Role of subchondral bone properties and changes in development of load-induced osteoarthritis in mice.

Role of subchondral bone properties and changes in development of load-induced osteoarthritis in mice.
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软骨下骨特性及变化在小鼠负荷诱导性骨关节炎发生发展中的作用

DOI:
10.1016/j.joca.2017.08.016
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发表时间:
2017-12
影响因子:
7
通讯作者:
van der Meulen MCH
van der Meulen MCH
中科院分区:
医学2区
文献类型:
--
作者:
Adebayo OO;Ko FC;Wan PT;Goldring SR;Goldring MB;Wright TM;van der Meulen MCH

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创伤后骨关节炎(OA)的动物模型表明,软骨下骨(SCB)的性质和重塑可能在疾病的发生和发展中发挥重要作用。因此,我们研究了SCB属性的作用及其对负荷诱导的OA进展的影响,通过应用胫骨负荷模型对两种不同的小鼠品系阿仑膦酸钠(ALN)治疗。对26周龄雄性C57B1/6(B6,低骨量)和FVB(高骨量)小鼠的左胫骨施加循环压缩。小鼠用ALN(26 μ g/kg/天)或溶媒(VEH)处理1、2或6周的负荷持续时间。采用组织学和显微计算机断层扫描分析关节软骨、软骨下骨和骺松质骨的变化。与B6小鼠相比,FVB小鼠表现出更厚的软骨、更厚的SCB板、以及更高的骨骺松质骨质量和组织矿物质密度。负荷诱导软骨病理学、骨赘形成和SCB变化;然而,与FVB小鼠相比,B6小鼠中较低的初始SCB质量和刚度并未减轻负荷诱导的OA严重程度。相比之下,FVB小鼠表现出较少的软骨损伤,生长较慢且不太成熟的骨赘。在B6小鼠中,通过ALN治疗抑制骨重建加重了6周负荷后的软骨病理学,而在FVB小鼠中,抑制骨重建保护肢体免受负荷诱导的软骨损失。内在较低的SCB属性与衰减的负荷诱导的软骨损失无关。然而,抑制骨重建在具有低SCB性质的动物中产生了OA病理学的差异模式,表明这些因素确实影响负荷诱导的OA进展。
Animal models recapitulating post-traumatic osteoarthritis (OA) suggest that subchondral bone (SCB) properties and remodeling may play major roles in disease initiation and progression. Thus, we investigated the role of SCB properties and its effects on load-induced OA progression by applying a tibial loading model on two distinct mouse strains treated with alendronate (ALN). Cyclic compression was applied to the left tibia of 26-week-old male C57Bl/6 (B6, low bone mass) and FVB (high bone mass) mice. Mice were treated with ALN (26μg/kg/day) or vehicle (VEH) for loading durations of 1, 2, or 6 weeks. Changes in articular cartilage and subchondral and epiphyseal cancellous bone were analyzed using histology and microcomputed tomography. FVB mice exhibited thicker cartilage, a thicker SCB plate, and higher epiphyseal cancellous bone mass and tissue mineral density than B6 mice. Loading induced cartilage pathology, osteophyte formation, and SCB changes; however, lower initial SCB mass and stiffness in B6 mice did not attenuate load-induced OA severity compared to FVB mice. In contrast, FVB mice exhibited less cartilage damage, and slower-growing and less mature osteophytes. In B6 mice, inhibiting bone remodeling via ALN treatment exacerbated cartilage pathology after 6 weeks of loading, while in FVB mice, inhibiting bone remodeling protected limbs from load-induced cartilage loss. Intrinsically lower SCB properties were not associated with attenuated load-induced cartilage loss. However, inhibiting bone remodeling produced differential patterns of OA pathology in animals with low compared to high SCB properties, indicating that these factors do influence load-induced OA progression.
DOI: 10.1002/art.23176
发表时间: 2008-01-01
影响因子: --
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DOI: 10.1002/jor.23204
发表时间: 2016-11
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影响因子: --
作者:
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