Roemhildt M L, Beynnon B D, Gardner-Morse M, Anderson K, Badger G J
McClure Musculoskeletal Research Center, Department of Orthopedics and Rehabilitation, College of Medicine, University of Vermont, Burlington, VT 05405, USA.
J Biomech Eng. 2012 Oct;134(10):104501. doi: 10.1115/1.4007453.
This study describes the first application of a varus loading device (VLD) to the rat hind limb to study the role of sustained altered compressive loading and its relationship to the initiation of degenerative changes to the tibio-femoral joint. The VLD applies decreased compressive load to the lateral compartment and increased compressive load to the medial compartment of the tibio-femoral joint in a controlled manner. Mature rats were randomized into one of three groups: unoperated control, 0% (sham), or 80% body weight (BW). Devices were attached to an animal's leg to deliver altered loads of 0% and 80% BW to the experimental knee for 12 weeks. Compartment-specific material properties of the tibial cartilage and subchondral bone were determined using indentation tests. Articular cartilage, calcified cartilage, and subchondral bone thicknesses, articular cartilage cellularity, and degeneration score were determined histologically. Joint tissues were sensitive to 12 weeks of decreased compressive loading in the lateral compartment with articular cartilage thickness decreased in the peripheral region, subchondral bone thickness increased, and cellularity of the midline region decreased in the 80% BW group as compared to the 0% BW group. The medial compartment revealed trends for diminished cellularity and aggregate modulus with increased loading. The rat-VLD model provides a new system to evaluate altered quantified levels of chronic in vivo loading without disruption of the joint capsule while maintaining full use of the knee. These results reveal a greater sensitivity of tissue parameters to decreased loading versus increased loading of 80% BW for 12 weeks in the rat. This model will allow future mechanistic studies that focus on the initiation and progression of degenerative changes with increased exposure in both magnitude and time to altered compressive loads.
本研究描述了首次将内翻加载装置（VLD）应用于大鼠后肢，以研究持续改变的压缩负荷的作用及其与胫股关节退变起始的关系。VLD以可控方式降低胫股关节外侧间室的压缩负荷，并增加内侧间室的压缩负荷。成年大鼠被随机分为三组之一：未手术对照组、0%（假手术）或80%体重（BW）组。将装置连接到动物腿部，对实验膝关节施加0%和80%BW的改变负荷，持续12周。使用压痕试验测定胫骨软骨和软骨下骨的特定间室材料特性。通过组织学方法测定关节软骨、钙化软骨和软骨下骨厚度、关节软骨细胞密度和退变评分。与0%BW组相比，80%BW组的关节组织对外侧间室12周的压缩负荷降低敏感，外周区域的关节软骨厚度减小，软骨下骨厚度增加，中线区域的细胞密度降低。内侧间室显示出随着负荷增加细胞密度和聚集模量降低的趋势。大鼠-VLD模型提供了一个新系统，用于评估体内慢性负荷改变的量化水平，而不破坏关节囊，同时保持膝关节的充分使用。这些结果表明，在大鼠中，与12周80%BW的负荷增加相比，组织参数对负荷降低更为敏感。该模型将有助于未来的机制研究，重点关注退变变化的起始和进展，随着暴露于改变的压缩负荷的幅度和时间增加。
