Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO, USA.
Department of Cell Biology and Physiology, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO, USA.
Cartilage. 2020 Oct;11(4):458-472. doi: 10.1177/1947603518796122. Epub 2018 Sep 3.
To query the transcript-level changes in the medial and lateral tibial plateau cartilage in tandem with obesity in patients with end-stage osteoarthritis (OA).
Cartilage was obtained from 23 patients (20 obese [body mass index > 30 kg/m], 3 overweight [body mass index < 30 kg/m]) at the time of total knee replacement. Cartilage integrity was assessed using Outerbridge scale, while radiographic changes were scored on preoperative X-rays using Kellgren-Lawrence (K-L) classification. RNA was probed for differentially expressed transcripts between medial and lateral compartments using Affymetrix Gene 2.0 ST Array and validated via real-time polymerase chain reaction. Gene ontology and pathway analyses were also queried.
Scoring of cartilage integrity by the Outerbridge scale indicated that the medial and lateral compartments were similar, while scoring by the K-L classification indicated that the medial compartment was more severely damaged than the lateral compartment. We observed a distinct transcript profile with >50% of transcripts unique between medial and lateral compartments. and were more highly expressed in medial versus lateral compartment. Polymerase chain reaction confirmed expression of 4 differentially expressed transcripts. Numerous transcripts, biological processes, and pathways were significantly different between overweight and obese patients with a differential response of obesity on medial and lateral compartments.
Our findings support molecular differences between medial and lateral compartments reflective of the greater severity of OA in the medial compartment. The K-L system better reflected the molecular results than did the Outerbridge. Moreover, the molecular effect of obesity was different between the medial and lateral compartments of the same knee plausibly reflecting the molecular effects of differential biomechanical loading.
探究肥胖与膝骨关节炎（OA）终末期患者内外侧胫骨平台软骨的转录水平变化。
在全膝关节置换时，从 23 名患者（20 名肥胖者[体重指数>30kg/m]，3 名超重者[体重指数<30kg/m]）中获取软骨。采用 Outerbridge 量表评估软骨完整性，术前 X 线片采用 Kellgren-Lawrence（K-L）分级评估放射学变化。采用 Affymetrix Gene 2.0 ST 阵列对内侧和外侧隔间之间差异表达的转录本进行探查，并通过实时聚合酶链反应进行验证。还进行了基因本体和途径分析。
Outerbridge 量表对软骨完整性的评分表明内侧和外侧隔间相似，而 K-L 分级的评分表明内侧隔间比外侧隔间受损更严重。我们观察到一个明显的转录谱，其中>50%的转录本在内侧和外侧隔间之间是独特的。和在与外侧隔间相比，在内侧隔间中表达更高。聚合酶链反应证实了 4 个差异表达转录本的表达。超重和肥胖患者之间有许多转录本、生物过程和途径存在显著差异，肥胖对内侧和外侧隔间的反应也不同。
我们的发现支持了内侧和外侧隔间之间的分子差异，反映了内侧隔间 OA 的严重程度更高。K-L 系统比 Outerbridge 更能反映分子结果。此外，同一膝关节内外侧隔间的肥胖的分子效应不同，这可能反映了不同生物力学负荷的分子效应。
