Pucha Krishna A, McKinney Jay M, Fuller Julia M, Willett Nick J
Research Service, VA Medical Center, Decatur, GA, USA.
Department of Orthopedics, Emory University, Atlanta, GA, USA.
Osteoarthr Cartil Open. 2020 Apr 18;2(3):100066. doi: 10.1016/j.ocarto.2020.100066. eCollection 2020 Sep.
Osteoarthritis (OA) is a chronic degenerative disease of the joints characterized by articular cartilage degradation. While clear sex differences exist in human OA development, most pre-clinical research has been conducted solely in male animals, limiting generalizability of findings to both sexes. The objective of this study was to determine if sex impacts the progression and severity of OA in the rat medial meniscal tear (MMT) preclinical model used to surgically induce OA. It was hypothesized that differences would be observed between males and females following MMT surgery.
An MMT model was employed in male and female Lewis rats to induce OA. Animals were euthanized 3 weeks post-surgery and EPIC-μCT was used to quantitatively evaluate articular cartilage structure and composition, osteophyte volumes and subchondral bone structure.
Analysis of medial 1/3 articular cartilage, showed increased cartilage thickness and proteoglycan loss in the MMT of both sexes, when compared to sham. Both male and female MMT groups also saw increased subchondral bone mineral density and larger osteophyte volumes. Significant interactions between sex and OA development were seen in normalized cartilage volume (larger in females), and normalized total osteophyte volumes (larger in males).
This study demonstrates the viability of both sexes in the rat MMT preclinical OA model. Though clear differences exist, this model can be used to model OA development and evaluate sex as a factor in the efficacy of OA therapeutics.
骨关节炎(OA)是一种以关节软骨退变为特征的慢性退行性疾病。虽然人类OA的发展存在明显的性别差异,但大多数临床前研究仅在雄性动物中进行,限制了研究结果对两性的普遍适用性。本研究的目的是确定性别是否会影响用于手术诱导OA的大鼠内侧半月板撕裂(MMT)临床前模型中OA的进展和严重程度。假设在MMT手术后,雄性和雌性之间会观察到差异。
在雄性和雌性Lewis大鼠中采用MMT模型诱导OA。术后3周对动物实施安乐死,并使用EPIC-μCT定量评估关节软骨的结构和组成、骨赘体积和软骨下骨结构。
对内侧1/3关节软骨的分析显示,与假手术组相比,两性MMT组的软骨厚度增加且蛋白聚糖丢失。雄性和雌性MMT组的软骨下骨矿物质密度也增加,骨赘体积更大。在标准化软骨体积(雌性更大)和标准化总骨赘体积(雄性更大)方面,观察到性别与OA发展之间存在显著相互作用。
本研究证明了大鼠MMT临床前OA模型中两性的可行性。尽管存在明显差异,但该模型可用于模拟OA的发展,并将性别作为评估OA治疗效果的一个因素。