品系C57 BL/6 J、129 X1/SvJ和BALB/cJ暴露于香烟烟雾中3个月，然后诱导股骨中段横截骨术。我们在截骨术后4周使用X线摄影、微计算机断层扫描（μCT）和生物力学测试评估骨折愈合情况。放射学分析表明吸烟129 X1/SvJ小鼠的骨折愈合能力显著降低。μCT结果显示，香烟烟雾暴露后，所有三种菌株的骨折骨痂延迟重塑。生物力学测试表明，与C57 BL/6 J和BALB/cJ小鼠相比，香烟烟雾暴露后，129 X1/SvJ的功能特性的最显着的损害。因此，129 X1/SvJ应变最适合于模拟吸烟引起的骨折愈合受损。此外，在吸烟129 X1/SvJ小鼠模型中，我们使用组织学、流式细胞术和多重细胞因子/趋化因子分析研究了吸烟引起的骨折愈合的分子和细胞变化。组织学分析显示吸烟导致软骨形成受损。此外，重要的修复性细胞群，包括骨骼干细胞及其下游祖细胞，表现出吸烟导致的损伤后扩增减少。此外，在吸烟小鼠中证实了骨折血肿中促炎介质和免疫细胞的募集显著增加。总的来说，我们的研究结果表明，吸烟损害骨折愈合过程中的细胞和分子的显着变化，包括破坏软骨形成，异常的骨骼干细胞和祖细胞活性，以及明显的初始炎症反应。© 2020美国骨与矿物质研究学会（ASBMR）。
Smokers are at a higher risk of delayed union or nonunion after fracture repair. Few specific interventions are available for prevention because the molecular mechanisms that result in these negative sequelae are poorly understood. Murine models that mimic fracture healing in smokers are crucial in further understanding the local cellular and molecular alterations during fracture healing caused by smoking. We exposed three murine strains, C57BL/6J, 129X1/SvJ, and BALB/cJ, to cigarette smoke for 3 months before the induction of a midshaft transverse femoral osteotomy. We evaluated fracture healing 4 weeks after the osteotomy using radiography, microcomputed tomography (μCT), and biomechanical testing. Radiographic analysis demonstrated a significant decrease in the fracture healing capacity of smoking 129X1/SvJ mice. μCT results showed delayed remodeling of fracture calluses in all three strains after cigarette smoke exposure. Biomechanical testing indicated the most significant impairment in the functional properties of 129X1/SvJ in comparison with C57BL/6J and BALB/cJ mice after cigarette smoke exposure. Thus, the 129X1/SvJ strain is most suitable in simulating smoking-induced impaired fracture healing. Furthermore, in smoking 129X1/SvJ murine models, we investigated the molecular and cellular alterations in fracture healing caused by cigarette smoking using histology, flow cytometry, and multiplex cytokine/chemokine analysis. Histological analysis showed impaired chondrogenesis in cigarette smoking. In addition, the important reparative cell populations, including skeletal stem cells and their downstream progenitors, demonstrated decreased expansion after injury as a result of cigarette smoking. Moreover, significantly increased pro-inflammatory mediators and the recruitment of immune cells in fracture hematomas were demonstrated in smoking mice. Collectively, our findings demonstrate the significant cellular and molecular alterations during fracture healing impaired by smoking, including disrupted chondrogenesis, aberrant skeletal stem and progenitor cell activity, and a pronounced initial inflammatory response. © 2020 American Society for Bone and Mineral Research (ASBMR).
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影响因子：
3.8
作者：
Camlin, Nicole J.;McLaughlin, Eileen A.;Holt, Janet E.
通讯作者：
Holt, Janet E.
DOI：
10.11138/mltj/2013.3.2.063
发表时间：
2013-04-01
期刊：
Muscles, ligaments and tendons journal
影响因子：
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作者：
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Salini, Vincenzo
DOI：
10.1152/ajplung.00389.2017
发表时间：
2018-11-01
影响因子：
4.9
作者：
Glynos, Constantinos;Bibli, Sofia-Iris;Papapetropoulos, Andreas
通讯作者：
Papapetropoulos, Andreas
影响因子：
5.3
作者：
Fiset, Sandra;Godbout, Charles;Schemitsch, Emil H.
通讯作者：
Schemitsch, Emil H.
DOI：
10.1038/nrrheum.2014.164
发表时间：
2015-01
期刊：
Nature reviews. Rheumatology
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