Lai-Zhao Y, Pitchers K K, Appleton C T
Department of Medicine, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Canada.
Department of Physiology and Pharmacology, The University of Western Ontario, Canada.
Osteoarthritis Cartilage. 2021 Jul;29(7):1060-1070. doi: 10.1016/j.joca.2021.03.010. Epub 2021 Mar 21.
Osteoarthritis (OA) is a serious joint disease with no disease-modifying medical treatment. To develop treatments targeting synovium, we must improve our understanding of the effects of OA-related changes in synovial physiology on joint tissue outcomes. The aim of this study was to investigate the effects of synovial pathology due to post-traumatic OA (PTOA) on articular chondrocyte physiology.
We first developed and validated a novel joint tissue co-culture system to model the biological interactions between synovium and articular chondrocytes. Whole-joint synovial tissue from a surgical rat model of PTOA vs sham and surgical-naïve controls was placed into a co-culture system with adult primary articular chondrocytes (n = 4-5). The effects of PTOA synovium on chondrocyte anabolic, inflammatory, and catabolic gene expression and sulfated glycosaminoglycan (sGAG) secretion and aggrecan synthesis were tested, and results from early and later stages of PTOA development were compared.
Synovial injury by arthrotomy (sham surgery) alone decreased primary chondrocyte expression of genes including Col2a1 (0.36 ± 0.15-fold) and Acan (0.41 ± 0.28-fold). Early PTOA synovium rescued the suppression of Acan, induced increased sGAG secretion (3.94 ± 0.44 μg/mL vs surgery-naïve 2.41 ± 0.55 and sham 2.92 ± 0.73 μg/mL controls), and upregulated Mmp3 (3.73 ± 2.62-fold) and Prg4 (4.93 ± 4.29-fold). These effects were lost with later stage PTOA synovium.
Early PTOA synovium induces transient anabolic responses in articular chondrocytes rather than pro-inflammatory responses that would require inhibition. These results suggest that PTOA synovium plays at least a partially protective role and that loss of these protective effects may contribute to PTOA progression.
骨关节炎（OA）是一种严重的关节疾病，尚无改善病情的药物治疗方法。为了开发针对滑膜的治疗方法，我们必须更好地了解OA相关的滑膜生理变化对关节组织结局的影响。本研究的目的是调查创伤后骨关节炎（PTOA）引起的滑膜病理对关节软骨细胞生理的影响。
我们首先开发并验证了一种新型的关节组织共培养系统，以模拟滑膜与关节软骨细胞之间的生物学相互作用。将来自PTOA手术大鼠模型与假手术和未进行手术的对照的全关节滑膜组织放入与成年原代关节软骨细胞（n = 4-5）的共培养系统中。测试了PTOA滑膜对软骨细胞合成代谢、炎症和分解代谢基因表达以及硫酸化糖胺聚糖（sGAG）分泌和聚集蛋白聚糖合成的影响，并比较了PTOA发展早期和晚期的结果。
仅通过关节切开术（假手术）造成的滑膜损伤降低了包括Col2a1（0.36±0.15倍）和Acan（0.41±0.28倍）在内的原代软骨细胞基因表达。早期PTOA滑膜挽救了Acan的抑制作用，诱导sGAG分泌增加（3.94±0.44μg/mL，未进行手术的对照组为2.41±0.55μg/mL，假手术组为2.92±0.73μg/mL），并上调Mmp3（3.73±2.62倍）和Prg4（4.93±4.29倍）。这些作用在PTOA滑膜后期消失。
早期PTOA滑膜在关节软骨细胞中诱导短暂的合成代谢反应，而不是需要抑制的促炎反应。这些结果表明，PTOA滑膜至少起部分保护作用，而这些保护作用的丧失可能有助于PTOA的进展。
