Osteocytic Pericellular Matrix (PCM): Accelerated Degradation under In Vivo Loading and Unloading Conditions Using a Novel Imaging Approach.
Osteocytic Pericellular Matrix (PCM): Accelerated Degradation under In Vivo Loading and Unloading Conditions Using a Novel Imaging Approach.
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DOI：
10.3390/genes13010072
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发表时间：
2021-12-28
期刊：
影响因子：
3.5
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Pei S;Wang S;Martinez JR;Parajuli A;Kirn-Safran CB;Farach-Carson MC;Lu XL;Wang L
骨细胞是骨组织中数量最多的细胞，其周围细胞基质（PCM）控制着骨细胞的生物物理和生物化学微环境。作为一种分子筛，骨细胞PCM不仅调节骨细胞的物质运输，而且还作为外部机械环境的传感器。由于技术挑战，骨细胞PCM的周转率在很大程度上仍然未知。在这里，我们报告了一种新的成像技术的基础上代谢标记和“点击化学”，标记从头PCM周围的骨细胞在体外和体内的“晕”。然后，我们测试了这种方法，并在年轻人与老年人的骨骼中显示了不同的标记模式。进一步的“脉冲追踪”实验显示，培养骨细胞的PCM的“半衰期”（~70 h）与体内骨细胞的PCM的“半衰期”（~75 d）存在显著差异。当小鼠经受3周后肢卸载或7周胫骨加载（5.1N，4 Hz，3d/周）时，PCM半衰期缩短（~20 d）并且降解加速。基质金属肽酶MMP-14在机械负载的骨细胞中升高，这可能有助于PCM降解。这项研究提供了一个详细的程序，使半定量研究骨细胞PCM重塑在体内和体外。
The proteoglycan-containing pericellular matrix (PCM) controls both the biophysical and biochemical microenvironment of osteocytes, which are the most abundant cells embedded and dispersed in bones. As a molecular sieve, osteocytic PCMs not only regulate mass transport to and from osteocytes but also act as sensors of external mechanical environments. The turnover of osteocytic PCM remains largely unknown due to technical challenges. Here, we report a novel imaging technique based on metabolic labeling and “click-chemistry,” which labels de novo PCM as “halos” surrounding osteocytes in vitro and in vivo. We then tested the method and showed different labeling patterns in young vs. old bones. Further “pulse-chase” experiments revealed dramatic difference in the “half-life” of PCM of cultured osteocytes (~70 h) and that of osteocytes in vivo (~75 d). When mice were subjected to either 3-week hindlimb unloading or 7-week tibial loading (5.1 N, 4 Hz, 3 d/week), PCM half-life was shortened (~20 d) and degradation accelerated. Matrix metallopeptidase MMP-14 was elevated in mechanically loaded osteocytes, which may contribute to PCM degradation. This study provides a detailed procedure that enables semi-quantitative study of the osteocytic PCM remodeling in vivo and in vitro.
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影响因子：
3.1
作者：
Klein-Nulend, J.;Bacabac, R. G.;Bakker, A. D.
通讯作者：
Bakker, A. D.
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影响因子：
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通讯作者：
Duncan, Randall L.
影响因子：
6.9
作者：
Farach-Carson, Mary C.;Warren, Curtis R.;Harrington, Daniel A.;Carson, Daniel D.
通讯作者：
Carson, Daniel D.
影响因子：
4.1
作者：
Kelly, Natalie H.;Schimenti, John C.;van der Meulen, Marjolein C. H.
通讯作者：
van der Meulen, Marjolein C. H.
影响因子：
2.5
作者：
Kostrominova, Tatiana Y.
通讯作者：
Kostrominova, Tatiana Y.