Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery M81, Copenhagen University Hospitals - Bispebjerg and Frederiksberg, 11 Nielsine Nielsensvej, DK-2400 Copenhagen, Denmark; Center for Healthy Aging, Department of Clinical Medicine, University of Copenhagen, 3B Blegdamsvej, DK-2200 Copenhagen, Denmark.
Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery M81, Copenhagen University Hospitals - Bispebjerg and Frederiksberg, 11 Nielsine Nielsensvej, DK-2400 Copenhagen, Denmark; Center for Healthy Aging, Department of Clinical Medicine, University of Copenhagen, 3B Blegdamsvej, DK-2200 Copenhagen, Denmark.
Osteoarthritis Cartilage. 2022 Jun;30(6):886-895. doi: 10.1016/j.joca.2022.03.007. Epub 2022 Mar 28.
Cartilage collagen has very limited repair potential, though some turnover and incorporation has not been fully excluded. We aim to determine the regional turnover of human osteoarthritis cartilage.
Patients scheduled for knee joint replacement surgery due to osteoarthritis were recruited in this prospective study of four weeks duration. Deuterium oxide (DO) was administered orally by weekly boluses at 70% DO, initially 150 ml followed by three boluses of 50 ml. Cartilage from the medial tibia plateau was sampled centrally, under the meniscus, and from osteophytes and treated enzymatically with hyaluronidase and trypsin. Samples were analysed for deuterium incorporation in alanine using mass spectrometry and for gene expression by real-time reverse transcriptase polymerase chain reaction.
Twenty participants completed the study: mean (SD) age 64 ± 9.1 years, 45% female, BMI 29.5 ± 4.8 kg/m. Enzymatically treated cartilage from central and submeniscal regions showed similar enrichments at 0.063% APE, while osteophytes showed significantly greater enrichment at 0.072% APE (95% confidence interval of difference) [0.004-0.015]). Fractional synthesis rates were similar for central 0.027%/day and submeniscal cartilage 0.022%/day but 10-fold higher in osteophytes 0.22%/day [0.098-0.363]. When compared to central cartilage, submeniscal cartilage had increased gene expression of MMP-3 and decreased lubricin expression. Untreated cartilage had higher turnover (enrichments at 0.073% APE) than enzymatically treated cartilage (0.063% APE).
In OA, despite regional differences in gene expression, the turnover of the articular cartilage matrix across the entire joint surface is very limited, but higher turnover was observed in osteophyte cartilage.
尽管软骨胶原的修复潜力非常有限，但仍不能完全排除其存在一定的代谢和更新。本研究旨在确定人骨性关节炎软骨的区域性代谢情况。
本前瞻性研究为期四周，共纳入 20 名因骨性关节炎行膝关节置换术的患者。患者每周口服一次重水（DO），初始剂量为 150ml，DO 浓度为 70%，随后分三次给予 50ml 的 DO 剂量。于关节镜下获取内侧胫骨平台的软骨样本，包括半月板下区域、骨赘部位，并使用透明质酸酶和胰蛋白酶进行酶解处理。采用质谱法分析丙氨酸中的氘掺入情况，采用实时逆转录聚合酶链反应分析基因表达情况。
20 名参与者完成了本研究：平均（标准差）年龄 64±9.1 岁，女性占 45%，BMI 为 29.5±4.8kg/m2。中央和半月板下软骨的酶解处理样本的富集度相似，均为 0.063% APE，而骨赘的富集度显著更高，为 0.072% APE（95%置信区间差值）[0.004-0.015]）。中央软骨的合成速率为 0.027%/天，半月板下软骨的合成速率为 0.022%/天，而骨赘的合成速率则高达 0.22%/天[0.098-0.363]。与中央软骨相比，半月板下软骨的 MMP-3 基因表达增加，而润滑素表达减少。未经酶解处理的软骨的周转率（APE 为 0.073%）高于酶解处理的软骨（APE 为 0.063%）。
在 OA 中，尽管关节表面不同区域的基因表达存在差异，但整个关节表面的关节软骨基质的代谢非常有限，但在骨赘软骨中观察到更高的周转率。
