Metaphyseal and diaphyseal bone loss in the tibia following transient muscle paralysis are spatiotemporally distinct resorption events.
Metaphyseal and diaphyseal bone loss in the tibia following transient muscle paralysis are spatiotemporally distinct resorption events.
复制标题
DOI：
10.1016/j.bone.2013.09.009
复制
发表时间：
2013-12
期刊：
影响因子：
4.1
通讯作者：
Gross, Ted S.
中科院分区：
文献类型：
--
作者：
Ausk, Brandon J.;Huber, Philippe;Srinivasan, Sundar;Bain, Steven D.;Kwon, Ronald Y.;McNamara, Erin A.;Poliachik, Sandra L.;Sybrowsky, Christian L.;Gross, Ted S.
当骨骼受到分解代谢的挑战时，在松质骨和皮质骨部位观察到的骨吸收的时间和程度有很大的差异。目前尚不清楚这种通常在单个骨骼中明显的吸收异质性是由于特定部位对骨吸收的容许性增加，还是源于不同健壮性的局部性吸收事件。为了探讨这个问题，我们使用了小腿麻痹诱导的骨丢失的小鼠模型，这导致了不同时间和不同程度的干骺端和干端的骨吸收。鉴于这种表型的吸收模式，我们假设胫骨近端干骺端和骨干端的骨丢失是通过在空间和时间上不同的吸收事件发生的。为了验证这一假设，我们进行了三项免费的体内/μCT成像研究。具体地说，我们定义了小腿瘫痪后3周内皮质内骨吸收的时空变化，应用一种新的图像配准方法来确定胫骨近端干骺端的骨吸收起始位置，并使用基于μCT的骨吸收参数来探索不同的基础破骨细胞活动对干骺端骨丢失起始量的作用。在每项研究中都观察到干骺端和骨干端骨吸收的不同反应。肌肉麻痹后的急性皮质内骨丢失几乎完全发生在干骺端(6天内占全部皮质内骨丢失的96.5%)。使用我们的小梁图像配准方法，我们进一步解决了生长板附近具有显著基础破骨细胞功能的焦点区域(0.03mm3)的干骺端骨质丢失的起始问题。这种由基础生长板细胞动力学介导的瘫痪引起的骨丢失的相关性观察得到了5周龄小鼠与13个月龄小鼠的急性干骺端破骨反应的支持。具体地说，基于μCT的骨吸收速率归一化到初始骨小梁表面(BRRBS)，年轻组比老年组高3.7倍(2.27±0.27μm~3/μm~2/d比0.60±0.44μm~3/μm~2/d)。截瘫后第2周(81.3%的骨干骨皮质内扩张在第6~13天)，骨干端骨丢失开始于整个胫骨长轴(81.3%的骨干端皮质内扩张)，而不是聚焦于干骺端的骨丢失。其发生的时机和同质性与新生破骨细胞介导的骨干吸收是一致的。综上所述，我们的数据表明，由一过性小腿麻痹引起的胫骨干骺端和骨干端骨丢失在空间和时间上都是离散的事件。在更广泛的背景下，这些发现是澄清多个吸收事件的时间和来源的关键的第一步，这些事件需要靶向来完全抑制神经肌肉损伤后的骨丢失。
When the skeleton is catabolically challenged, there is great variability in the timing and extent of bone resorption observed at cancellous and cortical bone sites. It remains unclear whether this resorptive heterogeneity, which is often evident within a single bone, arises from increased permissiveness of specific sites to bone resorption or localized resorptive events of varied robustness. To explore this question, we used the mouse model of calf paralysis induced bone loss, which results in metaphyseal and diaphyseal bone resorption of different timing and magnitude. Given this phenotypic pattern of resorption, we hypothesized that bone loss in the proximal tibia metaphysis and diaphysis occurs through resorption events that are spatially and temporally distinct. To test this hypothesis, we undertook three complimentary in vivo/μCT imaging studies. Specifically, we defined spatiotemporal variations in endocortical bone resorption during the 3 weeks following calf paralysis, applied a novel image registration approach to determine the location where bone resorption initiates within the proximal tibia metaphysis, and explored the role of varied basal osteoclast activity on the magnitude of bone loss initiation in the metaphysis using μCT based bone resorption parameters. A differential response of metaphyseal and diaphyseal bone resorption was observed throughout each study. Acute endocortical bone loss following muscle paralysis occurred almost exclusively within the metaphyseal compartment (96.5% of total endocortical bone loss within 6 days). Using our trabecular image registration approach, we further resolved the initiation of metaphyseal bone loss to a focused region of significant basal osteoclast function (0.03 mm3) adjacent to the growth plate. This correlative observation of paralysis induced bone loss mediated by basal growth plate cell dynamics was supported by the acute metaphyseal osteoclastic response of 5-wk vs. 13- month-old mice. Specifically, μCT based bone resorption rates normalized to initial trabecular surface (BRRBS) was 3.7-fold greater in Young vs. Aged mice (2.27 ± 0.27 μm3/μm2/day vs. 0.60 ± 0.44 μm3/μm2/day). In contrast with the focused bone loss initiation in the metaphysis, diaphyseal bone loss initiated homogeneously throughout the long axis of the tibia predominantly in the second week following paralysis (81.3% of diaphyseal endocortical expansion between days 6 and 13). The timing and homogenous nature is consistent with de novo osteoclastogenesis mediating the diaphyseal resorption. Taken together, our data suggests that tibial metaphyseal and diaphyseal bone loss induced by transient calf paralysis are spatially and temporally discrete events. In a broader context, these findings are an essential first step toward clarifying the timing and origins of multiple resorptive events that would require targeting to fully inhibit bone loss following neuromuscular trauma.
登录
查看更多内容
影响因子：
3.8
作者：
Boyd, Steven K.;Moser, Stephan;Gasser, Juerg S.
通讯作者：
Gasser, Juerg S.
影响因子：
4.8
作者：
GLOBUS, RK;BIKLE, DD;MOREYHOLTON, E
通讯作者：
MOREYHOLTON, E
影响因子：
6.2
作者：
Han, ZH;Palnitkar, S;Parfitt, AM
通讯作者：
Parfitt, AM
影响因子：
3.3
作者：
Hefferan, TE;Evans, GL;Turner, RT
通讯作者：
Turner, RT
影响因子：
4.1
作者：
Li, Wenjun;Kezele, Irina;Lang, Thomas
通讯作者：
Lang, Thomas